A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Crossover, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of PF-07853578 Administered to Healthy Adult Participants
Phase: PHASE1
Conditions: Healthy Participants
Sponsor: Pfizer

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A P H A S E 1, R A N D O MI Z E D, D O U B L E -B LI N D, S P O N S O R -O P E N, 
P L A C E B O -C O N T R O L L E D, C R O S S O V E R, FI R S T -I N-H U M A N S T U D Y T O 
E V A L U A T E T H E S A F E T Y, T O L E R A BI LI T Y, A N D P H A R M A C O KI N E TI C S O F 
SI N G L E A S C E N DI N G O R A L D O S E S O F P F - 0 7 8 5 3 5 7 8 A D MI NI S T E R E D T O 
H E A L T H Y A D U L T P A R TI C I P A N T S
St u d y I nter ve nti o n N u m ber :
P F - 0 7 8 5 3 5 7 8
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 5 7 3 7
E u dr a C T /E U C T N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 1 6 1 0 0 1
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A St u d y  t o Lear n A b o ut t he St u d y Me dici ne P F- 0 7 8 5 3 5 7 8 a n d H o w It Act s
i n t he B o dies of Healt h y A d ults
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nt s, yo u a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or 
use it f or u na ut h orize d p ur p oses. I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3 )
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 1
0 6 J u ne 2 0 2 3
Ori gi nal pr ot oc ol
1 8 A pril 2 0 2 3
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs a n d a n y pr ot oc ol a d mi nistrati ve c ha n ge
letter(s).
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
A m e n d me nt 1 ( 0 6 J u ne 2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt: T he pr ot oc ol is bei n g a me n de d t o re vise t he h u ma n
e x p os ure st o p pi n g li mits per F D A fee d bac k. T he h u ma n e x p os ure st o p pi n g li mits will be 
base d o n t otal e x p os ures a t t he N O A E L i n d o gs i n t he 2-wee k G L P t o xicit y st u d y a n d will 
n ot be c orrecte d f or s pecies -de pe n de nt pr otei n bi n di n g .
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
S u bst a nti al M o dific ati o n(s)
T he t otal C ma x a n d t otal 
A U C 2 4 h u ma n e x p os ure 
st o p pi n g li mits f or 
P F -0 7 8 5 3 5 7 8 were c ha n ge d 
t o 
 n g/ m L a n d  
 
