A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PF-07817883 FOLLOWING ORAL ADMINISTRATION OF NEW FORMULATIONS RELATIVE TO THE REFERENCE FORMULATION IN HEALTHY ADULT PARTICIPANTS UNDER FASTED CONDITION
Phase: PHASE1
Conditions: Healthy
Sponsor: Pfizer

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1
Title P a ge
A P H A S E 1, O P E N -L A B E L, R A N D O M I Z E D, SI N G L E D O S E, C R O S S O V E R S T U D Y T O 
E S TI M A T E T H E R E L A TI V E BI O A V AI L A BI LI T Y O F P F -0 7 8 1 7 8 8 3 F O L L O WI N G 
O R A L  A D MI NI S T R A TI O N O F N E W F O R M U L A TI O N S R E L A TI V E T O T H E 
R E F E R E N C E F O R M U L A TI O N I N H E A L T H Y A D U L T P A R TI CI P A N T S U N D E R 
F A S T E D C O N DI TI O N
St u d y I nter ve nti o n N u m ber :
P F -0 7 8 1 7 8 8 3
St u d y I nter ve nti o n N a me:
N A
U S I N D N u m ber:
1 6 2 6 4 4
E U C T N u m ber:
2 0 2 3- 5 0 6 4 4 2- 2 4- 0 0
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 0 9 1 0 1 3
P h ase:
P hase 1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A st u d y  t o lear n h o w P F-0 7 8 1 7 8 8 3 is ta ke n u p i nt o t he bl o o d of healt h y 
a d ults after ta ki n g ta blets of st u d y  dr u g wit h var y i n g i n gre die 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 m e nt Hist or y
D oc u me nt
Versi o n D ate
Ori gi nal pr ot oc ol
2 4 A u g ust 2 0 2 3
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 .....................................................................................................................8
LI S T O F FI G U R E S ................................................................................................................... 8
1. P R O T O C O L  S U M M A R Y..................................................................................................... 9
1. 1. S y n o p sis .................................................................................................................... 9
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 8
2. 1. St u d y  Rati o nale....................................................................................................... 1 8
2. 2. Bac k gr o u n d ............................................................................................................. 1 8
2. 2. 1. Disease O ver vie w ....................................................................................... 1 8
2. 2. 2. Rati o nale f or De vel o p me nt of P F -0 7 8 1 7 8 8 3.............................................. 1 8
2. 2. 3. N o ncli nical O ver vie w ................................................................................. 1 9
2. 2. 4. Bi o p har mace utics a n d N o ncli nical P har mac o ki netics ................................ 1 9
2. 2. 4. 1. Bi o p har mace utics ...................................................................... 1 9
2. 2. 4. 2. N o ncli nical P har mac o ki netics a n d i n vitr o Meta b olis m ........... 1 9
2. 2. 5. T o xic ol o g y  of P F-0 7 8 1 7 8 8 3....................................................................... 2 0
2. 2. 6. Cli nical O ver vie w ....................................................................................... 2 1
2. 2. 6. 1. S u m mar y  of P F-0 7 8 1 7 8 8 3 P har mac o ki netics i n H u ma ns ........ 2 1
2. 2. 6. 2. Safet y O ver vie w ........................................................................ 2 2
2. 3. Be nefit/ Ris k Assess me nt ......................................................................................... 2 2
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 6
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
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 1. I ncl usi o n Criteria ..................................................................................................... 2 7
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, Alc o h ol, a n d T o bacc o ................................................................. 3 0
5. 3. 4. Acti vit y ....................................................................................................... 3 1
5. 4. Scree n Fail ures ........................................................................................................ 3 1
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 1
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 3
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................ 3 4
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. 5. St u d y  Int er 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
6. 9. 1. Resc ue Me dici ne ......................................................................................... 3 6
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. E C G C ha n ges ..............................................................................................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................................ ...............................4 0
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures ................................................................. 4 0
8. 1. 1. Baseli ne Pr oce d ures .................................................................................... 4 1
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 1. 1. 1. Me dical Hist or y ......................................................................... 4 1
8. 1. 1. 2. De m o gra p hics ............................................................................4 1
8. 2. Efficac y  Assess me nts..............................................................................................4 1
8. 3. Safet y Assess me nts ................................................................................................. 4 1
8. 3. 1. Vital Si g ns .................................................................................................. 4 1
8. 3. 1. 1. B l o o d Press ure a n d P ulse Rate.................................................. 4 1
8. 3. 2. P h y sical E xa mi nati o ns ................................................................................ 4 2
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 3
8. 3. 5. C O VI D -1 9 S pecific Assess me nts............................................................... 4 3
8. 3. 6. Pre g na nc y  Testi n g ...................................................................................... 4 4
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d O t her Safety Re p orti n g ................. 4 4
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 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 ................... 4 5
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es .......................................................... 4 6
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 1
8. 6. 1. S pecifie d Ge netics ...................................................................................... 5 1
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics ................................................... 5 1
8. 7. Bi o mar kers .............................................................................................................. 5 1
8. 8. I m m u n o ge nicit y Assess me nts ................................................................................. 5 1
8. 9. Healt h Ec o n o mics ................................................................................................... 5 1
8. 1 0. Dr u g Pr o d uct Acce pta bilit y  Q uesti o n naire ........................................................... 5 2
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 5 2
9. 1. Statistical H y p ot heses ............................................................................................. 5 2
9. 2. A nal y sis Sets ........................................................................................................... 5 2
9. 3. Statistical A nal y ses ................................................................................................. 5 2
9. 3. 1. Ge neral C o nsi derati o ns ............................................................................... 5 3
9. 3. 2. Pri mar y  E n d p oi nt(s) A nalys is..................................................................... 5 3
9. 3. 2. 1. Defi niti o n of E n d p oi nt(s) .......................................................... 5 3
9. 3. 2. 2. Mai n A nal yt ical A p pr oac h........................................................ 5 3
9. 3. 3. Sec o n dar y  E n d p oi nt(s) A nalys is................................................................. 5 4
9. 3. 4. Tertiar y / E x pl orat or y E n d p oi nt(s) A nalys is ................................................5 4
9. 3. 5. Safet y A nal ys es .......................................................................................... 5 4
9. 3. 5. 1. Electr ocar di o gra m A nal y ses...................................................... 5 5
9. 3. 6. Ot her A nal ys es ............................................................................................ 5 5
9. 4. I nteri m A nal ys es ..................................................................................................... 5 5
9. 5. Sa m ple Size Deter mi nati o n ..................................................................................... 5 5
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S .......................................................................................................... 5 7
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 7
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns .................................................... 5 7
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 7
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................5 8
1 0. 1. 3. Data Pr otecti o n ......................................................................................... 5 9
1 0. 1. 4. C o m mittees Str uct ure ............................................................................... 5 9
1 0. 1. 4. 1. Data M o nit ori n g C o m mittee ................................................... 5 9
1 0. 1. 5. Disse mi nati o n of Cli nical St u d y  Data ...................................................... 5 9
1 0. 1. 6. Data Q ualit y Ass ura nce ............................................................................ 6 0
1 0. 1. 7. S o urce D oc u me nts .................................................................................... 6 2
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 1. 8. Use of Me dical Rec or ds ............................................................................ 6 2
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................6 3
1 0. 1. 1 0. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual.............................................. 6 3
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests................................................................. 6 5
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 us i o n Criteria................................. 7 3
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................ 7 3
1 0. 4. 4. C o ntrace pti o n Met h o ds ............................................................................. 7 4
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 6
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 8
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 8
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 8
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 8
1 0. 6. 3. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ................................................................................................... 7 9
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 0
1 0. 8. A p pe n di x 8: Dr u g Pr o d uct Acce pta bilit y  Q uesti o n naire ......................................8 2
1 0. 9. A p pe n di x 9: A b bre viati o ns ................................................................................... 8 4
1 1. R E F E R E N C E S .................................................................................................................. 8 8
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
LI S T O F T A B L E S
Ta ble 1.
Sc he d ule of Acti vities ...............................................................................1 5
Ta ble 2.
St u d y  Desi g n............................................................................................. 2 5
Ta ble 3.
Plas ma P F - 0 7 8 1 7 8 8 3 P K Para meters Defi niti o ns.................................... 5 3
Ta ble 4.
E x pecte d Wi dt hs of t he 9 0 % CI s ( wit h 8 0 % C o vera ge Pr o ba bilit y) 
f or Differe nt P ossi ble Esti mate d Effects f or A U Ci nf, A U Clast, a n d 
C ma x ........................................................................................................... 5 6
Ta ble 5.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts............................................. 6 5
LI S T O F FI G U R E S
Fi g ure 1.
Sc he ma ...................................................................................................... 1 4
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: A P hase 1, O pe n -La bel, Ra n d o mize d, Si n gle D ose, Cr oss o ver St u d y  t o 
Esti mate the Relati ve Bi oa vaila bilit y  of PF -0 7 8 1 7 8 8 3 F oll o wi n g Oral A d mi nistrati o n o f Ne w 
F or m ulati o ns Relati ve t o T he Refere nce F or m ulati o n in Healt h y  A d ult Partici pa nts U n der 
Faste d C o n diti o n
Brief Title: A st u d y  t o lear n h o w P F -0 7 8 1 7 8 8 3 is ta ke n u p i nt o t he bl o o d of healt h y a d ults
after ta ki n g t a blets of st u d y dr u g wit h var y i n g i n gre die 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 6 2 6 4 4
E U C T N u m ber:
2 0 2 3 -5 0 6 4 4 2 -2 4 -0 0
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 0 9 1 0 1 3
P h ase:
P hase 1
R ati o n ale :
P F -0 7 8 1 7 8 8 3 is a p ote nt a n d selecti ve i n hi bit or of t he se vere ac ute res pirat or y sy n dr o me 
c or o na vir us 2 ( S A R S -C o V -2) mai n pr otease (M
pr o) t hat is c urre ntly bei n g de vel o pe d as a n 
oral treat me nt of c or o na vir us disease 2 0 1 9 ( C O VI D - 1 9).
T he p ur p ose of t his st u d y is t o esti mate t he oral bi oa vaila bilit y of 3 ne w f or m ulati o ns of 
P F -0 7 8 1 7 8 8 3 (test) relati ve t o refere nce ta blet f or m ulati o n i n healt h y a d ult partici pa nts u n der 
faste d c o n diti o ns. T he st u d y will als o assess t he safety a n d t olera bi lit y of test a n d refere nce 
ta blet f or m ulati o ns i n healt h y a d ult partici pa nts. 
Res ults fr o m t his st u d y  will i nf or m t he selecti o n of f or m ulati o n f or s u bse q ue nt st u dies i n t he 
de vel o p me nt pr o gra m .
O bjecti ves a n d E n d p oi nts :
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y: 

T o deter mi ne t he oral bi oa vaila bilit y of test oral
f or m ulati o ns of P F -0 7 8 1 7 8 8 3 relati ve t o the 
refere nce oral f or m ulati o n.

C ma x a n d A U C i nf if data per mit, ot her wise 
A U C last.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
P F -0 7 8 1 7 8 8 3 f or m ulati o ns i n healt h y partici pa nts.

Assess me nt of T E A E s, cli nical la b orat or y 
a b n or malities, vital si g ns, a n d 1 2 -lea d E C Gs.
A b bre viati o ns: A U C i nf=area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 e xtra p olate d t o i nfi nit y, 
A U C last=area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 t o t he ti me of t he last q ua ntifia ble 
c o nce ntrati o n, C ma x = ma xi m u m o bser ve d c o nce ntrati o n, E C G =electr ocar di o gra m, T E A E =treat me nt e mer ge nt 
a d verse e ve nt.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
O ver all Desi g n :
T his is a P hase 1, o pe n -la bel, ra n d o mize d, 4 -peri o d, 4 -se q ue nce cr oss o ver st u d y i n healt hy 
a d ult partici pa nts e val uati n g t he oral bi oa vaila bilit y of 3 ne w P F -0 7 8 1 7 8 8 3 test oral 
f or m ulati o n(s) c o m pare d t o P F-0 7 8 1 7 8 8 3 refere nce oral f or m ulati o n .
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 i n or der t o ha ve at least 
8 c o m pleters .
N ote: “E nr olle d ” mea ns a partici pa nt ’s, or t heir le gally a ut h orize d re prese ntati ve’s, 
a gree me nt t o partici pate i n a cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess a n d ra n d o mizati o n t o st u d y i nter ve nti o n.
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 
Part ici pa nts m ust meet t he f oll o wi n g ke y i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
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 heal t h y as 
deter mi ne d b y me dical e val uati o n i ncl u di n g me dical hist or y, p h ys ical e xa mi nati o n, 
la b orat or y tests, a n d E C G .
2.
B o d y mass i n de x ( B MI ) of 1 6 t o 3 2 k g/ m 2; a n d a t otal b o d y wei g ht >4 5 k g .
3.
Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt 
pla n, la b orat or y  tests, lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt.
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
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 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my). 

Hist or y  of 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 g e 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, la b orat or y a b n or mality, or ot her c o n diti o ns a n d sit uati o ns 
that 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.
P ositi ve test res ult f or S A R S -C o V -2 i nfecti o n at a d missi o n.
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of m o derate/str o n g C Y P 3 A i n d ucers or ti me-
de pe n de nt i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da 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.
5.
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 stu d y  ( w hic he ver is l o n ger).
6.
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) f or partici pa nts < 6 0 years; a n d ≥1 5 0/ 9 0 m m/ H g f or partici pa nts ≥6 0 ye ars 
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.
7.
Sta n dar d 1 2 -lea d E C G (si n gle) t hat de m o nstrates cli nicall y rele va nt a b n or malities 
t hat ma y affect partici pa nt safety or i nter pretati o n of st u d y res ults (e g, Q T c 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 -se g me nt 
a n d T- wa ve [S T - T] i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d - or 
t hir d- de gree atri o ve ntric ular [A V ] bl oc k, or seri o us bra d yarr h yt h mias or 
tac hyarr h yt h mias). If Q Tc F e xcee ds 4 5 0 ms , or a c o m bi nati o n of t hree of t he 
gra p hical deflecti o ns see n o n a t y pical electr ocar di o gra m (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 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
deter mi ne t he partici pa nt’s eli gi bilit y . C o m p uter-i nter prete d E C Gs s h o ul d be 
o verrea d b y a p h ys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt.
8.
Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
Scree ni n g, as assesse d b y 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: 

As partate a mi n otra nsferase ( A S T ) or ala ni ne a mi n otra nsferase (A L T ) le vel 
> 1. 5 × u p per li mit of n or mal (U L N );

