Clinical trial NCT06122194
Conditions: Healthy
Sponsor: Pfizer
Start date: 2023-11-23; Completion date: 2024-01-12
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to estimate the oral bioavailability of 3 new formulations of PF-07817883 (test) relative to reference tablet formulation in healthy adult participants under fasted conditions. The study will also assess the safety and tolerability of test and reference tablet formulations in healthy adult participants.

Detailed description:
This is a Phase 1, open-label, randomized, 4-period, 4-sequence crossover study in healthy adult participants evaluating the rBA of 3 new PF-07817883 test oral formulation(s) compared to PF-07817883 reference oral formulation. Approximately 12 participants will be enrolled in this study with approximately equal number of participants randomized to 1 of 4 sequences.

Arms: arm 1: Single oral dose of PF-07817883 tablet under fasted condition arm 2: Single oral dose of PF-07817883 tablet under fasted condition arm 3: Single oral dose of PF-07817883 tablet under fasted condition arm 4: Single oral dose of PF-07817883 tablet under fasted condition
Interventions: intervention 1: Drug: PF-07817883
Intervention descriptions: intervention 1: PF-07817883 tablet

Protocol documents:
Prot_000.pdf: 
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)
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