n g• h/ m L, 
.
F D A re q ueste d t o set t he 
t otal h u ma n P K e x p os ure 
li mits t o t he t otal e x p os ures 
o bser ve d at t he N O A E L i n 
t he d o g.
Secti o n 4. 3. 3 ( H u ma n 
E x p os ure St o p pi n g L i mits), 
4. 3. 4 ( Rati o nale f or D ose 
Selecti o n), a n d 6. 6. 1 ( D ose 
Escalati o n a n d St o p pi n g 
R ules).
N o n -s u bst a nti al M o dific ati o n(s)
U p date d brief title. 
T he brief title was u p date d 
t o be c o nsiste nt wit h t he 
brief title o n 
cli nicaltrials. g o v.
Title pa ge a n d Secti o n 1. 1 
( S yn o psis)
C ha n ge d bl o o d press ure a n d 
p ulse rate meas ure me nts. 
Bl o o d press ure a n d p ulse 
rate meas ure me nts were 
u p date d per i nter nal 
g ui da nce t o facilitate 
e x p os ure -res p o nse 
m o deli n g.
Secti o n 1. 3 ( Sc he d ule of 
Acti vities)
U p date d t he i n dicati o n of 
P F - 0 7 8 5 3 5 7 8.
I n dicati o n of P F - 0 7 85 3 5 7 8 
was u p date d t o be c o nsiste nt 
wit h I N D a n d C D P 
d oc u me nts.
Secti o n 1. 1 ( S y n o psis) , 
Secti o n 2 (I ntr o d ucti o n) ,
Secti o n 2. 3. 3 ( O verall 
Be nefit/ Ris k C o ncl usi o n )
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3 )
Pa ge 3
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
Re m o ve d re d u n da nt te xt 
re gar di n g i nterlea vi n g 
c o h ort desi g n.
Clarificati o n
Secti o n 4. 2 ( Scie ntific 
Rati o nale f or St u d y  Desi g n)
Clarifie d te xt re gar di n g 
water c o ns u m pti o n w he n 
d osi n g u n der fe d c o n diti o n.
Clarificati o n
Secti o n 5. 3. 2 ( Meals a n d 
Dietar y  Restricti o ns)
A d de d te xt re gar di n g 
e xte m p ora ne o us d ose 
pre parati o n .
Clarificati o n
Secti o n 6. 2. 1 ( Pre parati o n 
a n d Dis pe nsi n g)
Re m o ve d re d u n da nt te xt 
re gar di n g p hys ical 
e xa mi nati o n.
Clarificati o n
Secti o n 8. 3. 1 ( P h y sical 
E xa mi nati o ns)
Mi n or gra m matical c ha n ges.
Clarificati o n
Secti o n 1. 1 ( S y n o psis) , 
Secti o n 4. 2 ( Scie ntific 
Rati o nale f or St u d y  Desi g n) ,
Secti o n 1 0. 7. 1 ( La b orat or y 
Assess me nt of C ha n ge i n 
Ki d ne y  F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y ),
Secti o n 1 0. 1 0 ( A p pe n di x 
1 0)
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 .....................................................................................................................9
LI S T O F FI G U R E S ................................................................................................................... 9
1. P R O T O C O L  S U M M A R Y................................................................................................... 1 0
1. 1. S y n o psis .................................................................................................................. 1 0
1. 2. Sc he ma .................................................................................................................... 1 5
1. 3. Sc he d ule of Acti vities ............................................................................................. 1 6
2. I N T R O D U C TI O N ............................................................................................................... 2 0
2. 1. St u d y  Rati o nale....................................................................................................... 2 0
2. 2. Bac k gr o u n d ............................................................................................................. 2 0
2. 2. 1. P N P L A 3 a n d N A F L D/ N A S H ..................................................................... 2 0
2. 2. 2. N o ncli nical P har mac ol o g y .......................................................................... 2 0
2. 2. 3. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 2 1
2. 2. 4. 
....................................................................................... 2 2
2. 2. 5. N o ncli nical Safet y ...................................................................................... 2 2
2. 3. Be nefit/ Ris k Assess me nt ......................................................................................... 2 2
2. 3. 1. Ris k Assess me nt ......................................................................................... 2 4
2. 3. 2. Be nefit Assess me nt ..................................................................................... 2 6
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................ 2 6
3. O BJ E C TI V E S A N D E N D P OI N T S ..................................................................................... 2 6
4. S T U D Y D E SI G N ................................................................................................................. 2 6
4. 1. O verall Desi g n ......................................................................................................... 2 6
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n..................................................................... 2 8
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts ......................................... 2 9
4. 3. J ustificati o n f or D ose ..............................................................................................2 9
4. 3. 1. H u ma n P K Pre dicti o ns ............................................................................... 3 0
4. 3. 2. Pre dicte d Efficaci o us C o nce ntrati o n a n d H u ma n D ose .............................. 3 0
4. 3. 3. H u ma n E x p os ure St o p pi n g L i mits..............................................................3 0
4. 3. 4. Rati o nale f or D ose Selecti o n ......................................................................3 0
4. 4. E n d of St u d y  Defi niti o n .......................................................................................... 3 2
5. S T U D Y P O P U L A T I ON ......................................................................................................3 2
5. 1. I ncl usi o n Criteria ..................................................................................................... 3 2
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 2. E xcl usi o n Criteria ....................................................................................................3 3
5. 3. L ifest yle C o nsi derati o ns..........................................................................................3 5
5. 3. 1. C o ntrace pti o n ..............................................................................................3 5
5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................3 5
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................3 7
5. 3. 4. Acti vit y .......................................................................................................3 7
5. 4. Scree n Fail ures ........................................................................................................3 7
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 8
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................3 8
6. 1. 1. A d mi nistrati o n ............................................................................................3 9
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................4 0
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................4 1
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................4 1
6. 4. Bli n di n g................................ ...................................................................................4 1
6. 4. 1. Bli n di n g of Partici pa nts ..............................................................................4 1
6. 4. 2. Bli n di n g of Site Pers o n nel ..........................................................................4 2
6. 4. 3. Bli n di n g of t he S p o ns or.............................................................................. 4 2
6. 4. 4. Se nsiti ve Cli nical Data ...............................................................................4 2
6. 4. 5. Brea ki n g t he Bli n d ......................................................................................4 2
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................4 3
6. 6. D ose M o dificati o n ...................................................................................................4 3
6. 6. 1. D ose Escalati o n a n d St o p pi n g R ules ..........................................................4 4
6. 7. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he St u d y ......................4 5
6. 8. Treat me nt of O ver d ose................................ ............................................................4 5
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................4 5
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................4 6
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................4 6
7. 1. 1. P ote ntial Cases of Ac ute Ki d ne y  Inj ur y .....................................................4 6
7. 1. 2. E C G C ha n ges ..............................................................................................4 8
7. 1. 3. C O VI D - 1 9 ..................................................................................................4 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 .......................................4 8
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 2. 1. Wit h dra wal of C o nse nt ...............................................................................4 9
7. 3. L ost t o F oll o w -U p ...................................................................................................4 9
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S................................ ...............................5 0
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures .................................................................5 0
8. 2. Efficac y  Assess me nts..............................................................................................5 1
8. 3. Safet y Assess me nts .................................................................................................5 1
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 2
8. 3. 2. Ne ur ol o gical E xa mi nati o ns ........................................................................5 2
8. 3. 3. Vital Si g ns ..................................................................................................5 2
8. 3. 3. 1. Bl o o d Press ure a n d P ulse Rate ..................................................5 2
8. 3. 3. 2. Res pirat or y  Rate........................................................................5 3
8. 3. 4. Electr ocar di o gra ms..................................................................................... 5 3
8. 3. 4. 1. C o nti n u o us Car diac M o nit ori n g b y Tele metr y .........................5 4