T otal bilir u bi n le vel ≥1. 5 × U L N; partici pa nts wit h a hist or y  of Gil bert's 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤U L N.
9.
Hist or y  of alc o h ol a b use or bi n ge dri n ki n g a n d/ or a n y ot her illicit dr u g use or 
de pe n de nce wit hi n 6 m o nt hs of Scree ni n g. Bi n ge dri n ki n g is defi ne d as a patte r n of 
5 ( male) a n d 4 (fe male) or m ore alc o h olic dri n ks i n a b o ut 2 h o urs. As a ge neral r ule, 
alc o h ol i nta ke s h o ul d n ot e xcee d 1 4 u nits per wee k ( 1 u nit = 8 o u nces ( 2 4 0 m L ) beer, 
1 o u nce ( 3 0 m L ) of 4 0 % s pirit, or 3 o u nces ( 9 0 m L ) of wi ne).
1 0. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers. 
St u d y Ar ms a n d D ur ati o n:
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 7 8 1 7 8 8 3
Use
E x peri me ntal
I M P or NI M P/ A x M P
I M P
D ose F or m ul ati o n
All test f or m ulati o ns a n d t he refere nce f or m ulati o n are i m me diate release ta blets a n d 
e x pecte d ha ve si milar perf or ma nce . All ta blet f or m ulati o ns are of 3 0 0 m g u nit stre n gt h.
U nit D ose Stre n gt h(s)
3 0 0 m g/ta blet
R o ute of A d mi nistr ati o n
Oral
A b bre viati o ns: A x M P = a u xiliar y me dici nal pr o d uct, I M P = i n vesti gati o nal me dici nal pr o d uct, NI M P = n o n -
i n vesti gati o nal me dici nal pr o d uct.\
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
St u d y Ar m(s)
Ar m Title
A
B
C
D
Ar m Descri pti o n
Partici pa nts will 
recei ve 3 00 m g S D
of refere nce 
f or m ulati o n o n Da y 1 
of t he treat me nt 
peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D 
of test f or m ulati o n 1 
o n Da y 1 of t he 
treat me nt peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D 
of test f or m ulati o n 2 
o n Da y 1 of t he 
treat me nt peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D of 
test f or m ulati o n 3 o n 
Da y 1 of t he treat me nt 
peri o d
A b bre viati o n: S D =si n gle d ose.
St atistic al Met h o ds :
A sa m ple size of a p pr o xi matel y  1 2 partici pa nts wit h 8 c o m pleters was c h ose n t o pr o vi de 
a de q uate precisi o n t o c o m pare t he relati ve bi oa vaila bilit y  of test f or m ulati o ns of 
P F -0 7 8 1 7 8 8 3 relati ve t o t he refere nce f or m ulati o n i n Peri o ds 1 t hr o u g h 4 .
F or t he pri mar y  o bjecti ve, nat ural l o g tra nsf or me d A U C i nf (if data per mit), A U C last
( ot her wise), an d C ma x f or P F- 0 7 8 1 7 8 8 3 will be a nal y ze d usi n g a mi xe d effect m o del wit h 
se q ue nce, peri o d a n d treat me nt as fi xe d effects a n d partici pa nt wit hi n se q ue nce as a ra n d o m 
effect i n Peri o ds 1 t o 4. Esti mates of t he a dj uste d mea n differe nces ( test-refere nce) a n d 
c orres p o n di n g 9 0 % c o nfi de nce i nter vals will be o btai ne d fr o m t he m o del. T he a dj uste d mea n 
differe nces a n d 9 0 % c o nfi de nce i nter vals f or t he differe nces will be e x p o ne nt iate d t o pr o vi de 
esti mates of t he rati o of a dj uste d ge o metric mea ns ( test/refere nce) a n d 9 0 % c o nfi de nce 
i nter vals f or t he rati os. Treat me nt A will be t he Refere nce treat me nt w hile Treat me nts B, C, 
a n d D will be t he test treat me nts. 
All safet y a nal ys es will be perf or me d o n t he safety p o p ulati o n. A d verse e ve nts ( A Es ), E C Gs, 
vital si g ns , 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 safet y of partici pa nts. A n y cli nical la b orat or y, E C G, a n d vital 
si g n 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. P las ma p har mac o ki netic ( P K ) para meters t o be s u m marize d descri pti vel y.
Et hic al C o nsi der ati o ns:
P F -0 7 8 1 7 8 8 3 is n ot e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y partici pa nts. T his 
st u d y is desi g ne d pri maril y t o ge nerate P K, safety a n d t olera bilit y data f or f urt her cli nical 
de vel o p me nt.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Fi g ure 1 .
Sc he m a
D MI D, l ot n u m bers :
A: D P -0 0 6 0 6 7, 2 3- D P -0 1 4 4 9
B: D P -0 0 6 0 6 7, 2 3- D P -0 1 5 2 6
C: D P -0 0 6 9 7 3, 2 3- D P -0 1 6 8 7
D: D P - 0 0 6 9 7 4, 2 3-D P -0 1 6 9 6
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 hed ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d in t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well -bei n g of t he partici pa nt .
T a ble 1.
Sc he d ule of Acti vities
Visit I de ntifier 
A b bre vi ati o ns use d i n 
t his t a ble m a y be f o u n d 
i n Secti o n 1 0. 9
Scree ni n g
F or e ac h of Peri o d 1 - 4
F U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 t o 
D a y - 2
D a y 
- 1
D a y 1
D a y 2
D a y 3
2 8 -
3 5 
d a ys

F/ U acti vities o nl y i n t he last peri o d.

F/ U ma y occ ur via tele p h o ne c o ntact,
m ust occ ur 2 8 - 3 5 da ys after t he fi nal 
d ose of st u d y i nter ve nti o n.

Da y -1 acti vities o nl y bef ore Peri o d 1 
Da y 1.
Pl a n ne d h o urs P ost d ose
0
0. 5
1
2
4
6
8
1 2
2 4
4 8
I nf or me d c o nse nt
X
I ncl usi o n/e xcl usi o n 
criteria
X  
X

Peri o d 1 o nl y
C R U C o nfi ne me nt
X
 
 
 



 
 

X
Me dical/ me dicati o n 
hist or y ( u p date)
X  
X
De m o gra p h y (i ncl u di n g 
wei g ht a n d hei g ht)
X

Refer t o Secti o n 8. 1. 1. 2
C o ntrace pti o n c hec k
X  
X
X  
X  
X

Da y 3 perf or me d o nl y at disc har ge fr o m 
C R U
1 2 ‑lea d E C G (si n gle)
X
X
X
X

Da y 1 perf or me d pre -d ose

Da y 1 n o t re q uire d i n Peri o ds 2- 4

Da y 3 o nl y i n last peri o d
Vital si g ns ( B P/ P R)
X
X
X
X

Da y 1 perf or me d pre -d ose

Da y 3 o nl y i n t he last peri o d

Refer t o Secti o n 8. 3. 1
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 1.
Sc he d ule of Acti vities
Visit I de ntifier 
A b bre vi ati o ns use d i n 
t his t a ble m a y be f o u n d 
i n Secti o n 1 0. 9
Scree ni n g
F or e ac h of Peri o d 1 - 4
F U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 t o 
D a y - 2
D a y 
- 1
D a y 1
D a y 2
D a y 3
2 8 -
3 5 
d a ys

F/ U acti vities o nl y i n t he last peri o d.

F/ U ma y occ ur via tele p h o ne c o ntact,
m ust occ ur 2 8 - 3 5 da ys after t he fi nal 
d ose of st u d y i nter ve nti o n.

Da y -1 acti vities o nl y bef ore Peri o d 1 
Da y 1.
Pl a n ne d h o urs P ost d ose
0
0. 5
1
2
4
6
8
1 2
2 4
4 8
C O VI D -1 9 test / 
pr oce d ures
X  
X

C O VI D -1 9 test t o meet i ncl usi o n o n 
a d missi o n . Ot her C O VI D-1 9 relate d 
pr oce d ure s per l ocal re g ulati o ns.
P E
X  
X
X

P E  will be perf or me d at scree ni n g or 
a d missi o n .

P E at E T visit o nl y at PI’s discreti o n
Seri o us a n d n o nseri o us 
A E m o nit ori n g
X
 
 
 
 



 
 
 

X  
X
Uri ne sa m ple f or :
Uri ne dr u g testi n g
X  
X

N ot re q uire d i n Peri o d s 2 -4
Uri nal ysis
X  
X
X
X

Da y 3 i n last peri o d o nl y
Bl o o d sa m p le f or: 
Safet y la b orat or y 
(≥4 h fasti n g)
X  
X
X
X

Da y 3 i n last peri o d o nl y.
Ser u m F S H ( p ost -
me n o pa usal fe males o nl y)
X
Pre g na nc y test ( W O C B P 
o nl y)
X  
X
X
X

Da y 3 perf or me d o nl y at disc har ge fr o m 
t he C R U.
Ser ol o g y: H Bs A g, 
H Bs A b, H Bc A b, H C V A b, 
a n d HI V
X
P K plas ma sa mpli n g f or 
P F ‑ 0 7 8 1 7 8 8 3
X  
X  
X  
X  
X  
X
X  
X  
X  
X
X

T he sa m ple at 0 h will be t he pre -d ose P K 
sa m ple.

4 8 h P K sa m ple i n Peri o d s 1 t o 3 will be 
c o nsi dere d 0 h P K sa m ple f or t he 
s u bse q ue nt peri o d.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 1.
Sc he d ule of Acti vities
Visit I de ntifier 
A b bre vi ati o ns use d i n 
t his t a ble m a y be f o u n d 
i n Secti o n 1 0. 9
Scree ni n g
F or e ac h of Peri o d 1 - 4
F U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 t o 
D a y - 2
D a y 
- 1
D a y 1
D a y 2
D a y 3
2 8 -
3 5 
d a ys

F/ U acti vities o nl y i n t he last peri o d.

F/ U ma y occ ur via tele p h o ne c o ntact,
m ust occ ur 2 8 - 3 5 da ys after t he fi nal 
d ose of st u d y i nter ve nti o n.

Da y -1 acti vities o nl y bef ore Peri o d 1 
Da y 1.
Pl a n ne d h o urs P ost d ose
0
0. 5
1
2
4
6
8
1 2
2 4
4 8
A d mi nistrati o n of st u d y i nter ve nti o n :
P F -0 7 8 1 7 8 8 3 d osi n g
X

See Secti o n 5. 3. 2 Meals a n d Dietar y 
Restricti o ns
Ot her assess me nt s:
Dr u g pr o d uct acce pta bilit y 
Q uesti o n naire
X

T he assess me nt will be a d mi nistere d 
i m me diatel y after t he d ose i n eac h peri o d
(see A p pe n di x 8 ).
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. I N T R O D U C TI O N
P F -0 7 8 1 7 8 8 3 is a p ote nt a n d selecti ve i n hi bit or of t he S A R S-C o V - 2 mai n pr otease ( Mp r o), 
t hat is bei n g de vel o pe d as a n oral treat me nt i n patie nts wit h C O VI D -1 9. 
2. 1. St u d y R ati o n ale 
T he p ur p ose of t his st u d y is t o esti mate t he oral bi oa vaila bilit y of 3 ne w ta blet f or m ulati o ns
of P F -0 7 8 1 7 8 8 3 (test) relati ve t o refere nce ta blet f or m ulati o n i n healt h y a d ult partici pa nts
u n der faste d c o n diti o n s. T he st u d y  will als o assess t he safet y a n d t olera bilit y, of test a n d 
refere nce ta blet f or m ulati o ns i n healt h y a d ult partici pa nts. A d diti o nall y , dr u g pr o d uct 
acce pta bilit y will be e x pl ore d f or eac h of t he f or m ulati o ns.
Res ults fr o m t his st u d y  will i nf or m t he selecti o n of f or m ulati o n f or s u bse q ue nt st u dies i n t he 
de vel o p me nt pr o gra m.
2. 2. B ac k gr o u n d 
2. 2. 1. Dise ase O ver vie w
I n Dece m ber 2 0 1 9, C O VI D-1 9 was i de ntifie d as a ne w, p ote ntiall y  fatal, res pirat or y i nfecti o n 
ca use d b y t he n o vel c or o na vir us S A R S -C o V -2. T he W H O declare d C O VI D - 1 9 a P u blic 
Healt h E mer ge nc y  of I nter nati o nal C o ncer n o n 2 0 Ja n uar y 2 0 2 0 a n d f urt her c haracterize d t he 
disease o ut brea k as a pa n de mic o n 1 1 Marc h 2 0 2 0. 1
C O VI D - 1 9 ma nif ests as a wi de ra n ge of ill nesses, fr o m asy m pt o matic i nfecti o n t o se vere 
p ne u m o nia, A R D S, a n d deat h. W hile t he maj orit y of cases (a p pr o xi matel y  8 0 %) are 
as ym pt o matic or mil d, 2 patie nts w h o are h os pitalize d wit h C O VI D -1 9 ma y  e x perie nce 
si g nifica nt m or bi dity a n d m ortalit y 3 ,4 a n d are at i ncrease d ris k of de vel o pi n g c o m or bi dities 
s uc h as A R D S, ac ute car diac i nj ur y, t hr o m b oe m b olic e ve nts, a n d/ or ki d ne y i nj ur y.5 -7
2. 2. 2. R ati o n ale f or De vel o p me nt of P F - 0 7 8 1 7 8 8 3
T he c or o na vir us M pr o is a virall y-e nc o de d e nz yme t hat is critical t o t he S A R S -C o V - 2 
re plicati o n c ycle, a nal o g o us t o ot her o bli gat or y  virall y-e nc o de d pr oteases (e g, HI V pr otease 
or H C V pr otease). M uta ge nesis e x peri me nts wit h ot her c or o na vir uses a n d pic or na vir uses t hat 
are relate d t o S A R S -C o V -2 ( pic or na vir us -li ke s u percl uster) ha ve de m o nstrate d t hat t he 
acti vit y of Mpr o is esse ntial f or viral re plicati o n. N o cl ose h u ma n a nal o gs of c or o na vir us Mpr o
e nz ymes are k n o w n, s u g gesti n g t hat a p pr o priate M pr o i n hi bit ors ma y f u ncti o n as selecti ve 
i n hi bit ors of S A R S-C o V -2 a n d ot her c or o na vir uses a s t hera pe utic a ge nts.
I n hi biti o n of t he S A R S-C o V - 2 Mpr o b y  nir matrel vir/rit o na vir has de m o nstrate d t he efficac y 
of a n a nti viral i n t he re d ucti o n of h os pitalizati o n a n d deat h i n mil d t o m o derate C O VI D - 1 9 
patie nts wit h hi g h ris k of pr o gressi o n t o se vere dise ase. Des pite t he a vaila bilit y  of 
n ir matrel vir/rit o na vir so me hi g h -ris k patie nts ma y be i neli gi ble f or nir matrel vir/rit o na vir d ue 
t o D DIs, a n d re m desi vir ma y be i naccessi ble f or s o me patie nts as it re q uires IV 
a d mi nistrati o n i n a healt hcare setti n g a n d ret ur ni n g f or t hree s u bse q ue nt da ys f or a d diti o nal 
dail y  IV d osi n g. T here re mai ns a n i m p orta nt nee d f or a d diti o nal safe a n d effecti ve 
t hera pe utic i nter ve nti o ns t hat d o n ot re q uire a d mi nistrati o n i n a healt hcare setti n g, are n ot 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
li mite d b y D DIs, a n d ha ve a ris k/ be nefit pr ofile s u p p orti ve of a d mi nistrati o n t o a br oa der 
patie nt p o p ulati o n.
2. 2. 3. N o ncli nic al O ver vie w
P F -0 7 8 1 7 8 8 3 is a p ote nt (I C 5 0 =  
µ M; K i =  
µ M) a n d selecti ve i n hi bit or of 
S A R S -C o V - 2 Mpr o, e x hi biti n g br oa d s pectr u m i n hi bit or y acti vity ac r oss t he C or o na viri dae 
fa mil y of Mpr o e nz ymes. T he i n vitr o a nti viral acti vit y  of P F-0 7 8 1 7 8 8 3 a gai nst S A R S -C o V - 2 
was de m o nstrate d i n se veral cell li nes. I n all cell ular s y ste ms teste d, P F-0 7 8 1 7 8 8 3 
de m o nstrate d p ote nt a nti viral acti vit y  a gai nst S A R S-C o V - 2. P F -0 7 8 1 7 8 8 3 als o e x hi bite d 
a nti viral efficac y a gai nst S A R S-C o V -1, H C o V -2 2 9 E, a n d M E R S -C o V i n cell ular s y ste ms. 
 