8. 3. 5. Cli nical Safet y  La b orat or y Assess me nts....................................................5 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 .................5 5
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......5 5
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................5 6
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 5 6
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................5 7
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................5 7
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................5 7
8. 4. 5. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure .....................................................5 7
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................5 8
8. 4. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................5 9
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................6 0
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................6 0
8. 4. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ..............................................................................6 0
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 6 0
8. 4. 8. 1. Lac k of Efficac y ........................................................................6 0
8. 4. 9. Me dical De vice Deficie ncies ......................................................................6 0
8. 4. 1 0. Me dicati o n Err ors .....................................................................................6 0
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 5. P har mac o ki netics ....................................................................................................6 1
8. 6. G e netics ...................................................................................................................6 2
8. 6. 1. S pecifie d Ge netics ......................................................................................6 2
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics................................................... 6 3
8. 7. Bi o mar kers ..............................................................................................................6 3
8. 7. 1. S pecifie d Ge ne E x pressi o n ( R N A) Researc h .............................................6 3
8. 7. 2. S pecifie d Pr otei n Researc h .........................................................................6 3
8. 7. 3. S pecifie d Meta b ol o mic Researc h ...............................................................6 4
8. 7. 4. Retai ne d Researc h Sa m ples f or Bi o mar kers ...............................................6 4
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................6 4
8. 9. Healt h Ec o n o mics ...................................................................................................6 4
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................6 4
9. 1. Statistical H y p ot hesis ..............................................................................................6 4
9. 2. A nal y sis Sets ...........................................................................................................6 4
9. 3. Stati stical A nal yses .................................................................................................6 5
9. 3. 1. Safet y A nal ys es ..........................................................................................6 5
9. 3. 1. 1. Electr ocar di o gra m A nal y ses......................................................6 6
9. 3. 2. P K E n d p oi nts ..............................................................................................6 6
9. 3. 2. 1. Deri vati o n of P F -0 7 8 5 3 5 7 8 P K Para meters ..............................6 6
9. 3. 2. 2. Statistical Met h o ds f or P K Data................................ ................6 7
9. 3. 3. Tertiar y / E x pl orat or y E n d p oi nt(s) A nalys is ................................................6 8
9. 3. 4. Ot her A nal ys es ............................................................................................6 8
9. 4. I nteri m A nal ys es .....................................................................................................6 8
9. 5. Sa m ple Size Deter mi nati o n .....................................................................................6 8
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ..........................................................................6 9
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............6 9
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................6 9
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................6 9
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................7 0
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................7 0
1 0. 1. 4. Data Pr otecti o n .........................................................................................7 1
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 0. 1. 5. C o m mittees Str uct ure ...............................................................................7 1
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ...................................................7 1
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ......................................................7 1
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................7 2
1 0. 1. 8. S o urce D oc u me nts ....................................................................................7 4
1 0. 1. 9. Use of Me dical Rec or ds ............................................................................7 4
1 0. 1. 1 0. St u d y  a n d Site Start a n d Cl os ure ............................................................7 5
1 0. 1. 1 1. P u blicati o n P olic y ...................................................................................7 5
1 0. 1. 1 2. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................7 6
1 0. 2. A p pe n di x 2: Cli n ical La b orat or y Tests.................................................................7 7
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -U p, a n d Re p orti n g ..................................................................... 8 0
1 0. 3. 1. Defi niti o n of A E .......................................................................................8 0
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................8 1
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w- U p of A Es a n d/ or S A Es D uri n g 
t he Acti ve C ollecti o n Peri o d............................................................................8 2
1 0. 3. 4. Re p orti n g of S A Es.................................................................................... 8 6
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................8 7
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 8 7
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl us i o n Criteria.................................8 7
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................8 7
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................8 8
1 0. 5. A p pe n di x 5: Ge netics ............................................................................................9 0
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts .......9 1
1 0. 7. A p pe n di x 7: Ki d ne y  Safet y: M o nit ori n g G ui deli nes ............................................9 3
1 0. 7. 1. La b orat or y Assess me nt of C ha n ge i n Ki d ne y F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y ..............................................................................9 3
1 0. 7. 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...............9 3
1 0. 7. 2. 1. A d ults ( 1 8 Years a n d A b o ve) – 2 0 2 1 C K D - E PI 
E q uati o ns................................ ...........................................................9 3
1 0. 7. 3. Ki d ne y  F u ncti o n Calc ulati o n T o ols..........................................................9 3
1 0. 7. 4. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ...................................................................................................9 4
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3 )
Pa ge 9
1 0. 8. A p pe n di x 8: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ...................................9 5
1 0. 9. A p pe n di x 9: Pr o h i bite d C o nc o mita nt Me dicati o ns T hat Ma y Res ult i n D DI.......9 7
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns ...............................................................................9 9
1 1. R E F E R E N C E S ................................................................................................................1 0 4
LI S T O F T A B L E S
Ta ble 1.
St u d y  Sc he d ule of Assess me nts................................................................1 6
Ta ble 2.
St u d y  Sc he d ule of Assess me nts f or P K, Vitals, a n d E C Gs o n Da y  1 
of Eac h Peri o d ...........................................................................................1 9
Ta ble 3.
Pre dicte d H u ma n E x p os ures, Pr ojecte d Li ver P N P L A 3 Re d ucti o n, 
a n d Safet y Mar gi ns at Pr o p ose d Si n gle D oses of P F - 0 7 8 5 3 5 7 8..............3 1
Ta ble 4.
Plas ma P F -0 7 8 5 3 5 7 8 P K Para meters .......................................................6 6
Ta ble 5.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts.............................................7 8
LI S T O F FI G U R E S
Fi g ure 1.
St u d y  Desi g n: I nterlea vi n g, Place b o-C o ntr olle d, 4 -Peri o d, 
Cr oss o ver Desi g n ......................................................................................1 5
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: A P hase 1, Ra n d o mize d, D o u ble -Bli n d, S p o ns or -O pe n, Place b o -C o ntr olle d, 
Cr oss o ver, First -i n-H u ma n St u d y  t o E val uate t he Safet y, T olera bility, a n d P har mac o ki netics 
of Si n gle Asce n di n g Oral D oses of P F - 0 7 8 5 3 5 7 8 A d mi nistere d t o Healt h y A d ult Partici pa nts
Bri ef Title: A St u d y  t o Lear n A b o ut t he St u d y Me dici ne P F- 0 7 8 5 3 5 7 8 an d H o w It Act s i n 
the B o d ies of Healt h y A d ults
Re g ul at or y A ge nc y I de ntific ati o n N u m ber(s):
U S I N D N u m ber:
1 6 5 7 3 7
E u dr a C T /E U C T N u m ber:
N A
Cli nic al Tri als. g o v I D:
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 1 6 1 0 0 1
P h ase:
1
R ati o n ale : T his st u d y  is t he first cli nical st u d y wit h P F-0 7 8 5 3 5 7 8. T he safet y , t olera bility, 
a n d plas ma p har mac o ki netics ( P K ) of P F - 0 7 8 5 3 5 7 8 after a d mi nistrati o n of escalati n g, si n gle, 
oral d oses will be e val uate d.
O bjecti ves a n d E n d p oi nts :
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y:

T o e val uate t he safet y a n d t olera bilit y of si n gle 
asce n di n g d oses of P F - 0 7 8 5 3 5 7 8 a d mi nistere d orall y 
t o healt h y a d ult partici pa nts.

Assess me nt of A Es, cli nical safet y la b orat or y tests, vital 
si g ns, c o nti n u o us car diac m o nit ori n g, 1 2-lea d E C Gs, 
P Es a n d ne ur ol o gical e xa mi nati o ns.
Sec o n d ar y: 
Sec o n d ar y:

T o e val uate t he P K of P F -0 7 8 5 3 5 7 8 f oll o wi n g si n gle 
d oses of P F -0 7 8 5 3 5 7 8 a d mi nistere d orall y t o healt h y 
a d ult partici pa nts.

P K para meters deri ve d fr o m plas ma P F -0 7 8 5 3 5 7 8 
c o nce ntrati o ns: C ma x, Tma x , A U Clast, a n d if data per mit, 
A U C i nf, a n d t½ .
A b bre viati o ns: A E = a d verse e ve nt; A U C i nf = area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m ti me 0 
e xtra p olate d t o i nfi nite ; A U C last = area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o t he ti me of 
t he last q ua ntifia ble c o nce ntrati o n; C ma x = ma xi m u m plas ma c o nce ntrati o n; E C G = electr ocar di o gra m; P E =
p h ysical e xa mi nati o n; P K = p har mac o ki netic(s); t½ . = ter mi nal half -life; Tma x = ti me f or C ma x .
O ver all Desi g n : T his st u d y is a ra n d o mize d, i n vesti gat or- a n d partici pa nt -bli n d,
s p o ns or-o pe n, place b o -c o ntr olle d, first-i n-h u ma n ( FI H ), si n gle asce n di n g d ose, 4 -peri o d, 
cr oss o ver, i nterlea vi n g desi g n st u d y of P F -0 7 8 5 3 5 7 8 orall y  a d mi nistere d t o healt h y a d ult 
partici pa nts . Preca uti o nar y se nti nel d osi n g will be use d i n t his st u dy. T w o partici pa nts ( 1 
recei vi n g P F - 0 7 8 5 3 5 7 8 a n d 1 recei vi n g place b o) wit hi n a peri o d will be d ose d i nitiall y bef ore 
t he re mai ni n g partici pa nts of t hat peri o d are d ose d. Safet y a n d t olera bilit y data t hr o u g h at 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
least 2 4 h o urs p ost- d ose f or t he se nti nel partici pa nts will be re vie we d pri or t o d osi n g t he 
re mai ni n g partici pa nts of t hat peri o d. Se nti nel d osi n g ma y b e o mitte d w he n re peati n g a d ose 
le vel or a d mi nisteri n g a l o wer d ose le vel t ha n pre vi o usl y e val uate d.
N u m ber of P artici p a nts: A p pr o xi matel y  2 4 healt h y a d ult partici pa nts ( u p t o 3 c o h orts of 
a p pr o xi matel y 8 partici pa nts eac h) will be e nr olle d i n t he st u d y .
N ote: " E nr olle d" mea ns a partici pa nt's, or t heir le gall y a ut h orize d re prese ntati ve’s, a gree me nt 
t o partici pate i n a cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
ra n d o mizati o n t o st u d y i nter ve nti o n.
St u d y P o p ul ati o n : Ke y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
Partici pa nts m ust meet t he f oll o wi n g ke y  i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
1.
Male a n d fe male partici pa nts of n o n -c hil d beari n g p ote ntial a ge d 1 8 t o 6 5 years at 
scree ni n g w h o are o vertl y healt h y as deter mi ne d b y me dical e val uati o n i ncl u di n g 
me dical hist or y , p h y sical e xa mi nati o n, la b orat or y tests, a n d car diac m o nit ori n g. 
2.
B MI of 1 6 t o 3 0. 5 k g/ m 2; a n d a t otal b o dy wei g ht > 5 0 k g ( 1 1 0 l b).
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).
2.
A n y  me dical or psyc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/ be ha vi or or la b orat ory a b n or malit y 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.
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 or str o n g c yt oc hr o me P 4 5 0 3 A (C Y P 3 A )
i n d ucers or i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o 
t he first d ose of st u dy i nter ve nti o n. 
4.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y  i nter ve nti o n use d i n t his st u d y ( w hic he ver is l o n ger). Partici pati o n i n 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3 )
Pa ge 1 2
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d uri n g t heir 
partici pati o n i n t his st u d y .
5.
A p ositi ve uri ne dr u g test.
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 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.
7.
Re nal i m pair me nt as defi ne d b y  a n esti mate d gl o mer ular filtrati o n rate (e G F R ) of 
< 7 5 m L / mi n/ 1. 7 3 m². Base d u p o n partici pa nt a ge at scree ni n g, e G F R is calc ulate d 
usi n g t he c hr o nic ki d ne y disease e pi de mi ol o g y (C K D -E PI ) e q uati o ns t o deter mi ne 
eli gi bilit y a n d t o pr o vi de a baseli ne t o q ua ntif y a n y s u bse q ue nt ki d ne y safet y e ve nts. 
F or eli gi bilit y assess me nt base d u p o n esti mate d re nal f u ncti o n, t he hi g her of t he 
scree ni n g a n d baseli ne e G F R val ues ma y be use d.
8.
He mat uria as defi ne d b y > 1 + he me o n uri ne di pstic k.
9.
Al b u mi n uria as defi ne d b y al b u mi n/ creati ne (Cr ) rati o o n s p ot uri ne al b u mi n ( U A )
> 3 0 m g/ g.
1 0. Sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nically rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms, 
c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate- a ge m y o car dial i nfarcti o n, S T -T 
i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d - or t hir d - de gree 
atri o ve ntric ular (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 Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice 
a n d t he a vera ge of t he 3 Q Tc F or Q R S val ues use d t o deter mi ne t he partici pa nt’s 
eli gi bilit y. C o m p uter-i nter prete d E C Gs s h o ul d be o verrea d b y a p hys icia n 
e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt.
1 1. 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 nica l la b orat or y tests at 
scree ni n g, as assesse d by t he st u d y  s pecific la b orat or y a n d c o nfir me d by a si n gle 
re peat test, if dee me d necessar y: 

Ala ni ne a mi n otra nsferase (A L T ), as partate a mi n otra nsferase (A S T ), Bilir u bi n 
≥1. 0 5 × U L N. Partici pa nts wit h a n ele vate d t otal bilir u bi n c o nsiste nt wit h Gil bert’s 
Disease m a y ha ve a direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y  
pr o vi de d t he direct bilir u bi n le vel is ≤u p per li mit of n or mal (U L N ).