 
M ore details are prese nte d i n t he c urre nt I B.
2. 2. 4. Bi o p h ar m ace utics a n d N o ncli nic al P h ar m ac o ki netics 
2. 2. 4. 1. Bi o p h ar m ace utics
P F -0 7 8 1 7 8 8 3 is a ne utral c o m p o u n d e x hi biti n g m o derate a q ue o us a p pare nt s ol u bilit y  i n 
vari o us bi o -rele va nt me dia a n d l o w passi ve per mea bilit y. I n a preli mi nar y passi ve 
per mea bilit y  assess me nt i n t he R R C K cell li ne, P F-0 7 8 1 7 8 8 3 e x hi bite d a n A -B P a p p of 
0. 5 0 × 1 0 -6 c m/s, i n dicati n g l o w passi ve per mea bilit y . 
2. 2. 4. 2. N o ncli nic al P h ar m ac o ki netics a n d i n vitr o Met a b olis m
P F -0 7 8 1 7 8 8 3 e x hi bite d l o w i n vitr o per mea bilit y  a n d prefere ntially dist ri b ute d i nt o plas ma 
relati ve t o bl o o d cells. P F - 0 7 8 1 7 8 8 3 e x hi bite d a l o w t o m o derate C L, wit h a m o derate t o l o w 
V ss res ulti n g i n t½ val ues of a p pr o xi matel y  1 0 h o urs i n rats a n d 2. 8 h o urs i n m o n ke ys. 
F oll o wi n g oral d osi n g, P F- 0 7 8 1 7 8 8 3 was ra pi dl y a bs or be d wit h m o derate bi oa vaila bilit y i n 
rats a n d m o n ke ys. I n rat a n d m o n ke y re peat d ose t o xicit y st u dies, mea n sys te mic e x p os ures 
i ncrease d wit h i ncreasi n g d ose a n d n o c o nsiste nt se x-relate d differe nces were o bser ve d.
C o nce ntrati o n -de pe n de nt plas ma pr otei n bi n di n g was o bser ve d i n ra b bits a n d m o n ke y s, 
w hile n o mea ni n gf ul c o nce ntrati o n-de pe n de nt bi n di n g was o bser ve d i n h u ma ns at ≤1 0 µ M 
(
). P F- 0 7 8 1 7 8 8 3 distri b ute d i nt o t he li ver a n d 
l u n g t o a greater e xte nt t ha n ot her tiss ues, w hile distri b uti o n i nt o t he brai n was li mite d. 
 
C Y P -me diate d o xi dati o n was t he pri mar y meta b olic r o ute of P F -0 7 8 1 7 8 8 3 i n vitr o a n d i n 
rats. I n vitr o st u dies i n h u ma n li ver micr os o mes i n dicate d meta b olis m of P F-0 7 8 1 7 8 8 3 was 
pre d o mi na ntl y  me diate d b y C Y P 3 A 4 (
). 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
I n acc or da nce wit h F D A a n d E M A D DI g ui da nce, 
 
 
 
 
 
M ore details are prese nte d i n t he c urre nt I B.
2. 2. 5. T o xic ol o g y of P F- 0 7 8 1 7 8 8 3
P F - 0 7 8 1 7 8 8 3 was assesse d i n a series of n o ncli nical st u dies. 
T he t o xicit y  of P F-0 7 8 1 7 8 8 3 was e val uate d i n
G L P t o xicit y  
st u dies
 T here were 
n o a d verse fi n di n gs i n a n y of t he st u dies. T he N O A E L s i n t he 
 st u dies 
 
I n ge neral, t he n o n- a d verse fi n di n gs i n t he n o n G L P e x pl orat or y  st u dies a n d t he G LP pi v otal 
st u dies were si milar.
 
 
 
I n e m br yo- fetal de vel o p me nt st u dies, P F-0 7 8 1 7 8 8 3 was orall y a d mi nistere d d uri n g 
or ga n o ge nesis t o pre g na nt rats a n d ra b bits at d oses of 1 0 0, 3 0 0, or 1 0 0 0 m g/ k g / da y o n G D 
6- 1 7 (rats) or G D 7 -1 9 (ra b bits). I n t he rat, t here were n o P F - 0 7 8 1 7 8 8 3-relate d effects u p t o 
t he hi g hest d ose of 1 0 0 0 m g/ k g/ da y. U n b o u n d s ys te mic e x p os ures at t he N O A E L 
( 1 0 0 0 m g/ k g/ da y ) i n t his st u d y were 5 9 8 μ g• h/ m L a n d 9 2. 6 μ g/ m L f or A U C 2 4 a n d C ma x , 
res pecti vely. I n t he ra b bit, t here was n o P F -0 7 8 1 7 8 8 3 -relate d effect o n fetal m or p h ol o g y or 
e m br yo- fetal via bilit y u p t o t he hi g hest d ose of 1 0 0 0 m g/ k g/ da y. H o we ver, l o wer fetal b o d y 
wei g hts were o bser ve d at 1 0 0 0 m g/ k g/ da y  i n t he prese nce of n o n-a d verse effects o n mater nal 
b o d y  wei g ht a n d f o o d c o ns u m pti o n, res ulti n g i n a de vel o p me ntal N O A E L of 3 0 0 m g/ k g/ da y. 
U n b o u n d s y ste mic e x p os ures at 3 0 0 m g / k g/ da y i n t his st u d y were 1 4 5 μ g• h/ m L a n d 
4 4 μ g/ m L  f or A U C2 4 a n d C ma x , res pecti vely. I n t he c o m bi ne d ma le/fe male fertilit y st u d y i n 
Wistar Ha n rats, t here were n o P F - 0 7 8 1 7 8 8 3-relate d effects u p t o t he hi g hest d ose of 
1 0 0 0 m g/ k g/ da y .
M ore details are prese nte d i n t he c urre nt I B.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 2. 6. Cli nic al O ver vie w
As of t he date of t his pr ot oc ol , P F -0 7 8 1 7 8 8 3 is bei n g e val uate d i n 3 P hase 1 st u dies
( C 5 0 9 1 0 0 1, C 5 0 9 1 0 0 8 a n d C 5 0 9 1 0 1 4) a n d 1 P h ase 2 st u dy ( C 5 0 9 1 0 0 3) i n C O VI D-1 9 
patie nts . 
T he o n g oi n g st u d y C 5 0 9 1 0 0 1 is a m ulti part st u d y  i n healt h y a d ult partici pa nts t o e val uate t he 
safety, t olera bilit y a n d P K of P F - 0 7 8 1 7 8 8 3. P K of P F -0 7 8 1 7 8 8 3 was e val uate d i n 
P A R T -1: S A D, P A R T -2: M A D, P A R T -4: M E a n d P A R T -5: D DI  of a n o n g oi n g C 5 0 9 1 0 0 1 
st u d y. P A R T-5: D DI e val uate d t he effect of P F -0 7 8 1 7 8 8 3 o n mi daz ola m P K. I n a d diti o n, P K 
of P F -0 7 8 1 7 8 8 3 i n Ja pa nese a n d n o n -Ja pa nese p o p ulati o n was c o m pare d i n P A R T-5: D DI . 
T he d oses ra n ge d bet wee n 1 5 0- 4 0 0 0 m g a n d 2 0 0 -1 5 0 0 m g i n S A D a n d M A D, res pecti vel y. 
I n M A D stea dy state P F -0 7 8 1 7 8 8 3 P K was e val uate d after 1 0 da y s of BI D d osi n g. I n 
P A R T -4 : M E 6 0 0 m g P F -0 7 8 1 7 8 8 3 S D was a d mi nistere d t o healt h y a d ult partici pa nt s. 
P A R T - 5 e val uate d t he effect of re peat d osi n g of P F -0 7 8 1 7 8 8 3 o n t he P K of S D mi daz ola m . 
I n P A R T-6, effect of s u prat hera pe utic e x p os ures o n safet y, t olera bilit y, a n d Q Tc is bei n g 
assesse d at a n oral d ose of 6 0 0 0 m g ( gi ve n as 2 d oses of 3 0 0 0 m g at 0 a n d 1 hr).
C 5 0 9 1 0 0 8 is a n o n g oi n g P hase 1, o pe n -la bel, 2 peri o d, fix e d se q ue nce st u d y t o esti mate t he 
effect of itrac o naz ole (a str o n g C Y P 3 A 4 i n hi bit or) o n t he P K of P F -0 7 8 1 7 8 8 3 i n healt h y  
partici pa nts . St u dy C 5 0 9 1 0 1 4 will e val uat e t he effect of he patic i m pair me nt o n t he si n gle 
d ose P K of P F - 0 7 8 1 7 8 8 3, res pecti vely.
T he details of desi g n, o bjecti ves a n d e n d p oi nts are detaile d i n t he c urre nt I B.
2. 2. 6. 1. S u m m ar y of P F -0 7 8 1 7 8 8 3 P h ar m ac o ki netics i n H u m a ns
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
F urt her details o n t he cli nical P K of P F -0 7 8 1 7 8 8 3 are pr o vi de d i n t he c urre nt I B.
2. 2. 6. 2. S afet y O ver vie w
T he preli mi nar y  data c ollecte d i n St u d y C 5 0 9 1 0 0 1, as of t he data s na ps h ot ( 1 8 Ja n uar y  2 0 2 3) 
i n P A R T-1 a n d P A R T -2 of t he P hase 1 st u d y ( C 5 0 9 1 0 0 1) , de m o nstrate d a n acce pta ble safet y 
pr ofile at S Ds of P F -0 7 8 1 7 8 8 3 or place b o ra n gi n g fr o m 1 5 0 m g t o 4 0 0 0 m g i n P A R T -1, a n d 
at d oses of 2 0 0 m g  t o 1 5 0 0 m g BI D of PF- 0 7 8 1 7 8 8 3 or place b o f or 1 0 da y s i n P A R T- 2.
D ose escalati o n st o p pi n g r ules were n ot tri g gere d a n d M T D was n ot ac hie ve d. T here ha ve 
bee n n o deat hs, S A Es or S U S A Rs re p orte d. 
 
Preli mi nar y  res ults fr o m P A R T-6 s h o w acce pta ble safet y a n d t olera bilit y of 
P F - 0 7 8 1 7 8 8 3 i n healt hy a d ult v ol u nteers at t he d ose of 6 0 0 0 m g. Acc or di n g t o p reli mi nar y 
safety res ults fr o m C 5 0 9 1 0 0 8 ; a t otal of 1 2 healt h y a d ults were e nr olle d a n d c o m plete d t he 
st u d y. A t otal of 1 1 a d verse e ve nts occ urre d i n 4 partici pa nts, all of w hic h were mil d.
 
F urt her details o n t he cli nical safet y of P F - 0 7 8 1 7 8 8 3 are pr o vi de d i n t he c urre nt I B.
2. 3. Be nefit/ Ris k Assess me nt
P F -0 7 8 1 7 8 8 3 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 he 
p ur p ose of t his st u d y  is t o esti mate t he r B A of P F- 0 7 8 1 7 8 8 3 i n 3 t o 4 test ta blet f or m ulati o ns 
relati ve t o refere nce ta blet f or m ulati o n i n h ealt h y a d ult partici pa nts u n der faste d c o n diti o n .
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefit s a n d ris ks a n d reas o na bly 
e x pecte d A Es of P F-0 7 8 1 7 8 8 3 ma y  be f o u n d i n t he c urre nt 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 I nter 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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) P F -0 7 8 1 7 8 8 3 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 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
P F -0 7 8 1 7 8 8 3 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 P F-0 7 8 1 7 8 8 3 are j ustifie d b y  t he a ntici pate d be nefits t hat ma y 
be aff or de d t o partici pa nts wit h C O VI D- 1 9 i n f ut ure.
3. O B J E C TI V E S A N D E N D P O I N T S
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y: 

T o deter mi ne t he oral bi oa vaila bilit y of test oral
f or m ulati o ns of P F -0 7 8 1 7 8 8 3 relati ve t o the 
refere nce oral f or m ulati o n.

C ma x a n d A U C i nf if data per mit, ot her wise 
A U C last.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
P F -0 7 8 1 7 8 8 3 f or m ulati o ns i n healt h y partici pa nts.

Assess me nt of T E A E s, cli nical la b orat or y 
a b n or malities, vital si g ns, a n d 1 2 -lea d E C Gs.
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y: 

T o c haracterize t he P K of P F -0 7 8 1 7 8 8 3 after si n gle 
oral d ose of P F -0 7 8 1 7 8 8 3 f or m ulati o ns. 

Plas ma P K para meters: T ma x , C1 2, a n d if data 
per mit V z/ F, C L/ F a n d t½ .

T o assess t he dr u g pr o d uct acce pta bilit y of 
P F -0 7 8 1 7 8 8 3 f or m ulati o ns.

Assess me nt of dr u g pr o d uct acce pta bilit y via 
a q uesti o n naire.
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a P hase 1, o pe n -la bel, ra n d o mize d, 4- peri o d, 4 -se q ue nce cr oss o ver st u d y i n healt hy 
a d ult partici pa nts e val uati n g t he r B A of 3 ne w P F - 0 7 8 1 7 8 8 3 test oral f or m ulati o n(s) 
c o m pare d t o P F -0 7 8 1 7 8 8 3 refere nce oral f or m ulati o n . A p pr o xi matel y  1 2 partici pa nts will be 
e nr olle d i n t his st u d y wit h a p pr o xi matel y e q ual n u m ber of partici pa nts ra n d o mize d t o 1 of 4 
se q ue nces (Ta ble 2 ). T he ne w f or m ulati o ns use d f or eac h treat me nt as defi ne d i n Ta ble 2 will 
be deci de d base d o n t he a vaila bilit y  of ne w f or m ulati o ns. 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 2.
St u d y Desi g n
Se q ue nce
Peri o d 1
Peri o d 2 
Peri o d 3 
Peri o d 4
1 ( n = 3)
A
B
C
D
2 ( n = 3)
B
D
A
C
3 ( n = 3)
C
A
D
B
4 ( n = 3)
D
C
B
A
Treat me nt A = P F -0 7 8 1 7 8 8 3 3 0 0 m g refere nce f or m ulati o n, faste d, D P -0 0 6 0 6 7, 2 3 -D P -0 1 4 4 9  
Treat me nt B = P F -0 7 8 1 7 8 8 3 3 0 0 m g test f or m ulati o n 1, faste d , D P -0 0 6 0 6 7, 2 3 -D P -0 1 5 2 6
Treat me nt C = P F -0 7 8 1 7 8 8 3 3 0 0 m g test f or m ulati o n 2, faste d , D P -0 0 6 9 7 3, 2 3 -D P -0 1 6 8 7
Treat me nt D = P F -0 7 8 1 7 8 8 3 3 0 0 m g test f or m ulati o n 3, faste d , D P -0 0 6 9 7 4, 2 3 -D P -0 1 6 9 6
Healt h y partici pa nts will be scree ne d t o deter mi ne eli gi bilit y  wit hi n 2 8 da ys pri or t o st u d y
treat me nt. Partici pa nts will re p ort t o t he C R U o n Peri o d 1 Da y  -1 ( St u d y  D a y -1) a n d will be 
re q uire d t o sta y at t he C R U u ntil disc har ge . T he partici pa nts will re mai n c o nfi ne d at t he C R U 
u ntil all assess me nts i n all peri o ds are c o m plete.
I n eac h peri o d o n Da y  1, f oll o wi n g a n o ver ni g ht fast of ~ 1 0 h, partici pa nt s will recei ve o ne of 
t he treat me nts as defi ne d i n Ta ble 2. Serial plas ma P K sa m ples will be c ollecte d u p t o 
4 8 h o urs f oll o wi n g t he d ose, at ti mes o utli ne d i n t he S o A. Partici pa nts will als o c o m plete a 
dr u g -pr o d uct acce pta bilit y  q uesti o n naire s h ortly after recei vi n g P F -0 7 8 1 7 8 8 3 i n eac h peri o d . 
At least 4 8 h o urs of was h o ut bet wee n t he d oses of P F-0 7 8 1 7 8 8 3 a d mi nistere d t o a partici pa nt 
i n c o nsec uti ve peri o ds will be i m ple me nte d . D osi n g i n t he s u bse q ue nt peri o d s ca n ta ke place 
i m me diatel y f oll o wi n g t he last P K sa m ple c ollecti o n of a peri o d (S o A , Secti o n 5. 3 ).
A f oll o w -u p ( w hic h m a y  be a p h o ne call) will be ma de t o partici pa nts a p pr o xi matel y 2 8 t o 3 5 
da y s fr o m a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n 
T his st u d y  will e val uate bi oa vaila bilit y of 3 ne w ta blet f or m ulati o ns ( test) of P F - 0 7 8 1 7 8 8 3 
relati ve t o t he c urre nt f or m ulati o n (refere nce) i n healt h y partici pa nts. 
Base d o n t he me dia n half -life of 
 hr, o bser ve d i n C 5 0 9 1 0 0 8 st u d y , w hic h als o use d 3 0 0 m g 
i m me diate release ta blet f or m ulati o n as a S D; t he 
hr was h o ut i nter val is dee me d s ufficie nt 
t o pr o vi de t he c o nce ntrati o n < 5 % of Cma x i n t he s u bse q ue nt peri o d. 
I n st u dy C 5 0 9 1 0 0 1, a d mi nistrati o n of P F -0 7 8 1 7 8 8 3 oral s us pe nsi o n wit h hi g h- fat meal 
decrease d A U C last a n d C ma x b y  
% a n d 
%, res pecti vel y. T h us, t o a v oi d t he p ote ntial effect 
of f o o d o n P F - 0 7 8 1 7 8 8 3 P K, t he partici pa nts will be d ose d i n faste d state i n all peri o ds.
Dr u g pr o d uct acce pta bilit y  q uesti o n naire is a n e x pl orat or y e n d p oi nt t o i nf or m t he f ut ure 
pr o d uct de vel o p me nt.  
Base d i n t he f or m ulati o n, t he test a n d refere nc e f or m ulati o ns are e x pecte d t o ha ve a ver y 
si milar safety pr ofile. I n or der t o li mit t he st u d y -b ur de n t o a partici pa nt, p ost -d ose safety 
la bs/ E C G are n ot pr o p ose d i n eac h peri o d.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 n ot a vaila ble f or P F - 0 7 8 1 7 8 8 3, 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 a n d n o 
e vi de nce f or se vere ma nifestati o ns of de vel o p me ntal t o xicit y  i n n o ncli nical st u dies at 
rele va nt cli nical e x p os ures f or P F-0 7 8 1 7 8 8 3. 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 m a y  be re q uire d as o utli ne d i n A p pe n di x 4 .
4. 3. J ustific ati o n f or D ose
A si n gle oral d ose of 3 0 0 m g will be use d i n t his st u d y . T his d ose has bee n selecte d base d o n
a vaila ble u nit stre n gt h of t he f or m ulati o ns, o bser ve d P K a n d safet y i n healt h y partici pa nts i n 
a n o n g oi n g st u d y C 5 0 9 1 0 0 1. 
 
P F -0 7 8 1 7 8 8 3 was safe a n d well t olerate d i n S A D u p t o 4 0 0 0 m g d ose a n d i n M A D a n d u p t o 
1 5 0 0 m g BI D f or 1 0 da ys. Ma xi m u m t olerate d d ose was n ot ac hie ve d.
 
. T heref ore, a si n gle d ose of 
P F -0 7 8 1 7 8 8 3 at 3 0 0 m g is e x pecte d t o be safe i n healt h y  a d ult partici pa nts t o be e nr olle d i n 
t his st u d y. 
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 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 plete d t he st u d y  if t he y ha ve c o m plete d all peri o ds of 
t he st u d y, i ncl u di n g t he last 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 pa nt p o p ulati o n i ncl u di n g, w here 
per mitte d u n der l ocal re g ulati o ns, a ge, se x, race, a n d et h nicit y . T he f oll o wi n g eli gi bilit y  
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.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 crit eria a p pl y:
A ge a n d Se x :
1.
Male a n d fe male partici pa nts a ge d 1 8 ye ars or ol der ( or t he mi ni m u m a ge of c o nse nt 
i n acc or da nce wit h l ocal re g ulati o ns) at scree ni n g w h o are o vertly healt h y as 
deter mi ne d b y me dical e val uati o n i ncl u di n g me dical hist or y, p h ys ical e xa mi nati o n, 
la b orat or y tests, a n d 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 t o 3 2 k g/ m 2; a n d a t otal b o d y wei g ht >4 5 k g.
3.
Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt 
pla n, la b orat or y  tests, lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n d a y , w hic h i ncl u des 
c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he I C D a n d i n t his 
pr ot oc o l.
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 y c hiatric, ne ur ol o gic al, 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).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V , 
H Bs A g, or H C V A b. He patitis B vacci nati o n is all o we d.
2.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/be ha vi or , la b orat or y a b n or mality , or ot her c o n diti o ns a n d sit uati 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.
P ositi ve test res ult f or S A R S -C o V -2 i nfecti o n at a d missi o n .
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 o mit a nt T he r a p y:
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of m o derate/str o n g C Y P 3 A i n d ucers or ti me-
de pe n de nt i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da 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).
5.
Partici pa nt s w h o ha ve recei ve d a C O VI D -1 9 vacci ne wit hi n 7 da y s bef ore scree ni n g 
or a d missi o n, or w h o are t o be vacci nate d wit h a C O VI D- 1 9 vacci ne at a n y ti me 
d uri n g t he st u d y c o nfi ne me nt peri o d.
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).
Di a g n ostic Assess me nts:
7.
A p ositi ve uri ne dr u g test. 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.
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.
9.
Sta n dar d 1 2- lea d E C G (si n gle) t hat de m o nstrates cli nicall y rele va nt a b n or malities t hat 
ma y
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms,
c o m plete L B B B, si g ns of a n ac ute , or i n deter mi nate-a ge m y 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 y arr h yt h mias or tac h yarr h yt 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 s h o ul d be 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. 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 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 
S cree ni n g, as assesse d b y 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: 

A S T or A L T le vel > 1. 5 × U L N;

T otal bilir u bi n le vel ≥1. 5 × U L N; partici pa nts wit h a hist or y of Gil bert's 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤U L N.

e G F R <6 0 m L /mi n/ 1. 7 3 m 2 base d o n t he C K D -E PI e q u ati o n.
Ot her E xcl usi o n Criteri a :
1 1. 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 2. Use of t o bacc o or nic oti ne c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nts of 
5 ci garettes per da y or 2 c he ws of t o bacc o per da y.
1 3. U n willi n g or u na ble t o c o m pl y  wit h t he criteria i n t he Li fest yle C o nsi derati o ns
S ecti o n 5. 3 of t his pr ot oc ol.
1 4. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers.
1 5. Hist or y  of se nsiti vit y reacti o ns t o P F - 0 7 8 1 7 8 8 3 or a n y  of t he f or m ulati o n c o m p o ne nts 
of P F - 0 7 8 1 7 8 8 3.
1 6. Pre g na nt or breastfee di n g w o me n.
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 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  i nter ve nti o n, if 
a p plica ble.
At ti me p oi nts i n dicate d i n S o A , t he i n vesti gat or or desi g nee will i nf or m t he partici pa nt of 
t he nee d t o use hi g hly effecti ve c o ntrace pti o n c o nsiste ntl y  a n d c orrectl y a n d d oc u me nt t he 
c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart. Partici pa nts nee d t o 
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.
5. 3. 2.
Me als a n d Diet ar y Restricti o ns

Partici pa nts 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 a n d 1 0 h o urs pri or t o t he m or ni n g d ose i n eac h 
peri o d .

Water is per mitte d u ntil 1
h o ur pri or t o st u d y  i nter ve nti o n a d mi nistrati o n i n eac h 
peri o d . Water ma y be c o ns u me d with o ut restricti o n be gi n ni n g 1 h o ur after 
P F - 0 7 8 1 7 8 8 3 d osi n g . N o ncaffei nate d dri n ks (e xce pt re d wi ne, gra pefr uit or 
gra pefr uit -relate d citr us fr uit j uices— see bel o w) ma y be c o ns u me d wit h meals a n d 
t he e ve ni n g s nac k.

L u nc h will be pr o vi de d a p pr o xi matel y  4 h o urs after P F - 0 7 8 1 7 8 8 3 d osi n g .

Di n ner will be pr o vi de d a p pr o xi matel y  9 t o 1 0 h o urs after P F - 0 7 8 1 7 8 8 3 d osi n g.

A n e ve ni n g s nac k m a y be per mitte d .

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi ne, gra pefr uit, or gra pef r uit-relate d 
citr us fr uits (e g, Se ville ora n ges, p o mel os, fr uit j uices) fr o m 7 d a y s pri or t o t he first 
d ose of st u d y i nter ve nti o n u ntil c ollecti o n of t he fi nal P K bl o o d sa m ple.

W hile partici pa nts are c o nfi ne d, t heir t otal dail y  n utriti o nal c o m p ositi o n s h oul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat , a n d 1 5 % pr otei n. T he dail y cal oric i nta ke 
per partici pa nt s h o ul d n ot e xcee d a p pr o xi matel y  3 2 0 0 kcal.
5. 3. 3. C affei ne, Alc o h ol, a n d T o b acc o

Partici pa nts will a bstai n fr o m caffei ne -c o ntai ni n g pr o d ucts wit hi n 2 h o urs o f vitals/ 
E C G meas ure me nts a n d d osi n g . 

Partici pa nts 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 ( or as s pecifie d 
a b o ve f or re d wi ne) t o t he C R U a n d c o nti n ue a bstai ni n g fr o m alc o h ol u ntil c ollecti o n 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
of t he fi nal P K sa m ple. Partici pa nts ma y  u n der g o a n alc o h ol breat h test or bl o o d 
alc o h ol test at t he discreti o n of t he i n vesti gat or.

Partici pa nts will a bstai n fr o m t he use of t o bacc o or nic oti ne -c o ntai ni n g pr o d ucts f or 
2 4 h o urs pri or t o d osi n g a n d d uri n g c o nfi ne me nt i n t he C R U.
5. 3. 4. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea v y lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c ollecti o n f or cli nical 
la b orat or y tests. Wal ki n g at a n or mal pace will be per mitte d;