T otal c h olester ol, tri gl yceri des, or direct L D L ≥1. 2 5 × U L N.
1 2. 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 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 3. Use of t o bacc o or nic oti ne-c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nt of 
5 ci garettes/ da y or 2 c he ws of t o bacc o/d a y .
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. 
St u d y Ar ms a n d D ur ati o n: T he t otal d urati o n of partici pati o n fr o m t he scree ni n g visit 
t o t he tele p h o ne f oll o w-u p c o ntact will be a p pr o xi matel y  1 7 wee ks f or eac h partici pa nt.
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 5 3 5 7 8
Place b o
Use
E x peri me ntal
Place b o
I M P or NI M P/ A x M P
I M P
I M P
D ose F or m ul ati o n
B ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s ol uti o ns a n d 
s us pe nsi o ns
B ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s ol uti o ns a n d 
s us pe nsi o ns
U nit D ose Stre n gt h(s)
0. 1 -5 0 0 m g
0 m g
R o ute of 
A d mi nistr ati o n
Oral
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 ni n vesti gati o nal me dici nal pr o d uct.
St u d y Ar m(s)
Ar m Title
C o h ort 1
C o h ort 2
C o h ort 3 ( O pti o nal)
Ar m Descri pti o n
Partici pa nts will recei ve u p t o 
4 d ose le vels of P F -0 7 8 5 3 5 7 8 
a n d u p t o 2 d ose le vels of 
matc hi n g place b o. D oses will 
be a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns as 
escalati n g si n gle d oses t o be 
deter mi ne d.
Partici pa nts will recei ve u p 
t o 4 d ose le vel s of 
P F - 0 7 8 5 3 5 7 8 a n d u p t o 
2 d ose le vels of matc hi n g 
place b o. D oses will be 
a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns as 
escalati n g si n gle d oses t o be 
deter mi ne d.
Partici pa nts will recei ve u p 
t o 4 d ose le vels of 
P F - 0 7 8 5 3 5 7 8 a n d u p t o 
2 d ose le vels of m atc hi n g 
place b o. D oses will be 
a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns as 
escalati n g si n gle d oses t o be 
deter mi ne d.
Assess me nt of t he safet y,  t olera bilit y, a n d P K after eac h si n gle d ose le vel will be c o n d ucte d 
bef ore escalati n g t o t he ne xt d ose le vel. T he d ose/e x p os ure -escalati o n i ncre me nts are pla n ne d 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
t o be u p t o a p pr o xi mate se mi-l o garit h mic i ncreases i n e x p os ure fr o m t he pre vi o us hi g hest 
d ose le vel t hat has bee n e val uate d. T he act ual d ose le vels , tar get e x p os ures, a n d/ or d ose le vel 
i ncre me nts m a y  be a dj uste d d uri n g t he st u d y base d o n e mer gi n g h u ma n safet y, t olera bility, 
a n d P K data, b ut pr ojecte d e x p os ures will n ot e xc ee d t he pre defi ne d h u ma n e x p os ure li mits.
St atistic al Met h o ds : T he sa m ple size has bee n c h ose n base d o n t he nee d t o mi ni mize first 
e x p os ure t o h u ma ns of a ne w c he mical e ntit y a n d t he re q uire me nt t o c o n d uct a de q uate 
safety , t olerabilit y , a n d P K assess me nts at eac h d ose le vel. All safe t y a nal yses will be 
perf or me d o n t he safet y a nal ysis set, w hic h is defi ne d as 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 ud y i nter ve nti o n. Partici pa nts will be 
a nal yze d acc or di n g t o t he st u dy i nter ve nti o n t hey act uall y recei ve 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 ve ly,  w here 
a p pr o priat e. T he plas ma P K para meters f or P F -0 7 8 5 3 5 7 8 f oll o wi n g oral d ose a d mi nistrati o n 
wil l be deri ve d fr o m t he plas ma c o nce ntrati o n‑ti me pr ofiles. Plas ma P K para meters a n d 
c o nce ntrati o ns of P F -0 7 8 5 3 5 7 8 will be descri pti vel y s u m marize d b y d ose (a n d fasti n g 
c o n diti o n a n d f or m u lati o n, if a p pr o priate) a n d n o mi nal ti me, as a p pr o priat e.
Et hic al C o ns i der ati o ns: T he partici pa nts i n t his st u d y  are n ot e x pecte d t o o btai n a n y 
s pecific be nefit be yo n d c o ntri b uti n g t o t he pr ocess of de vel o pi n g ne w t hera pies i n a n area of 
u n met nee d. T he y will be e x pecte d t o c o m mit ti me a n d ma y  e x perie nce s o me disc o mf ort 
w hile u n der g oi n g st u d y pr oce d ures. H o we ver, t he y  will recei ve cl ose m o nit ori n g of t heir 
safety via safet y m o nit ori n g pr oce d ures (e g , p h y sical e xa mi nati o ns, 1 2-lea d E C Gs, vital 
si g ns) as o utli ne d i n t his pr ot oc ol. Base d o n t he t otalit y of a vaila ble n o ncli nical data, a n d 
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 o verall 
be nefit/ris k pr ofile s u p p orts cli nical testi n g of P F- 0 7 8 5 3 5 7 8 i n t his st u d y  as part of t he 
cli nical de vel o p me nt f or t he treat me nt of n o nalc o h olic steat o he pat itis (N A S H ) wit h li ver 
fi br osis i n patie nts w h o are carriers of t he P N P L A 3-1 4 8 M allele.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 2. Sc he m a
Fi g ure 1.
St u d y Desi g n : I nterle a vi n g, P l ace b o- Co ntr olle d, 4 - Peri o d, C r oss o ver D esi g n
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1. 3. S c he d ule of Acti v ities
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures. Refer t o t he S T U D Y A S S E S S M E N T S A N D 
P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he 
pr ot oc ol. 
T he i n vesti gat or ma y  sc hed ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d in t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well-bei n g of t he partici pa nt .
T a ble 1 .
St u d y Sc he d ule of Assess me nts
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble are i n A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 4
F oll o w -U p
E T
N otes
D a y s Rel ati ve t o D a y 1
D a y -2 8    
t o
D a y - 2
D a y 
- 1
D a y 
1
D a y
2
D a y 
3
D a y 
4
Visit:
D a y 
8- 1 1
C o nt act:
D a y
2 9- 3 6
F oll o w -u p c o ntact ma y occ ur via tele p h o ne c o ntact a n d 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. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
I nf or me d c o nse nt 
X
See Secti o n 1 0. 1. 3 f or a d diti o nal i nf or mati o n.
O ut patie nt visit
X
 
 
 

X
7- 1 0 da ys after t he fi nal d ose of s t u d y i nter ve nti o n ( Peri o d 4 o nl y)
I n patie nt sta y at C R U
X
 
 
 

X
Partici pa nts ma y be as ke d t o re mai n at t he C R U after c o m pleti o n of Da y 4 
acti vities at t he discreti o n of t he i n vesti gat or or if safet y, t olera bilit y, or P K data 
(e g, t½ is l o n ger t ha n e x pecte d) dictate t he nee d t o pr ol o n g c o nfi ne me nt i n t he 
C R U.
Disc har ge fr o m C R U
 
 
 

X
De m o gra p h y
X
 
 
 

I ncl u di n g hei g ht a n d wei g ht 
I ncl usi o n/e xcl usi o n 
criteria
X  
X
Da y -1 i n Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
Me dical/ me dicati o n 
hist or y
X  
X
Da y -1 i n Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
H ist or y of alc o h ol, 
t o bacc o, a n d ille gal dr u g 
use
X  
X
Da y -1 i n Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
Re vie w c o nc o mita nt 
treat me nts
X
 
 
 
 
 
 

X  
X
See Secti o n 6. 9 f or a d diti o nal i nf or mati o n.
C o ntrace pti o n c hec k 
X
X
X
X
X
X
C o ntrace pti ve g ui da nce is o utli ne d i n A p pe n di x 4 .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 .
St u d y Sc he d ule of Assess me nts
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble are i n A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 4
F oll o w -U p
E T
N otes
D a y s Rel ati ve t o D a y 1
D a y -2 8    
t o
D a y - 2
D a y 
- 1
D a y 
1
D a y
2
D a y 
3
D a y 
4
Visit:
D a y 
8- 1 1
C o nt act:
D a y
2 9- 3 6
F oll o w -u p c o ntact ma y occ ur via tele p h o ne c o ntact a n d 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. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
C O VI D -1 9 relate d
meas ures
X  
X
 