I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P , P R , a n d E C G 
meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 
4 h o urs after P F -0 7 8 1 7 8 8 3 d osi n g .
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e nr olle d i n t he st u d y. Scree n fail ure data are c ollecte d a n d re mai n as 
s o urce a n d are n ot re p orte d o n t he C R F .
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y  (scree n fail ure) m a y be 
rescree ne d. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal, 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 P F - 0 7 8 1 7 8 8 3.
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 m e
P F - 0 7 8 1 7 8 8 3 
T y pe
Dr u g
Use
E x peri me ntal
I M P or NI M P/ A x M P
I M P
D ose F or m ul ati o n
All test f or m ulati o ns a n d t he refere nce f or m ulati o n are i m me diate 
release ta blets a n d e x pecte d ha ve si milar perf or ma nce . All ta blet 
f or m ulati o ns are of 3 0 0 m g u nit stre n gt h.
U nit D ose Stre n gt h(s)
3 0 0 m g/ ta blet
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 I nter ve nti o n(s)
D os a ge Le vel(s)
3 0 0 m g si n gle d ose per treat me nt, per peri o d. 
R o ute of A d mi nistr ati o n
Oral
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or 
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d i n b ul k . C R U staff will pre pare 
i n di vi d ual d oses f or a d mi nistrati o n. Eac h d ose 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 f or P F-0 7 8 1 7 8 8 3
C urre nt/ F or mer N a me(s) or Ali as(es)
P F -0 7 8 1 7 8 8 3
St u d y Ar m(s)
Ar m Title
A
B
C
D
Ar m Descri pti o n
Partici pa nts will 
recei ve 3 0 0 m g S D 
of refere nce 
f or m ulati o n o n Da y 1 
of t he treat me nt 
peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D 
of test f or m ulati o n 1 
o n Da y 1 of t he 
treat me nt peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D
of test f or m ulati o n 2
o n Da y 1 of t he 
treat me nt peri o d
Partici pa nts will 
recei ve 3 0 0 m g S D of 
test f or m ulati o n 3 o n 
Da y 1 of t he treat me nt 
peri o d
D MI D, L ot
D P - 0 0 6 0 6 7, 2 3-D P -
0 1 4 4 9
D P - 0 0 6 0 6 7, 2 3-D P -
0 1 5 2 6
D P - 0 0 6 9 7 3, 2 3-D P -
0 1 6 8 7
D P - 0 0 6 9 7 4, 2 3-D P -
0 1 6 9 6
P F - 0 7 8 1 7 8 8 3 will be s u p plie d b y  Pfizer as 3 0 0-m g  ta blets.
Ta blets will be s u p plie d t o t he C R U i n b ul k al o n g wit h i n di vi d ual d osi n g c o ntai ners f or u nit 
d osi n g.
6. 1. 1. A d mi nistr ati o n
St u d y  i nter ve nti o ns will be a d mi nistere d orall y a n d acc or di n g t o t he c o n diti o ns descri be d i n
t he S o A secti o n a n d Pr ot oc ol Secti o n 5. 3. 2 .
O n t he d osi n g da y ( Da y 1) i n eac h peri o d, f oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, 
partici pa nts will recei ve o ne of t he P F -0 7 8 1 7 8 8 3 3 0 0 m g f or m ulati o ns as per t he 
ra n d o mizati o n se q ue nce a d mi nistere d orall y i n t he m or ni n g.
In vesti gat or site pers o n nel will a d mi nister st u d y i nter ve nti o n wit h a m bie nt te m perat ure water 
t o a t otal v ol u me of a p pr o xi matel y 2 4 0 m L . Partici pa nt s will s wall o w t he st u d y i nter ve nti o n
w h ole, a n d will n ot ma ni p ulate or c he w t he st u d y i nter ve nti o n pri or t o s wall o wi n g.
I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, all partici pa nts will be re q uire d 
t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P , p ulse rate , a n d E C G 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 4 h o urs after 
d osi n g i n a d diti o n t o ot her s pecificati o ns detaile d i n S ecti o n 5. 3 .
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 w e 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 
1 h o ur 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 ud 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 
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 must 
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 vel y 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o o n as p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y  i nter ve nti o n m ust be 
q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y
i nter ve nti o n. S pecific details re gar di n g t he e xc ursi o n defi niti o n a n d i nf or mati o n t o
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he 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 vesti gat or, i nstit uti o n, hea d of t he me dical i nstit uti o n ( w here a p plica ble), or 
a ut h orize d site staff is res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y,
rec o nciliati o n, a n d rec or d mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal 
dis p ositi o n rec or ds) , s uc h as t he IP A L  or s p o ns or-a p pr o ve d e q ui vale nt . All st u d y  
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 C R U’s l ocal/site pr oce d ures . All destr ucti o n m ust be 
a de q uatel y d oc u me nte d. If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or 
site, t he i n vesti gat or m ust e ns ure t hat t he materials are destr 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 hin 1 b usi ness da y  of 
disc o ver y .
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a d mi nistrati o n or dis pe nsi n g t o t he partici pa nt b y  q ualifie d 
staff. Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mita nt treat me nts, 
a n d acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healt hcare pr o vi der, 
partici pa nt i n acc or da nce wit h t his pr ot oc ol. Local healt h a ut h orit y  re g ulati o ns or i n vesti gat or 
site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
Ta blets 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 ysician, 
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). 
T he ta blets will be pr o vi de d i n u nit d ose c o ntai ners a n d la bele d i n acc or da nce wit h Pfizer 
re g ulati o ns a n d t he cli nical site’s la beli n g re q uire me nts. 
6. 3. Assi g n me nt t o St u d y I n ter ve nti o n
T he i n vesti gat or will assi g n partici pa nt n u m bers t o t he partici pa nt s as t he y are scree ne d f or 
t he st u d y. Pfizer will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or da nce 
wit h t he ra n d o mizati o n n u m bers, t he partici pa nt will recei ve t he st u d y treat me nt re gi me n 
assi g ne d t o t he c orres p o n di n g ra n d o mizati o n n u m ber.
6. 4. Bli n di n g
T his is a n o pe n la bel st u d y. 
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n t he i n di vi d ual d ose f or a partici pa nt is pre pare d fr o m a b ul k s u p pl y, t he pre parati o n of 
t he d ose will be c o nfir me d b y a sec o n d q ualifie d me m ber of t he st u d y site staff.
W he n partici pa nts are d ose d at t he site, t he y  will recei ve st u d y i nter ve nti o n directl y fr o m t he 
i n vesti gat or or desi g nee, u n der me dical s u per visi o n. T he date an d ti me of eac h d ose 
a d mi nistere d i n t he cli nic will be rec or de d i n t he s o urce d oc u me nts a n d rec or de d i n t he C R F. 
T he d ose of st u d y i nter ve nti o n a n d st u d y partici pa nt i de ntificati o n will be c o nfir me d at t he 
ti me of d osi n g by a me m ber of t he st u d y site staf f ot her t ha n t he pers o n a d mi nisteri n g t he 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
st u d y i nter ve nti o n. St u d y site pers o n nel will e xa mi ne eac h partici pa nt’s m o ut h t o e ns ure t hat 
t he st u d y i nter ve nti o n was i n geste d.
6. 6. D ose M o dific ati o n
N o d ose m o dificati o n is a ntici pate d.
6. 7. C o nti n ue d Access t o St u d y Inter 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.
It is e x pecte d t hat partici pa nts will be treate d as re q uire d wit h sta n dar d-of -care treat me nts, as 
a d vise d b y t heir us ual care p h ysicia 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 P F - 0 7 8 1 7 8 8 3 greater t ha n
m g wit hi n a 2 4- h o ur ti me peri o d 
± 2 h o urs 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 ort a ble t o Pfizer Safet y o nl y w he n ass oci ate d wit h a n S A E.
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 1 da y fr o m t he date of t he last d ose of 
st u d y i nter ve nti o n if re q ueste d b y t he st u d y me dical m o nit or ( deter mi ne d o n a 
case-b y -case basis).
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 wit h t he e xce pti o n of m o derate/str o n g C Y P 3 A i n d ucers or ti me- de pe n de nt 
i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o t he first d ose of st u d y 
i nter ve nti o n. Li mite d use of n o n prescri pti o n me dicati o ns t hat are n ot belie ve d t o affect 
partici pa nt safet y  or t he o verall res ults of t he st u d y ma y be per mitte d o n a case-b y -case basis 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
f oll o wi n g a p pr o val by t he s p o ns or . Aceta mi n o p he n/ paraceta m ol ma y  be use d at d oses of 
≤1 g/ da y .
H or m o nal c o ntrace pti ves t hat meet t he re q uire me nts of t his st u d y  are all o we d t o be use d i n 
partici pa nts w h o are W O C B P (see A p pe n di x 4 ).
All c o nc o mita nt treat me nts ta ke n d uri n g t he st u d y  m ust be rec or de d wit h i n dicati o n, dail y 
d ose, a n d start a n d st o p dates of a d mi nistrati o n. All partici pa nts will be q uesti o ne d a b o ut 
c o nc o mita nt treat me nt at eac h cli nic visit.
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.
6. 9. 1. Resc ue Me dici ne 
T here is n o resc ue t hera p y t o re verse t he A Es o bser ve d wit h P F- 0 7 8 1 7 8 8 3. Sta n dar d me dical 
s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es.
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 n ti 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 uati o n i n i n vesti gat or’s vie w;

Pre g na nc y .
If st u d y i nter ve ntio 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 C l) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter- me diate d effect relate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
A KI m a y  be d ue t o o ne or m ore ty pes of i nj ur y, i ncl u di n g DI KI. Differe ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y  c o ns ultati o n.
F oll o w -u p Assess me nts
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 xami nati o n, la b orat or y  tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs a n d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates of e G F R, e Cr Cl a n d Screat -base d e G F R a n d c o m bi ne d 
Screat -S c y s-base d e G F R s h o ul d als o be deri ve d usi n g t he a p pr o priate e q ua ti 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
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is (i) ne w-o nset or w orse ni n g al b u mi n uria or pr otei n uria are 
detecte d .
All c o nfir me d cases of cli nicall y  rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d 
p ote ntial cases of DI KI if n o ot her reas o n f or t he ki d ne y f u ncti o n a b n or malities has bee n 
f o u n d.
7. 1. 2. E C G C h a n ges
A partici pa nt w h o meets eit her b ullete d criteri o n base d o n t he a vera ge of tri plicate E C G 
rea di n gs will be wit h dra w n fr o m t he st u dy i nter ve nti o n. 

Q Tc F > 5 0 0 ms.

C ha n ge fr o m baseli ne: Q Tc F > 6 0 ms a n d Q Tc F > 4 5 0 ms.
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q Tc F after e nr oll me nt), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d. T his re vie w of t he E C G pri nte d at t he ti me of c ollecti o n m ust be d oc u me nte d. A n y 
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h d r 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 f oll o w -u p;

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;

I n vesti gator’s decisi o n;

Pre g na nc y .
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d . See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y. Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
8. 1. A d mi nistr ati ve a n d B aseli ne Pr oce d ures
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures. 
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d .
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Partici pa nt s will be scree ne d wit hi n 2 8 da y s pri or t o a dmi 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 req 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 t his st u d y. I n 
a d diti o n, ot her cli nical assess me nts or s peci me n c ollecti o ns, e g, retai ne d researc h sa m ples, 
ma y  n ot nee d t o be re peat e 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 n y c orrecti ve a n d pre ve nti ve 
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
If a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g n assess me nts 
(p ulse rate a n d B P) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T 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 
2 7 0 m L . T he act ual c ollecti o n ti mes of bl o o d sa m pli n g ma y  c ha n ge. A d diti o nal bl o o d 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ny peri o d of 5 6 c o nsec uti v e 
da y s.
T o pre pare f or st u d y partici pati o n, partici pa nt s will be i nstr ucte d o n t he i nf or mati o n i n t he 
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
8. 1. 1. 1. Me dic al Hist or y
A detaile d me dical hist or y will be re vie we d a n d rec or de d at scree ni n g a n d u p date d o n 
a d missi o n. T his will i ncl u de detaile d me dical hist or y  as well as a hist or y of pri or ille gal dr u g, 
alc o h ol, a n d t o bacc o use wit hi n 6 0 da y s pri or t o e nr oll me nt. If t he partici pa nts are disc har ge d 
bet wee n t he peri o ds , me dical hist or y ma y be u p date d.
8. 1. 1. 2. De m o gr a p hics
Partici pa nts’ race, et h nicit y , a ge, ge n der, hei g ht, a n d wei g ht will be rec or de d at scree ni n g. 
8. 2. Effic ac y Assess me nts
Efficac y  para meters are n ot e val uate d i n t his st u d y . 
8. 3. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d safet y
meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess a n y percei ve d safet y 
iss ues.
8. 3. 1. Vit al Si g ns
8. 3. 1. 1. Bl o o d Press ure a n d P ulse R ate
S u p i 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 rate s h o ul d be o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n.
A d diti o nal c ollecti o n ti mes, or c ha n ges t o c ollecti o n ti mes, of B P a n d p ulse rate will be 
per mitte d, as necessar y , t o e ns ure a p pr o priate c ollecti o n of safet y data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 3. 2. P h ysic al E x a mi n ati o ns
A c o m plete p h ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, hea d, ears, e y es, 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 ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of ge neral a p peara nce, 
t he res pirat or y a n d car di o vasc ular sys te ms, a n d partici pa nt-re p orte d sy m pt o ms.
P h y sical e xa mi nati o ns ma y be c o n d ucte d b y a p hysicia n, trai ne d p h ys icia n’s assista nt, or 
n urse practiti o ner as acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets so 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 dere d s o urce rec or d 
an 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. 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 m s; 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 u n der g o c o nti n u o us E C G m o nit ori n g. A car di ol o gist s h o ul d be c o ns ulte d if Q TcF
val ues d o n ot ret ur n t o less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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, r e 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 b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A . 
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y si g nifica nt c ha n ges occ urri n g d uri n g t he st u d y  i n t he A E secti o n of t he C R F. 
Cli nicall y  si g nifica nt a b n or mal la b orat or y test fi n di n gs are t h ose t hat are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i n vesti gat or t o be m ore se vere t ha n e xpecte 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 ide 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 ust be ne gati ve f or partici pa nt s t o recei ve st u d y 
i nter ve nti o n. 
8. 3. 5. C O VI D - 1 9 Specific A ssess me nts 
C O VI D -1 9 relate d pr oce d ures as per t he S o A a n d l ocal re g ulati o ns. A d diti o nal testi n g ma y  
be re q uire d b y t he PI .
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 4
8. 3. 6. Pre g n a nc y Testi n g 
A uri ne or ser u m pre g na nc y test is re q uire d at scree ni n g. F oll o wi n g scree ni n g, p re g na nc y 
tests ma y be uri ne or ser u m tests, a n d m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L. 
Pre g na nc y  tests will be perf or me d i n W O C B P at t he ti mes liste d i n t he S o A . F oll o wi n g a 
ne gati ve pre g na nc y  test res ult at scree ni n g, a p pr o priate c o ntrace pti o n m ust be c o m me nce d 
a n d a sec o n d ne gati ve pre g na nc y  test res ult will be re q uire d at t he baseli ne visit pri or t o 
starti n g t he st u d y i nter ve nti o n. Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c ycle 
is misse d d uri n g t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise 
s us pecte d) a n d at t he e n d of t he st u d y. Pre g na nc y tests ma y  als o be re peate d if re q ueste d by 
I RBs/ E C s or if re q uire d b y l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d as ne gati ve 
(e g, a n a m bi g u o us res ult), a ser u m pre g na nc y test is re q uire d. I n s uc h cases, t he partici pa nt 
m ust be e xcl u de d if t he ser u m p re 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, t est 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 h e o utc o me a n d t o assess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o 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 uesti o ne d a b o ut t he occ urre nce of A E s i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y  Pfizer Safety t o o btai n s pecific f oll o w -u p 
i nf or mati o n i n a n e x pe dite d fas hi o n.
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g AE s a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore u n der g oi n g a n y st u d y- relate d pr oce d ure a n d/ or recei vi n g st u d y 
i nter ve nti o n), t hr o u g h a n d i ncl u di n g a mi ni m u m of 2 8 cale n dar da ys after t he last 
a dmi 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.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
W he n a cli nicall y  i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
F or partici pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c onse 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 ncl u de d st u d y part ici pati o n, a n d t he y
c o nsi der t he e ve nt t o be reas o na bl y relate d t o t he st u d y  i nter ve nti o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m .
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n 
Secti o n 8. 4. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m i m me diatel y u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it s bei n g a vaila ble.
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 4 . 1, will be rec or de d 
o n t he A E secti o n of t he C R F.
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y re p orte d 
A E s a n d S A Es re p orte d b y t he partici pa nt.
As part of o n g oi n g safet y re vie ws c o n d ucte d b y t he s p o ns or, a n y n o nseri o us A E t hat is 
deter mi ne d b y t he s p o ns or t o be seri o us will be re p orte d b y t he s p o ns or as a n S A E. T o assist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
Re p orti n g of A E s 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 .
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 .
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 -U p 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 u ate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w-u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi nati o n of 
p ossi ble ca usalit y . A ny i nf or mati o n rel e 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 safety 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 S A E. Pers o ns at ris k f or e n vir o n me ntal 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
e x p os ure i n cl 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.
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 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.
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 2 8 da y s 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 nfor 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 p re 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 uld be assesse d b y gr oss vis ual i ns pecti o n ( u nless pre -pr oce d ure test 
fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o maly a n d t he fi n di n gs are re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. If t he o utc o me of t he pre g na nc y meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y , s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
de mise, ne o natal deat h, or c o n ge nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b o ut pre g na nc y o utc o mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n s h o ul d be re p orte d 
as a n S A E ;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut 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 di ti o nal i nf or mati o n re gar di n g t he E D P ma y be re q ueste d b y t he s p o ns or. F urt her 
f oll 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 to pr o vi de t o his 
part ner.
8. 4. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n E D B occ urs if:

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male n o n partici pa nt is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g 
bee n e x p ose d t o st u d y  i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of 
e n vir o n me ntal E D B is a fe male fa mily me m ber or healt hcare pr o vi der w h o re p orts 
t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y 
i n gesti o n. 
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 orte d 
usi n g t he C T S A E Re p ort F or m . W he n E D B occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, 
t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, s o t he 
i nf or mati o n is n ot rec or de d o n a C R F. H o we ver, a c o p y  of t he c o m plete d 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 created w he n a Pfizer dr u g s pecificall y 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 or m re gar dless of w het her 
t here is a n ass ociate d S A E. Si nce t he i nf or mati o n ab o ut t he occ u pati o nal e x p os ure d oes n ot 
pertai n t o a partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; 
h o we ver, a c o p y of t he c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file .
8. 4. 6. C ar di o v asc ul ar a n d De at h E ve nts
N ot a p plica ble.
8. 4. 7. Dise ase -Rel ate d E ve nts a n d/ or Dise ase -Rel ate d O utc o mes N ot Q u alif yi n g as A E s 
or S A Es
N ot a p plica ble.
8. 4. 8. A d verse E ve nts of S peci al I nterest
A E SI s are e xa mi ne d as part of r o uti ne safet y data re vie w pr oce d ures t hr o u g h o ut t he cli nical 
trial a n d as part of si g nal detecti o n pr ocesses. S h o ul d a n a g gre gate a nal y sis i n dicate t hat 
t hese pres pecifie d e ve nts occ ur m ore fre q ue ntly t ha n e x pecte d, e g, base d o n e pi de mi ol o gical 
data, literat ure, or ot her data, t he n t his will be s u b mitte d a n d re p orte d i n acc or da nce wit h 
Pfizer’s safet y re p orti n g re q uire me nts. A g gre gate a nal ys es of safet y data will be perf or me d 
o n a re g ular basis per i nter nal S O P . 
All A E SI s m ust be re p orte d as a n A E or S A E f oll o wi n g t he pr oce d ures descri be d i n 
Secti o n 8. 4. 1 t hr o u g h 8. 4. 4 . A n A E SI is t o be rec or de d as a n A E or S A E o n t he C R F. I n 
a d diti o n, a n A E SI t hat is als o a n S A E m ust be re p orte d usi n g t he C T S A E Re p ort F or m .
8. 4. 8. 1. L ac k of Effic ac y
T his secti o n is n ot a p plica ble beca use efficac y  is n ot e x pecte d i n t he st u d y p o p ulati o n.
8. 4. 9. Me dic al De vice Deficie ncies
N ot a p plica ble.
8. 4. 1 0. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y 
i nter ve nti o n b y  t he wr o n g partici pa nt , or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 .
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 
Bl o o d sa m ples of a p pr o xi matel y  4 m L, t o pr o vi de a p pr o xi matel y 1. 5 m L of plas ma, will be
c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 as s pecifie d i n t he S o A .
I nstr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he
la b orat or y ma n ual or b y t he s p o ns or. T he act ual date a n d ti me ( 2 4-h o ur cl oc k ti me) of eac h
sa m ple will be rec or de d.
T he act ual ti mes ma y  c ha n ge, b ut t he n u m ber of sa m ples will re mai n t he sa me. All eff orts
will be ma de t o o btai n t he sa m ple s at t he e xact n o mi nal ti me relati ve t o d osi n g. C ollecti o n of
sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d wit hi n 1 0 % 
of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n utes of a 6 0 - mi n ute sa m ple) will n ot 
be ca pt ur e d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n t he 
s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 1 0 h o urs after d ose
a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y  fr o m t he n o mi nal ti me relati ve t o d osi n g will
n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n
t he s o urce d oc u me nt a n d t he C R F.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Sa m ples will be use d t o e val uate t he P K of P F - 0 7 8 1 7 8 8 3. Sa m ples c ollecte d f or a nalys es of
P F -0 7 8 1 7 8 8 3 plas ma c o nce ntrati o n ma y  als o be use d t o e val uate safety or efficac y  as pects
relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y, f or meta b olite i de ntificati o n a n d/ or
e val uati o n of t he bi oa nal ytical met h o d, or f or ot her i nter nal e x pl orat or y  p ur p oses. T he
e x pl orat or y res ult s ma y n ot be re p orte d i n t he C S R.
Ge netic a nal ys es will n ot be perf or me d o n t hese P K plas ma sa m ples u nless c o nse nt f or t his
was i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y  will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 will be
a nal yz e d usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h a p plica ble S O Ps. P ote ntial
meta b olites ma y  be a nalyze d wit h eit her vali date d or e x pl orat or y met h o ds.
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y de viati o ns fr o m t he P K sa m ple
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g
c o n diti o ns), i ncl u di n g a n y acti o ns t a ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or.
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple
i nte grity has bee n c o m pr o mise d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol de viati o n. T he IR B/ E C will be
i nf or me d of a ny s afet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or
a me n d me nt of t he I C D.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
S pecifie d g e netic a nal ys es are n ot e val uate d i n t his st u d y .
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
Retai ne d researc h sa m ples f or ge netics will n ot be c ollecte d i n t his st u d y.
8. 7. Bi o m ar kers
B i 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.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 1 0. Dr u g Pr o d uct Acce pt a bilit y Q uesti o n n aire
T he acce pta bilit y  attri b utes of P F-0 7 8 1 7 8 8 3 will be e val uate d b y  t he partici pa nt usi n g a Dr u g 
Pr o d uct Acce pta bilit y  Q uesti o n naire (A p pe n di x 8 ). In eac h peri o d , eac h partici pa nt will 
c o m plete t he Dr u g Pr o d uct Acce pta bilit y  Q uesti o n naire i m me diately f oll o wi n g d osi n g. All 
eff orts will be ma de t o i nitiate t he q uesti o n naire i m me diatel y  f oll o wi n g d osi n g; h o we ver, it 
will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti m e of assess me nt is n ote d 
o n t he s o urce d oc u me nt a n d t he C R F.
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 heses
T here are n o statistical h y p ot heses f or t his st u d y .
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d 
“E nr olle d ” mea ns a partici pa nt ’s, or t heir le gall y a ut h orize d 
re prese ntati ve’s, a gree me nt t o partici pate i n a cli nical st u d y 
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
ra n d o mizati o n t o st u d y i nter ve nti o n. 
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 i n at least o ne 
treat me nt peri o d. Partici pa nts will be a nal yz e d acc or di n g t o t he 
pr o d uct t he y act uall y recei ve d.
P K C o nce ntrati o n 
a nal ys is set
T he P K c o nce ntrati o n p o p ulati o n is defi ne d as all partici pa nt s 
ra n d o mize d a n d treate d w h o ha ve at l east 1 c o nce ntrati o n val ue 
i n at least 1 treat me nt peri o d.
P K Para meter a nal ys is 
set
T he P K para meter a nal ys is p o p ulati o n is defi ne d as all 
partici pa n ts ra n d o mize d a n d treate d w h o ha ve at least 1 of t he 
P K para meters of i nterest i n at least 1 treat me nt pe ri o d.
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y a nalys es are p erf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data.
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t he pri mar y a n d sec o n dar y 
e n d p oi nts.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 1. Ge ner al C o nsi der ati o ns
All data will be prese nte d b y  treat me nt gr o u ps a n d b y t otal. Descri pti ve statistics will be 
pr o vi de d. T he f oll o wi n g listi n g of i n di vi d ual partici pa nts data m a y als o be pr o d uce d: 
Dis p os iti o n E ve nts, P ote ntiall y Im p orta nt Pr ot oc ol De viati o ns, S u bject E val uati o n Gr o u ps, 
De m o gra p hic I nf or mati o n, C o nc o mita nt Me dicati o ns, C o m plia nce wit h St u d y I nter ve nti o n.
9. 3. 2. Pri m ar y E n d p oi nt(s) A n al ysis
9. 3. 2. 1. Defi niti o n of E n d p oi nt(s)
T he pri mar y  e n d p oi nts are t he plas ma P K e n d p oi nts C ma x a n d A U C i nf (if data per mits)
ot her wise A U C last.
T he a nal ys es f or t he pri mar y e n d p oi nts are descri be d i n Secti o n 9. 3. 2. 2.
9. 3. 2. 2. M ai n A n al ytic al A p pr o ac h
Plas ma P K para meters of P F - 0 7 8 1 7 8 8 3 will be deri ve d (as data per mit) fr o m t he 
c o nce ntrati o n-ti me data usi n g sta n dar d n o nc o m part me ntal met h o ds as o utli ne d i n Ta ble 3.
Act ual P K sa m pli n g ti mes will be use d i n t he deri vati o n of P K para meters. I n t he case t hat 
act ual P K sa m pli n g ti mes are n ot a vaila ble, n o mi nal P K sa m pli n g ti me will be use d i n t he 
deri vati o n of P K para meters. 
T a ble 3.
Pl as m a P F - 0 7 8 1 7 8 8 3 P K P ar a meters Defi niti o ns
P a r a m eter
Defi niti o n
M e t h o d of Deter mi n ati o n
A U C i nf*
Area u n der t he c o nce ntrati o n -ti me c ur ve fr o m 
ti me 0 e xtra p olate d t o i nfi nit y
A U C last + ( C last*/ k el),
w here C last* is t he pre dicte d plas ma 
c o nce ntrati o n at t he last q ua ntifia ble 
ti me p oi nt fr o m t he l o g-li near 
re gressi o n a nal ysis
A U C lasta
Area u n der t he plas ma c o nce ntrati o n -ti me pr ofile 
fr o m ti me 0 t o t he ti me of t he last q ua ntifia ble 
c o nce ntrati o n ( C last).
Li near/ L o g tra pez oi dal met h o d.
C ma x
Ma xi m u m o bser ve d c o nce ntrati o n
O bser ve d directl y fr o m data
C 1 2
C o nce ntrati o n o bser ve d at 1 2 h o urs
O bser ve d directl y fr o m data
T ma x
Ti m e f or C ma x
O bser ve d directl y fr o m data as ti me of 
first occ urre nce
t½ *
T er m i nal half-life
L o g e( 2)/ kel, w here kel is t he ter mi nal 
p hase rate c o nsta nt calc ulate d b y a 
li near re gressi o n of t he l o gli near 
c o nce ntrati o n-ti me c ur ve. O nl y t h ose 
data p oi nts j u d ge d t o descri be t he 
ter mi nal l o gli near decli ne will be use d 
i n t he re gressi o n.
C L/ F *
A p pare nt cleara nce
D ose/ A U C i nf
V z/ F *
A p pare nt v ol u me of distri b uti o n
D ose/( A U C i nf • k el)
* If data per mit.
a.
4 8 h P K sa m ple i n Peri o ds 1 t o 3 will be c o nsi dere d 0 h P K sa m ple f or t he s u bse q ue nt peri o d.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 2. 2. 1. St atistic al Met h o ds f or P K d at a
F or t he pri mar y  o bjecti ve, n at ural l o g tra nsf or me d A U C i nf (if data per mit), ot her wise A U C last,
a n d C ma x f or P F - 0 7 81 7 8 8 3 will be a nal yz e d usi n g a mi xe d effect m o del wit h se q ue nce, 
peri o d a n d treat me nt as fi xe d effects a n d p artici pa nt wit hi n se q ue nce as a ra n d o m effect i n 
Peri o ds 1 t o 4 . Esti mates of t he a dj uste d mea n differe nces (t est-refere nce) a n d c orres p o n di n g 
9 0 % c o nfi de nce i nter vals will be o btai ne d fr o m t he m o del. T he a dj uste d mea n differe nces 
a n d 9 0 % c o nfi de nce i nter vals f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates 
of t he rati o of a dj uste d ge o metric mea ns ( test/refere nce) a n d 9 0 % c o nfi de nce i nter vals f or t he 
rati os. Treat me nt A will be t he Refere nce treat me nt w hile Treat me nt s B, C, a n d D will be t he 
Test treat me nt s.
P K para meters, i ncl u di n g plas ma A U C i nf (if data per mit), A U Clast, Cma x , a n d T ma x , t½ (if data 
per mit) of P F - 0 7 8 1 7 8 8 3 will be s u m marize d descri pti vel y  b y treat me nt. F or A U Ci nf (if data 
per mit) , A U Clast, a n d C ma x , a listi n g of t he i n divi d ual partici pa nt rati os ( test/refere nce) will be 
pr o vi de d. B o x a n d w his ker pl ots f or A U C i nf (if data per mit), A U Clast, a n d C ma x , will be 
pl otte d b y  treat me nt.
T he plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 will be liste d a n d descri pti vel y s u m marize d b y 
n o mi nal P K sa m pli n g ti me a n d treat me nt. I n di vi d ual partici pa nt, as well as mea n a n d me dia n 
pr ofiles of t he plas ma c o nce ntrati o n ti me data will be pl otte d b y  treat me nt usi n g act ual (f or 
i n di vi d ual) a n d n o mi nal (f or mea n a n d me dia n) ti mes res pecti vely. Mea n a n d me dia n pr ofiles 
will be prese nte d o n b ot h li near a n d se mi -l o g scales. 
A d diti o nal s pecificati o ns a b o ut t he ta bles, listi n gs, a n d fi g ures will be o utli ne d i n t he S A P.
9. 3. 3. Sec o n d ar y E n d p oi nt(s) A n al ysis
T he a nal ys es f or safet y e n d p oi nts are descri be d i n Secti o n 9. 3. 5.
9. 3. 4. Terti ar y/ E x pl or at or y E n d p oi nt(s) A n al ysis
T he a nal ys es of t he plas ma P K para meters are descri be d a b o ve i n Secti o n 9. 3. 2. 2 .
T he ite m a n d d o mai n sc ores fr o m t he dr u g -pr o d uct acce pta bilit y  q uesti o n naire (A p pe n di x 8 ) 
f or eac h test f or mati o n a n d t he refere nce f or m ulati o n will be liste d a n d descri pti vel y
s u m marize d a n d a p pr o priate pl ots ma y be ge nerate d.
T he s u m mar y  a n d a nalys is of t he dr u g pr o d uct acce pta bi lit y q uesti o n naire res p o nses m a y  or 
ma y  n ot be re p orte d i n t he C S R.
9. 3. 5. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he s afet y p o p ulati o n.
A E s, E C Gs, vital si g ns , a n d safety 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 safet y of partici pa nt s. A ny cl i nical la b orat or y, 
E C G, a n d vital si g n a b n or malities of p ote ntial cli nical c o ncer n will be descri be d. Safet y dat a 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ns i dere d s o urce data a n d will 
n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. H o we ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d d uri n g t he acti ve 
c ollecti o n peri o d will be ca pt ure d as A E s, if t h ose fi n din 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.
9. 3. 5. 1. Electr oc ar di o gr a m A n al yses
C ha n ges fr o m baseli ne f or t he E C G para meters H R , Q TcF , P R i nter val, a n d Q R S i nter val 
will be s u m marize d b y  treat me nt a n d ti me. 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 nt s 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 b y treat me nt: 
S afet y Q Tc F Assess me nt
De gree of Pr ol o n g ati o n
Mil d
( ms)
M o der ate
(ms)
Se vere ( m s)
A bs ol ute val ue
> 4 5 0 -4 8 0
> 4 8 0 -5 0 0
> 5 0 0
I ncrease fr o m b aseli ne
3 0 -6 0
> 6 0
9. 3. 6. Ot her A n al yses 
P har mac o ge n o mic or bi o mar ker data fr o m Retai ne d Researc h Sa m ples ma y  be c ollecte d 
d uri n g or after t he trial a n d retai ne d f or f ut ure a nal yses; t he res ults of s uc h a nal ys es are n ot 
pla n ne d t o be i ncl u de d i n t he C S R.
9. 4. I nteri m A n al yses
N o i nteri m a nal ys is will be c o n d ucte d f or t his st u d y. As t his is a n o pe n -la bel st u d y, t he
s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g t he c o urse of t he st u d y f or t he 
p ur p ose of safet y assess me nt, facilitati n g P K/ P D m o deli n g, a n d/ or s u p p orti n g cli nical 
de vel o p me nt. 
9. 5. S a m ple Size Deter mi n ati o n
A sa m ple size of a p pr o xi matel y 1 2 partici pa nts wit h at least 8 c o m pleters was c h ose n t o
pr o vi de a de q uate precisi o n t o c o m pare t he relati ve bi oa vaila bilit y  of test f or m ulati o ns of P F -
0 7 8 1 7 8 8 3 relati ve t o t he refere nce f or m ulati on i n Peri o ds 1 t hr o u g h 4 , base d o n esti mates of 
t he wit hi n- partici pa nt sta n dar d de viati o ns of 
f or l o ge A U C i nf,
f or l o ge A U C last
a n d
f or l o ge C ma x . T he e x pecte d wi dt hs of t he 9 0 % CIs wit h 8 0 % c o vera ge pr o ba bilit y  
f or t he c o m paris o n of t he test f or m ulati o ns of P F -0 7 8 1 7 8 8 3 relati ve t o refere nce f or m ulati o n
are s h o w n i n Ta ble 4 for a ra n ge of p ossi ble effects.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 4.
E x pecte d Wi dt hs of t he 9 0 % CIs ( wit h 8 0 % C o ver a ge Pr o b a bilit y) f or 
Differe nt P ossi ble Esti m ate d Effects f or A U C i nf, A U C l ast, a n d C m a x
A s ufficie nt n u m ber of partici pa nts will be scree ne d t o ac hie ve a p pr o xi matel y 1 2 partici pa nts 
ra n d o mize d t o treat me nt se q ue nce ( 3 per eac h se q ue nce) s uc h t hat t here will be
a p pr o xi matel y 8 e val ua ble partici pa nts c o m pleti n g t he st u d y f or a n esti mate d t otal of 2
e val ua ble partici pa nts per se q ue nce . Partici pa nts disc o nti n ui n g f or n o n- safet y reas o ns ma y be 
re place d at t he s p o ns or’s discreti o n.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 S t u d y O versi g ht C o nsi der ati o ns
1 0. 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes , i ncl u di n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes ;