 
 

X  
X
X
Per C R U pr oce d ures.
Seri o us a n d n o nseri o us 
A E m o nit ori n g
X
 
 
 
 
 
 

X  
X
See Secti o n 8. 4. 3 f or f oll o w-u p A E a n d S A E assess me nts.
P h ysical e xa mi nati o n
X  
X
X
X
C o m plete P E at scree ni n g or u p o n a d missi o n f or a partici pa nt’s first peri o d i n t he 
st u d y. Ot her wise, brief P E perf or me d f or fi n di n gs d uri n g pre vi o us e xa m or 
ne w/ o pe n A Es, at i n vesti gat or discreti o n. See Secti o n 8. 3. 1 f or a d diti o nal details.
Ne ur ol o gical e xa mi nati o n
X
See  Ta ble 2
X
X
X
A d diti o nal e xa ms perf or me d at i n vesti gat or discreti o n. See Secti o n 8. 3. 2 f or 
a d diti o nal details.
Res pirat or y rate
X
X
S u pi ne B P  a n d p ulse rate
X
X  
X  
X  
X  
X
X
Si n gle s u pi ne bl o o d press ure a n d p ulse rate at scree ni n g, f oll o w-u p visit , a n d E T. 
Tri plicate s u pi ne bl o o d press ure a n d p ulse rate at all ot her ti mes. See Secti o n 8. 3. 3
f or a d diti o nal details.
1 2 -Lea d E C G
X
X  
X  
X  
X  
X
X
Si n gle 1 2 -lea d E C G at scree ni n g, f oll o w-u p visit , a n d E T. Tri plicates at all ot her 
ti mes. See Secti o n 8. 3. 4 f or a d diti o nal details.
C o nti n u o us car diac 
tele metr y
X
Baseli ne tele metr y t o be rec or de d f or at least 2 h o urs pri or t o t he first d ose i n 
Peri o d 1 o nl y. T his ma y be d o ne i m me diatel y pri or t o d osi n g or at s o me 2 -h o ur 
c o nti n u o us i nter val i n t he 2 4 h o urs pri or t o d osi n g, as l o n g as t he partici pa nt is 
a wa ke. P ost -d ose tele metr y will c o nti n ue f or 8 h o urs after d osi n g. See 
Secti o n 8. 3. 4. 1 f or a d diti o nal details. 
Bli n de d st u d y i nter ve nti o n 
a d mi nistrati o n
Sta n dar dize d meals/s nac k
X  
X
 

X
See Secti o n 5. 3. 2 .
Bl o o d s a m ples f or:
C li nical safet y la b tests, 
i ncl u di n g li pi d pa nel
X  
X  
X
X  
X
X
Partici pa nt s t o fast f or at least 1 0 h o urs pri or t o sa m ple c ollecti o n f or cli nical safet y 
la b tests. See S ecti o n 5. 3. 2 f or a d diti o nal details. Da y -1 res ults will be re vie we d 
a n d c o nfir me d acce pta ble pri or t o d osi n g.
S er u m F S H
X
O nl y f or p ost me n o pa usal w o me n .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 1 .
St u d y Sc he d ule of Assess me nts
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble are i n A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 4
F oll o w -U p
E T
N otes
D a y s Rel ati ve t o D a y 1
D a y -2 8    
t o
D a y - 2
D a y 
- 1
D a y 
1
D a y
2
D a y 
3
D a y 
4
Visit:
D a y 
8- 1 1
C o nt act:
D a y
2 9- 3 6
F oll o w -u p c o ntact ma y occ ur via tele p h o ne c o ntact a n d 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. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
H Bc A b, H Bs A g, H C V A b, 
HI V testi n g
X
See A p pe n di x 2 : Cli nical La b orat or y Tests. 
Retai ne d Researc h 
Sa m ple f or Ge netics 
(Pre p D 1 )
X
Pre p D 1 Retai ne d Researc h Sa m ples f or Ge netics: C ollecte d i n Peri o d 1 o nl y. If n ot 
c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at t he ne xt a vaila ble ti me p oi nt 
w he n bi os peci me ns are bei n g c ollecte d i n c o nj u ncti o n wit h a partici pa nt visit. T o 
be c ol lecte d as o utli ne d i n Secti o n 8. 6. 2 .
S pecifie d ge netics f or 
P N P L A 3
X
C ollecte d i n Peri o d 1 o nl y. If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect 
at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g c ollecte d i n 
c o nj u ncti o n wit h a partici pa nt visit. T o be c ollecte d as o utli ne d i n Secti o n 8. 6. 1 .
Retai ne d Researc h 
Sa m ple f or Bi o mar kers
(Pre p B 2. 5 )
See
Ta ble 2
X
T o be c ollecte d as o utli ne d i n Secti o n 8. 7. 4 .
P F -0 7 8 5 3 5 7 8 plas ma P K
X  
X  
X  
X
X 
See Secti o n 8. 5 f or a d diti o nal details.
Uri ne s a m ples f or:
Uri ne dr u g testi n g
X
X
Res ults of a n y pre -d ose testi n g t o be c o nfir me d acce pta ble pri or t o d osi n g.
Uri nal ysis ( wit h 
micr osc o p y, if nee de d)
X  
X  
X
X  
X
X
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 2 .
St u d y Sc he d ule of A ssess me nts f or P K, Vit als, a n d E C Gs o n D a y 1 of E ac h Peri o d
Visit I de ntifier 
A b bre viati o ns use d i n 
t his ta ble ma y be f o u n d 
i n A p pe n di x 1 0 .
Peri o d 1 t o Peri o d 4
N otes
D a y 1
H o urs Rel ati ve t o
D os i n g at 0 h o ur
-1. 0
-0. 5
0
0. 5
1
2
3
4
6
8
1 0
1 2
Da y 1 acti vities at ti me = 0 h o ur are pri or t o t he d ose, e xce pt f or st u d y i nter ve nti o n
a d mi nistrati o n .
Bli n de d s t u d y 
i nter ve nti o n
a d mi nistrati o n
X
Preca uti o nar y se nti nel d osi n g will be use d i n a n y peri o d e val uati n g escalati n g d oses of 
P F - 0 7 8 5 3 5 7 8. See Secti o n 4. 1 f or a d diti o nal details.
Partici pa nts s h o ul d fast f or at least 1 0 h o urs pri or t o d osi n g, e xce pt f or peri o ds i n 
w hic h f o o d effects are i n vesti gate d. See Secti o n 5. 3. 2 f or a d diti o nal i nf or mati o n .
Ne ur ol o gical e xa m
 
 

X 
 

A d diti o nal e xa ms perf or me d at i n vesti gat or discreti o n. See Secti o n 8. 3. 2 f or a d diti o nal 
details . 
Res pirat or y rate
X
 

X 
 

X
S u pi ne B P a n d p ulse 
rate
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Tri plicate s u pi ne bl o o d press ure a n d p ulse rate at all ti mes. See Secti o n 8. 3. 3 f or 
a d diti o nal details.
1 2 -Lea d E C G
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Tri plicate meas ure me nt s at all ti me p oi nts. See Secti o n 8. 3. 4 f or a d diti o nal details.
C o nti n u o us car diac 
tele metr y
X
 
 
 
 
 

X
See Secti o n 8. 3. 4. 1 f or a d diti o nal details. 
Sta n dar dize d
meal s/s nac k
 
 
 

X

X
See Secti o n 5. 3. 2 .
Bl o o d s a m pli n g f or: 
Retai ne d Researc h 
Sa m ple f or Bi o mar kers
(P re p B2 . 5)
X
X
T o be c ollecte d as o utli ne d i n Secti o n 8. 7. 4 .
P F - 0 7 8 5 3 5 7 8 plas ma 
P K
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
See Secti o n 8. 5 for a d diti o nal i nf or mati o n. 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. I N T R O D U C TI O N
P F -0 7 8 5 3 5 7 8 is a first -i n-class, orall y a d mi nistere d, s mall m olec ule c o vale nt m o difier of 
P N P L A 3 t hat is c urre ntl y bei n g de vel o pe d f or t he treat me nt of N A S H wit h li ver fi br osis i n 
patie nts w h o are carriers of t he P N P L A 3 -1 4 8 M allele.
2. 1. St u d y R ati o n ale 
T his st u d y  will be t he first ti me P F -0 7 8 5 3 5 7 8 is a d mi nistere d t o h u ma ns. T he p ur p ose of t he 
st u d y is t o e val uate t he safety, t olera bilit y , a n d plas ma P K of P F- 0 7 8 5 3 5 7 8 f oll o wi n g 
a d mi nistrati o n of escalati n g, si n gle oral d oses t o healt h y a d ult partici pa nts.
2. 2. B ac k gr o u n d 
2. 2. 1. P N P L A 3 a n d N A F L D/ N A S H
N A F L D , a n d t he m ore seri o us f or m of t he disease N A S H, is t he m ost pre vale nt li ver disease 
i n Wester n c o u ntries.[1 ] It is esti mate d t hat 2 5 % of a d ults i n de vel o pe d c o u ntries ha ve 
N A F L D , a n d u p t o 6 % ha ve N A S H .[2 ] N A F L D is c haracterize d b y e xcessi ve acc u m ulati o n 
of he patic li pi d (steat osis). A s u bset of patie nts wit h N A F L D pr o gress t o N A S H, w hic h is 
defi ne d as t he hist ol o gical prese nce of he patic steat osis, i nfla m mati o n , a n d he pat ocell ular 
i nj ur y ( he pat oc yte ball o o ni n g).[3 ] S o me patie nts wit h N A S H de vel o p pr o gressi ve he patic 
fi br osis, a n d if left u ntreate d , N A S H ca n pr o gress t o life -t hreate ni n g c o n diti o ns s uc h as 
cirr h osis a n d H C C. [4 ]
O ne of t he str o n gest ge netic ris k fact ors i de ntifie d f or N A F L D is t he rs 7 3 8 4 0 9 varia nt i n t he 
P N P L A 3 ge ne w hic h e nc o des a n is ole uci ne t o met hi o ni ne s u bstit uti o n at a mi n o aci d p ositi o n 
1 4 8 of t he P N P L A 3 pr otei n ( P N P LA 3 -1 4 8 M ).[5 ] T he P N P L A 3 -1 4 8 M allele is c o m m o n a n d 
f o u n d i n 2 3 % of t he t otal p o p ulati o n wit h hi g her fre q ue ncies i n t he Lati n o p o p ulati o n ( 4 2 %) 
a n d l o wer fre q ue ncies a m o n g Africa n/ Africa n A merica n p o p ulati o ns ( 1 4 %) .[6 , 7 ] Carriers of 
the P N P L A 3 -1 4 8 M allele als o ha ve a hi g her ris k of N A S H, cirr h osis, he patic 
dec o m pe nsati o n, H C C , a n d li ver-relate d a n d all-ca use m ortalit y .[8- 1 2 ]
P N P L A 3 is a tri gl yceri de li pase f o u n d o n li pi d dr o plets. C o m pare d t o wil dt y pe P N P L A 3 
( P N P LA 3 -W T), t he P N P L A 3 -1 4 8 M pr otei n has re d uce d catal yt ic acti vit y a n d acc u m ulates 
o n he patic li pi d dr o plets .[1 3 ] T he acc u m ulati o n of P N P LA 3 -1 4 8 M pr otei n o n he patic li pi d 
dr o plets is re q uire d i n a “ gai n -of -pat h o ge nic -f u ncti o n” ma n ner t o pr o m ote N A F L D a n d 
N A S H i n mice, a n d re d ucti o ns i n P N P L A 3 -1 4 8 M pr otei n le vels i n mice usi n g A S Os, 
s h R N As, or P R O T A C tec h n ol o g y re d uces he patic steat osis, i nfla m mati o n , a n d fi br osis.[1 4 , 
1 5 ] P F - 0 7 8 5 3 5 7 8 is a p ote nt, orally- bi oa vaila ble, s mall -m olec ule i n hi bit or of P N P L A 3 t hat 
has bee n de m o nstrate d i n n o ncli nical m o dels t o de gra de P N P L A 3 - 1 4 8 M pr otei n a n d re d uce 
he patic tri gl yceri des a n d is p ost ulate d t o decrease steat osis i n P N P L A 3 -1 4 8 M carriers wit h 
N A S H .
2. 2. 2. N o ncli nic al P h ar m ac ol o g y
P F -0 7 8 5 3 5 7 8 is a n i n hi bit or of P N P L A 3 t hat irre versi bl y c o vale ntly m o difies a n d de gra des 
t he P N P LA 3 pr otei n.
 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
 
 
 
 
 