A p plica ble I C H G C P g ui deli nes ;

A p plica ble la ws a n d re g ulati o ns , i ncl u di n g a p plica ble pri vac y la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, S R S D(s) , a n d ot her rele va nt d oc u ments 
(e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y t he s p o ns or, s u b mitte d t o a n IR B/ E C 
b y  t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y  t he I R B/ E C bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire 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 ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 n y 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 nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts will be 
re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, 
l ocal re g ulati o ns, I C H g ui deli nes, pri vac y  a n d data pr otecti o n re q 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 r is ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt ’s 
pers o nal data. 
T he partici pa nt m ust be i nf or me d t hat t heir pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m r e g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt is f ull y i nf or me d a b o ut t heir
ri g ht t o access a n d c orrect t heir pers o nal data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of 
t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C D.
Partici pa n ts 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 1 0 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 ur es 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 orize 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 
dete r 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 sin 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 ide 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 c li 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 b y  tec h nical a n d or ga nizati o nal sec urity 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, o r 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 0. 1. 4. C o m mittees Str uct ure
1 0. 1. 4. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use an E- D M C.
1 0. 1. 5. Disse mi n ati o n of 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 ng 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 utside of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 hi c h t he st u d y was c o n d ucte d.
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer- s p o ns ore d i nter ve nti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a 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 an 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 pse s 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 on y mize 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 bl e pri vac y la ws a n d re g ulati o ns. C S Rs will ha ve pers o nally i de ntifia ble 
i nf or mati o n a n o n y m ize d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal yses. Researc h tea ms m ust i ncl u de a bi ostat isticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 1. 6. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or d e d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
G u i 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 ds, res p o nsi bilities , a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n 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 n si 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 otifi cati 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 irrev oca bl y delete d fr o m all s yste ms.
T he i n vesti gat or(s) will n otif y  t he s p o ns or or its a ge nts i m me diatel y of a n y re g ulat or y 
i ns pecti o n n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perate 
wit h t he s p o ns or or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he 
i n vesti gat or site a n d i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
bet wee n t he st u d y data a n d t he partici pa nt ’s me dical rec or ds. T he i n vesti gat or will pr o m ptl y 
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt. Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he i n vesti gat or will pr o vi de t he s p o ns or or its 
age 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 1. 7. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nts are file d at the 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.
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 ot ecte 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. 8. Use of Me dic al Rec or ds
T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d by 
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/fa x n u m ber, e mail a d dress).

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). 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 3
T here ma y  be u n pla n ne d sit uati o ns w here t he s p o ns or ma y re q uest me dical rec or ds (e g, 
s hari n g me dical rec or ds s o t hat t he s p o ns or ca n pr o vi de st u d y-relate d a d vice t o t he 
i n vesti gat or). T he me dical rec or ds s h o ul d be s u b mitte d acc or di n g t o t he pr oce d ure descri be d 
a b o ve.
1 0. 1. 9. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or , i nclu 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 dy- 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 if re q ueste d t o d o s o b y t he res p o nsi ble I R B/ E C or if s uc h ter mi nati o n is re q uire d 
t o pr otect t he healt h of st u d y partici pa nts.
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or ’s pr oce d ures, or t he I CH G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t h e c o ntract a n d t his pr ot oc ol , t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 1 0. 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 st u d y c o ntact list l ocate d i n t he C T M S. 
T o facilitate access t o t heir i n vesti gat or a n d t he s p o ns or’s M QI f or st u d y-relate d me dical 
q uesti o ns or pr o ble ms fr o m n o n-st u d y healt hcare pr ofessi o nals, 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 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ys 
bet wee n t he partici pa nt a n d t heir i n vesti gat or a n d site staff, a n d bet wee n t he i n vesti gat or a n d 
s p o ns or st u d y tea m. T he E C C is o nl y t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n 
t he researc h st u dy, as a mea ns of reac hi n g t he i n vesti gat or or site staff relate d t o t he care of a 
partici pa nt. 
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 a ble 5.
Pr ot oc ol -Re q uir e 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)
M C V
M C H
M C H C
Urea
Creati ni ne
C ystati n C a
e G F R, e Cr Cl b
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T
T otal bilir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u m i n
T otal pr otei n
L ocal di pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y a n d 
cult ure c
C O VI D -1 9 testi n g
Uri ne dr u g scree ni n g e
Pre g na nc y test ( β- h C G) f
At scree ni n g:

F S H d

H Bs A g

H Bs A b g

H Bc A b

H C V A b

HI V
a.
C ystati n C ( Sc ys):  Scree ni n g or Baseli ne Sc ys is rec o m me n de d t o hel p differe ntiate p ost -baseli ne DI KI
fr o m DI CI. P ost- baseli ne, Sc ys is meas ure d if a n d o nl y if ser u m creati ni ne i ncrease p ost -baseli ne is 
o bser ve d (see Secti o n 7. 1. 1 ).
b.
Scree ni n g a n d Baseli ne e G F R or e Cr Cl is 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 di aze 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 re g ulati o n 
or I R B/ E C. See S o A f or c ollecti o n ti mes.
g.
Ca n be d o ne eit her a ut o maticall y or o nl y if H Bc A b or H Bs A g is p ositi ve, as per l ocal practices.
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 safet y 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 
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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 -U p, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or 
n ot c o nsi dere d relate d t o t he st u d y  i nter ve nti o n.

N ote : A n A E ca n t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or 
uri nal y sis) or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y  
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or. A n y 
a b n ormal 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 o s pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or 
o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h y sicia n’s 
office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A 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 w as 
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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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 ub missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0. 1. 9 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her c li nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis 
( n ot t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E or S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: A t y pe of A E t hat is us uall y  tra nsie nt a n d ma y re q uire o nl y mi ni mal 
treat me nt or t hera pe utic i nter ve nti o n. T he e ve nt d oes n ot ge nerall y i nterfere wit h 
us ual A D L .

M o derate: A t y pe of A E t hat is us uall y  alle viate d wit h a d diti o nal s pecific 
t hera pe utic i nter ve nti o n. T he e ve nt i nterferes wit h us ual A D L , ca usi n g 
disc o mf ort , b ut p oses n o si g nifica nt or per ma ne nt ris k of har m t o t he researc h 
partici pa nt.

Se vere: A t y pe of A E t hat i nterr u pts us ual A D L , or si g nifica ntl y affects cli nical 
stat us, or ma y re q uire i nte nsi ve t hera pe utic i nter ve nti o n.
A n e ve nt is defi ne d as “seri o us” w he n it meets at least 1 of t he pre defi ne d o utc o mes as 
descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
Assess me nt of C a us alit y

T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n 
a n d eac h occ urre nce of eac h A E or S A E. T he i n vesti gat or will use cli nical 
j u d g me nt t o deter mi ne t he relati o ns hi p.

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, 
e vi de nce, a n d/ or ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a 
relati o ns hi p ca n n ot be r ule d out.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Assess me nt of C a us alit y

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 ha ve re vie we d t he A E or S A E a n d ha v e pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be 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 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or 
re p orti n g p ur p oses, as defi ne d b y  t he s p o ns or. I n a d diti o n, if t he i n vesti gat or 
deter mi nes t hat a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or 
m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort 
s uc h a n assess me nt i n t he de dicate d sectio n of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
F oll o w - Up of A E s a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of 
s u p ple me ntal meas ure me nts a n d/ or e val uati o ns, as me dicall y i n dicate d or as 
re q ueste d by t he s p o ns or, t o el uci date t he nat ure a n d/ or ca usality of t he A E or 
S A E as f ull y  as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt hcare pr o vi ders .

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs , i ncl u di n g hist o pat h ol o g y.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
F oll o w - Up of A E s a n d S A Es

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 
h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A E s
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D C T

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic D C T (e g, e S A E or P S S A) .

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E 
re p ort f or m (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T 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 new data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves 
u p date d data o n a pre vi o usl y  re p orte d S A E after t he electr o nic D C T has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a t he C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is o ne of t he met h o d s t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y .

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, a n alter nati ve met h o d s h o ul d 
be use d, e g, sec ure d ( Tra ns p ort L a yer Sec urit y) or pass w or d-pr otecte d e mail. I f 
n o ne of t hese met h o ds ca n be use d, n otificati o n b y tele p h o ne is acce pta ble wit h a 
c o p y of t he C T S A E Re p ort F or m se nt by o ver ni g ht mail or c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
N o c o ntrace pti o n met h o ds are re q uire d f or male partici pa nts i n t his st u d y , as t he calc ulate d 
safety mar gi n is ≥1 0 0- f ol d bet wee n t he esti mate d mater nal e x p os ure d ue t o se mi nal tra nsfer 
a n d t he N O A E L f or seri o us ma nifestati o ns of de vel o p me ntal t o xicit y  i n n o ncli nical st u dies.
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 mit te d i n t he st u d y. 
A fe male partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g a n d at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d a grees t o use a hi g hly effecti ve c o ntrace pti ve met h o d (fail ure rate of 
< 1 % per ye ar) d uri n g t he i nter ve nti o n peri o d a n d f or at least 2 8 d a 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). If a hi g hl y effecti ve, 
user -de pe n de nt met h o d is c h ose n, s he a grees t o c o nc urre ntl y use a n effect i ve barrier 
met h o d of c o ntrace pti o n. T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he 
c o ntrace pti ve met h o d i n relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
O R

Is a W O C B P a n d a grees t o use a hi g hly effecti ve (fail ure rate of < 1 % per year) 
u ser-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 on 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 ves ti gat or is res p o nsi ble f or re vie w of me dical hist or y, me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d 
pre g na nc y .
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
If fertilit y is u nclear (e g, a me n orr hea or oli g o me n orr hea ) a n d a me nstr ual c ycle ca n n ot be 
c o nfir me d bef ore t he first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y d ue t o a me dical ca use ot her t ha n t he a b o ve
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y  of t he a b o ve cate g ories ca n c o me fr o m t he site pers on nel’s 
re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y 
i nter vie w. T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he partici pa nt’s me dical 
rec or d f or t he st u dy.
2.
P ost me n o pa usal fe male .

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A h i g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars ol d a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A f e male on 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 o st 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.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 dit i 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 *

Tra ns der mal + b arrier *
7.
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:

Oral + b arrier *

I njecta ble + b arrier *
Se x ual A bsti ne nce
8.
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y an d t he preferre d a n d us ual lifest yl 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 6
1 0. 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 vatio 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 i s 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 
partici pa nt ’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa n ts w h o prese nt 
wit h t he f oll o wi n g la b orat or y  a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI 
( Hy’s la w) cases t o defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

Partici pa nt s wit h A S T/ A L T a n d T b ili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A LT val ues ≥3 × U L N A N D a T b ili val ue ≥2 × U L N 
wit h n o e vi de nce of he m ol y sis a n d a n al kali ne p h os p hatase val ue < 2 × U L N or n ot 
a vaila ble.

F or partici pa nt s wit h baseli ne A S T O R A L T O R T b ili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T 
val u es ≥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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T h e 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 dditi o n t o re peati n g meas ure me nts of A S T a n d A L T 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, incl u di n g rele va nt i nf or mati o n, 
s uc h as re vie w of et ha n ol, aceta mi n o p he n/ paraceta m ol (eit her by itself or as a c of or m ulate d 
pr o d uct i n prescri pti o n or o ver -t he-c o u nter me dicati o ns), recreati o nal dr u g, or s u p ple me nt 
( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact 
wit h a ja u n dice d pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d 
p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d. F urt her testi n g f or ac ute 
he patitis A, B, C, D, a n d E i nfecti o n , t otal bile aci ds, li ver i ma gi n g (e g, biliar y tract), a n d 
c ollecti o n of ser u m sa m ples f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct 
le vels ma y  be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y criteria of A S T/ A LT a n d 
T b ili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y’s la w) cases if n o 
ot her reas o n f or t he L F T a b n or malities has yet bee n f o u n d. S uc h p ote nti al DI LI ( H y’s l a w) 
c ases are t o be re p orte d as S A Es, irres pe cti ve of a v ail a bilit y of all t he res ults of t he 
i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 6. A p pe n di x 6 : Ki d ne y S afet y: M o nit ori n g G ui deli nes
1 0. 6. 1. L a b or at or y Assess me nt of C h a n ge i n Ki d ne y F u ncti o n a n d Detecti o n of Ki d ne y 
I nj ur y
Sta n dar d ki d ne y  safet y m o nit ori n g re q uires assess me nt of baseli ne a n d p ost baseli ne Screat 
meas ure me nt t o esti mate ki d ne y f u ncti o n [ Screat -base d e G F R] or creati ni ne cleara nce 
[e Cr Cl]). O btai ni n g Scree ni n g or Baseli ne Sc ys a n d p ost baseli ne refle x Sc ys (if c o nfir me d 
Screat i ncrease ≥0. 3 m g/ d L ) ma kes it feasi ble t o disti n g uis h A KI fr o m DI CI . 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 c o nfir me d, t he n refle x Sc ys meas ure me nt is nee de d t o e na ble p ost -
baseli ne c o m paris o n of e G F R c ha n ges ( Screat o nl y - base d e G F R a n d c o m bi ne d Screat pl us 
Sc y s e G F R). 
Re gar dless of w het her ki d ne y  f u ncti o n m o nit ori n g tests are re q uire d as a r o uti ne safety 
m o nit ori n g pr oce d ure i n t he st u d y , if t he i n vesti gat or or s p o ns or dee ms it necessar y t o f urt her 
assess ki d ne y safet y a n d q ua ntif y ki d ne y f u ncti o n, t he n t hese test res ults s h o ul d be ma na ge d 
a n d f oll o we d per sta n dar d of care.
1 0. 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) 8
2 0 2 1 C K D -
E PI            
Scr e at O nl y
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤ 0. 7
N A
e G F R = 1 4 3 × ( Scr eat/ 0. 7)-0. 2 4 1  ×  ( 0. 9 9 3 8) A ge
Fe male
if > 0. 7
N A
e G F R = 1 4 3 × ( 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 × ( Scr eat/ 0. 9)-0. 3 0 2  ×  ( 0. 9 9 3 8) A ge
Male
if > 0. 9
N A
e G F R = 1 4 2 × ( Scr eat/ 0. 9)-1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI           
Scr e at-Sc ys 
C o m bi ne d
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤ 0. 7
if ≤ 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Fe male
if ≤ 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Fe male
if > 0. 7
if ≤ 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Fe male
if > 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Male
if ≤ 0. 9
if ≤ 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Male
if ≤ 0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Male
if > 0. 9
if ≤ 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×  ( Sc ys/ 0. 8) - 0. 3 2 3  × ( 0. 9 9 6 1) A ge
Male
if > 0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×  ( Sc ys/ 0. 8) - 0. 7 7 8  × ( 0. 9 9 6 1) A ge
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 3. 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 ncti o n d ue t o 
eit her Ac ute or 
C hr o nic Ki d ne y 
I nj ur y 
A d ult 
partici pa nts
e G F R 
( 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 -o nset ty pe I sec o n d - de gree ( We nc ke bac h) A V b l oc k of >3 0- sec o n d d urati o n.

Fre q ue nt P V Cs, tri plets, or s h ort i nter vals ( < 3 0 sec o n ds) of c o nsec uti ve 
ve ntric ular c o m ple xes .
E C G Fi n di n gs T h at M a y Q u alif y as S A Es

Q Tc F pr ol o n gati o n > 5 0 0 ms .

A bs ol ute val ue of Q Tc F > 4 5 0 ms A N D Q Tc F c ha n ge fr o m baseli ne > 6 0 ms.

Ne w S T -T c ha n ges s u g gesti ve of m y ocar dial isc he mia .

Ne w - onset L B B B ( Q R S c o m ple x > 1 2 0 ms) .

Ne w -o nset 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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) .

V e ntric ular rh y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (H R
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m [s uc h as
torsa des de p oi ntes ]).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d -de gree) h eart b l oc k.
E C G 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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 8. A p pe n di x 8 : Dr u g Pr o d uct Acce pt a bilit y Q uesti o n n aire
C E N T E R
P A R TI CI P A N T I D
Pr ot oc ol I D:  C 5 0 9 1 0 1 3
Visit:  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
D A T E O F 
VI S IT
-
-
D D
M M M
Y Y Y Y
D R U G P R O D U C T A C C E P T A BI LI T Y Q U E S TI O N N AI R E

( 1) N O T D O N E
La n g ua ge a d mi nistere d:     
E n glis h 
Dr u g Pr o d uct Acce pt a bilit y Q uesti o n n aire
I N S T R U C TI O N S T O SI T E: T his q uesti o n naire s h o ul d be distri b ute d t o a n d fille d o ut b y 
partici pa nts i m me diatel y after ha vi n g ta ke n t he st u d y pr o d uct o n Da y 1, eac h peri o d.
Please as k t he partici pa nt t o vie w t he ta blets i n t he c u p wit h o ut t o uc hi n g t he m bef ore 
i n gesti n g t he st u dy pr o d uct a n d bef ore c o m pleti n g t he q uesti o n naire.
Please c ollect t he q uesti o n n aire w he n c o m plete. Please c o nfir m t hat t he q uesti o n naire is 
c o m plete. If t here are missi n g ite ms, please ret ur n t he q uesti o n naire t o t he partici pa nt a n d as k 
t he m t o c o m plete t he missi n g ite ms.
Please rec or d t he f oll o wi n g i nf or mati o n:
St u d y #/ St u d y Site
Peri o d a n d D a y
C ollect D ate
C ollect T i me
P artici p a nt I D ( R a n d I D)
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 n aire F ull y C o m plete d (circle)
Yes/ N o
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
C E N T E R
P A R TI CI P A N T I D
Pr ot oc ol I D:  C 5 0 9 1 0 1 3
Visit: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
D A T E O F 
VI S IT
-
-
D D
M M M
Y Y Y Y
D R U G P R O D U C T A C C E P T A BI LI T Y Q U E S TI O N N AI R E

( 1) N O T D O N E
La n g ua ge a d mi nistere d:     
E n glis h 
Dr u g - Pr o d uct Acce pt a bilit y Q uesti o n n aire
Please tell us h o w m uc h y o u a gree or disa gree wit h eac h of t he f oll o wi n g 1 4 state me nts b y 
circli n g t he n u m ber c orres p o n di n g t o y o ur a ns wer:
Str o n gl y 
A gree
A gree
Neit her 
A gree n or 
Dis a gree
Dis a gree
Str o n gl y 
Dis a gree
1.
T he s urface of t he ta blets l o o ke d r o u g h 
( n ot s m o ot h)
1
2
3
4
5
2.
T he ta blets ha d a n o d d s ha pe ( n ot r o u n d, 
o val, or ca ps ule -s ha pe d)
1
2
3
4
5
3.
T he c ol or of t he ta blets was n ot attracti ve
1
2
3
4
5
4.
T he ta blets felt c hal k y or r o u g h i n m y 
m o ut h
1
2
3
4
5
5.
T he ta blets st uc k t o t he i nsi de of m y 
m o ut h
1
2
3
4
5
6.
T he ta blets felt wa x y i n m y m o ut h
1
2
3
4
5
7.
T he ta blets be ga n t o diss ol ve i n m y 
m o ut h bef ore I s wall o we d t he m
1
2
3
4
5
8.
T he ta blets taste d bitter
1
2
3
4
5
9.
T he ta blets ha d a s mell
1
2
3
4
5
1 0. W he n I t o o k t he ta blets, I ha d a b ur ni n g 
se nsati o n i n m y m o ut h or o n m y t o n g ue
1
2
3
4
5
1 1. W he n I t o o k t he ta blets, I ha d a b ur ni n g 
se nsati o n i n m y t hr oat
1
2
3
4
5
1 2. T he ta blets w ere t o o bi g t o s wall o w
1
2
3
4
5
1 3. T he ta blets w ere diffic ult t o s wall o w
1
2
3
4
5
1 4. O verall, t hese ta blets were diffic ult t o 
ta ke
1
2
3
4
5
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 9. A p pe n di x 9 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y be use d i n t he pr ot oc ol.
A b bre vi ati o n
Ter m
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 E SI
a d verse e ve nt of s pecial i nterest
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A R D S
ac ute res pirat or y distress s yn dr o me
A S T
as partate a mi n otra nsferase
A U C 2 4
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 t o t he 
ti me 2 4 h o urs
A U C i nf
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 
e xtra p olate d t o i nfi nit y
A U C last
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 t o t he 
ti me of t he last q ua ntifia ble c o nce ntrati o n ( Clast)
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
β -h C G
β -h u ma n c h ori o nic g o na d otr o pi n
BI D
t wice daily
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
B S A
b o d y  s urface area
B U N
bl o o d urea nitr o ge n
C 1 2
c o nce ntrati o n at 1 2 h n o mi nal ti me p ost -d ose
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
C L / F
a p pare nt cleara nce
C last
last q ua ntifia ble c o nce ntrati o n
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
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
C T
cli nical trial
C TI S
Cli nical Trial I nf or mati o n S y ste m
C T M S
Cli nical Trial Ma na ge me nt S y ste m
C Y P
c yt oc hr o me P 4 5 0
C V
car di o vasc ular
D C T
data c ollecti o n t o ol
D DI
dr u g -dr u g i nteracti o n 
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 MI D
d osa ge m aterial ide ntificati o n
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 G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
e S A E
electr o nic seri o us a d verse e ve nt
E T
earl y ter mi nati o n
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli nical Trials 
( E ur o pea n Cli nical Trials Data base)
F D A 
U S F o o d a n d Dr u g A d mi nistrati o n
fm
fracti o n meta b olize d
F S H
f ollicle-sti m ulati n g h or m o ne
fu
fracti o n u n b o u n d
F/ U
f oll o w-u p
G 1 t o G 5
K DI G O e G F R cate g or y sta n dar dizati o n
G C P
G o o d Cli nical Practice
G D
gestati o n da y
G F R
gl o mer ular filtrati o n rate
G G T
ga m ma -gl uta m y l tra nsferase
G L P
G o o d La b orat or y  Practice
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C o V -2 2 9 E
h u ma n c or o na vir us 2 2 9 E
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
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
H R / hr
heart rate / h o ur ( base d o n t he c o nte nt)
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 C5 0
i n hi bit or y c o nce ntrati o n 5 0 %
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 ni zati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use
I D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal Ne w Dr u g 
I N R
i nter nati o nal n or malize d rati o
I P
i n vesti gati o nal pr o d uct 
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I RB
I nstit uti o nal Re vie w B oar d
I V
intra ve n o us (ly)
K
Pr o p orti o nalit y  c o nsta nt f or Sc h wartz E q uati o ns ( ki d ne y f u ncti o n)
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
k el
first-or der eli mi nati o n rate c o nsta nt
Ki
i n hi biti o n c o nsta nt
L B B B
left b u n dle bra nc h bl oc k
L F T
li ver f u ncti o n test
M A D
m ulti ple asce n di n g d ose
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M E
Meta b olis m a n d E xcreti o n
M E R S -C o V
mi d dle east res pirat or y  s yn dr o me c or o na vir us
M
Pr o
mai n pr otease
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
N H P
n o n -h u ma n pri mates
NI M P
n o n -i n vesti gati o nal me dici nal pr o d uct
N O A E L
n o o bser ve d a d verse effect le vel
P E
p h y sical e xa mi nati o n
PI
pri nci pal i n vesti gat or
PI M S
P hase 1 Ma na ge me nt S yste m
P K
p har mac o ki netic(s)
P R
p ulse rate
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
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 R S
A c o m bi nati o n of t hree of t he gra p hical deflecti o ns see n o n a t y pical 
electr ocar di o gra m
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 A
relati ve bi oa vaila bility
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
R R
resti n g rate
R R C K
Ral p h R uss ca ni ne ki d ne y cells R R C K
S A E
seri o us a d verse e ve nt
S A D
si n gle asce n di n g d ose
S A P
Statistical A nal y sis Pla n
S A R S -C o V -2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
S A R S -C o V -2 M pr o
t he mai n pr otease of S A R S-C o V -2
Scr
ser u m creati ni ne
Screat
ser u m creati ni ne 
Sc y s
ser u m c ystati n C
S D
si n gle d ose
S D D
s pra y drie d dis persi o n
S o A
sc he d ule of acti vities
S O P
sta n dar d o perati n g pr oce d ure
S R S D
Si n gle Refere nce Safet y D oc u me nt
S T -T
S T -se g me nt a n d T -wa ve
S U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n
t½
ter mi nal half-life
T bili
t otal bilir u bi n
T E A E
treat me nt e mer ge nt a d verse e ve nt
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me f or Cma x
U L N
u p per li mit of n or mal
U S
U nite d States
U TI
uri nar y  tract i nfecti o n
U V -V is
ultra vi olet -visi ble s pectr osc o p y
V ss
stea d y-state v ol u me of distri b uti o n ( = C L· M R T)
V z/ F
a p pare nt v ol u me of distri b uti o n
W B C
w hite bl o o d cell
W H O
W orl d Healt h Or ga nizati o n
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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 1 3
Fi nal Pr ot oc ol, 2 4 A u g ust 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 1. R E F E R E N C E S
1.
W H O Sit uati o n Re p ort 5 1. 1 1 Marc h 2 0 2 0. A vaila ble fr o m: 
htt ps:// w w w. w h o.i nt/e mer ge ncies/ diseases/ n o vel -c or o na vir us -2 0 1 9/sit uati o n -re p orts.
Accesse d: 2 9 Marc h 2 0 2 0. W H O Sit uati o n Re p ort 5 1. 1 1 Marc h 2 0 2 0. A vaila ble 
fr o m: htt ps:// w w w. w h o.i nt/e mer ge ncies/ diseases/ n o vel -c or o na vir us -2 0 1 9/sit uati o n -
re p orts. Accesse d: 2 9 Marc h 2 0 2 0.
2.  
W u Z, Mc G o o ga n J. C haracteristics of a n d i m p orta nt less o ns fr o m t he c or o na vir us 
disease 2 0 1 9 ( C O VI D -1 9) o ut brea k i n C hi na: s u m mar y  of a re p ort of 7 2, 3 1 4 cases 
fr o m t he C hi nese Ce nter f or Disease C o ntr ol a n d Pre ve nti o n. J A M A 
2 0 2 0; 3 2 3( 1 3): 1 2 3 9 - 4 2.
3. 
Ric har ds o n S, Hirsc h J, Narasi m ha n M, et al. Prese nti n g c haracteristics, 
c o m or bi dities, a n d o utc o mes a m o n g 5 7 0 0 patie nts h os pitalize d wit h C O VI D - 1 9 i n t he 
Ne w Y or k Cit y area. J A M A. 2 0 2 0; 3 2 3( 2 0): 2 0 5 2 - 9.
4.
D oc hert y A, Harris o n E, Gree n C, et al. Feat ures of 2 0 -1 3 3 U K patie nts i n h os pital 
wit h c o vi d- 1 9 usi n g t he I S A RI C W H O Cli nical C haracterisati o n Pr ot oc o l: 
pr os pecti ve o bser vati o nal c o h ort st u d y . B MJ. 2 0 2 0; 3 6 9: 1-1 2: m 1 9 8 5.
5.  
Wa n g D, H u B, H u C, et al. Cli nical c haracteristics of 1 3 8 h os pitalize d patie nts wit h 
2 0 1 9 n o vel c or o na vir us -i nfecte d p ne u m o nia i n W u ha n, C hi na. J A M A. 
2 0 2 0; 3 2 3( 1 1): 1 0 6 1 - 9.
6.
Pei G, Z ha n g Z , Pe n g J, et al. Re nal I n v ol ve me nt a n d Earl y Pr o g n osis i n Patie nts wit h 
C O VI D -1 9 P ne u m o nia. J A m S oc Ne p hr ol. 2 0 2 0; 3 1( 6): 1 1 5 7 - 6 5.
7.  
N o p p S, M oi k F, Jil ma B, et al. Ris k of ve n o us t hr o m b oe m b olis m i n patie nts wit h 
C O VI D - 1 9: A sys te matic re vie w a n d meta-a nal ys is. Res Pract T hr o m b Hae m ost. 
2 0 2 0; 4( 7): 1 1 7 8 - 9 1.
8.
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 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)

D o c u m e nt A p pr o v al R e c or d
D o c u m e nt N a m e:
D o c u m e nt Titl e:
Si g n e d B y:
D at e( G M T)
Si g ni n g C a p a cit y
0 9 0 1 7 7 e 1 9 e 6 3 e 1 a a\ A p pr o v e d\ A p pr o v e d O n: 2 4- A u g- 2 0 2 3 1 9: 1 8 ( G M T)
P P D
P P D
P P D