In mice 
e x pressi n g h u ma n P N P L A 3 -1 4 8 M fr o m a B A C -T G, a d mi nistrati o n of P F - 0 7 8 5 3 5 7 8 d ose-
de pe n de ntl y re d uce d P N P L A 3 - 1 48 M pr otei n i n li ver tiss ue. P F -0 7 8 5 3 5 7 8 a d mi nistrati o n als o 
re d uce d P N P L A 3-1 4 8 M pr otei n acc u m ulati o n a n d steat osis i n B A C - T G mice t hat were fe d a 
hi g h s ucr ose diet t o pr o m ote P N P L A 3 -1 4 8 M pr otei n acc u m ulati o n a n d steat osis. A d diti o nal 
details are i ncl u de d i n t he I B.
2. 2. 3. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
T he oral bi oa vaila bilit y  of P F - 0 7 8 5 3 5 7 8 was varia ble acr oss n o ncli nical s pecies ra n gi n g 
fr o m 
 at t he hi g h er d ose i n mice. T he C L p i n rats was  
, b ut 
 i n mice, d o gs, a n d m o n ke ys, wit h  
 Vss a n d a t ½ of a p pr o xi matel y   
 
or s h orter. F oll o wi n g I V a d mi nistrati o n of P F -0 7 8 5 3 5 7 8 i n rats, d o gs, a n d m o n ke ys, t he 
perce nt of P F - 0 7 8 5 3 5 7 8 d ose rec o vere d u nc ha n ge d i n uri ne was 
. S yste mic 
e x p os ure of P F -0 7 8 5 3 5 7 8 i n re peat oral d ose t o xic ol o g y st u dies i ncrease d wit h i ncreasi n g 
d ose i n rats a n d d o gs, h o we ver, e x p os ure decrease d o ver t he d urati o n of d osi n g i n 
c o m paris o n t o Da y 1 at t he mi d a n d hi g h d ose le vels i n rat a n d at all d oses i n d o g. T here was 
n o e vi de nce of acc u m ulati o n i n eit her s pecies. S y ste mic e x p os ure of P F -0 7 8 5 3 5 7 8 was 
hi g her i n fe male rats t ha n i n male rats at all d ose le vels, wit h n o se x -relate d differe nces i n 
e x p os ure i n d o gs. I n vitr o, P F- 0 7 8 5 3 5 7 8 was n ot a s u bstrate f or 
 
. 
P F - 0 7 8 5 3 5 7 8 was si milarl y  hi g hly b o u n d t o rat, d o g, a n d h u ma n plas ma pr otei ns a n d 
prefere ntiall y distri b ute d i nt o plas ma vers us bl o o d acr oss t he s pecies. P F -0 7 8 5 3 5 7 8 als o 
distri b ute d i nt o t he brai n i n rat after oral d osi n g. 
I n vitr o meta b olite pr ofili n g s u g gests t hat t he pri mar y cleara nce mec ha nis m f or P F-0 7 8 5 3 5 7 8 
was 
 
wit h n o u ni q ue h u ma n meta b olites o bser ve d. 
was res p o nsi ble f or a maj orit y  of t he 
meta b olis m of P F -0 7 8 5 3 5 7 8 wit h mi n or c o ntri b uti o ns attri b ute d t o 
 
.
Base d o n F D A a n d E M A g ui da nces,[ 1 6 , 1 7 ] P F -0 7 8 5 3 5 7 8 has a l o w ris k of eliciti n g D DI as 
a res ult of i n hi biti o n of C Y P or U G T e nz y mes b ut has t he p ote ntial t o elicit 
 
 at t he pr ojecte d efficaci o us h u ma n d ose a n d t he d ose ra n ge pla n ne d f or 
t he c urre nt cli nical st u d y. P F - 0 7 8 5 3 5 7 8 m a y  per petrate D DI wit h 
 
. In a d diti o n, t here is a p ote ntial f or D DIs w hic h c o ul d occ ur wit h P F -0 7 8 5 3 5 7 8 as 
a victi m if c o-a d mi nistere d wit h m o derate a n d/ or p ote nt cli nical i n hi bit ors or i n d uc ers of 
.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A d diti o nal details are i ncl u de d i n t he I B.
2. 2. 4.
 
 
 
 
 
2. 2. 5. N o ncli nic al S afet y
P F - 0 7 8 5 3 5 7 8 was e val uate d i n G L P -c o m plia nt re peat -d ose ge neral t o xicit y  st u dies u p t o 
2 wee ks i n d urati o n i n rats a n d d o gs, i n vitr o a n d i n vi v o ge netic t o xicit y  st u dies, a n d safet y 
p har mac ol o g y  st u dies i n rats f or assess me nt of ne ur of u ncti o nal a n d p ul m o nar y effects or 
d o gs f or car di o vasc ular effects. 
P F - 0 7 8 5 3 5 7 8 was n ot m uta ge nic, a ne u ge nic or clast o ge nic. I n t he si n gle -d ose safet y 
p har mac ol o g y  st u dies,
 
 
 effects were n ote d i n rats, a n d a N O E L was esta blis he d i n 
t hese st u dies.
I n t he 2-wee k G L P re peat -d ose t o xicit y  st u dies,
 
 
 
. T he N O A E Ls i n t he G L P t o xicit y st u dies 
were esta blis he d at 1 0 0 0 m g/ k g/ da y  i n rats a n d d o gs. I n rats, t he N O A E L c orres p o n de d t o a 
t otal Cma x of 
 
. 
I n s u m mar y, t he n o ncli nical safet y pr ofile of P F -0 7 8 5 3 5 7 8 has bee n a de q uatel y  c haracterize d 
a n d s u p p orts pr o gressi o n i nt o cli nical trials of u p t o 1 4 da y s i n d urati o n. A d diti o nal details of 
t he n o ncli nical safet y pr o gra m are pr o vi de d i n t he I B. 
2. 3. Be nefit/ Ris k Assess me nt
St u d y  C 5 1 6 1 0 0 1 is t he first ti me t hat P F- 0 7 85 3 5 7 8 will be a d mi nistere d t o h u ma ns a n d is
desi g ne d pri maril y t o ge nerate safet y, t olera bilit y , a n d P K data f or f urt her cli nical
de vel o p me nt. P F -0 7 8 5 3 5 7 8 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 pr o vi de t he basis f or f urt her cli nical de vel o p me nt
of P F - 0 7 8 5 3 5 7 8 as a first-i n-class t hera p y f or treat me nt of N A S H wit h li ver fi br osis i n 
patie nts w h o are carriers of t he P N P LA 3 -1 4 8 M allele. As of t he date of t his pr ot oc ol, n o 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
s pecific h u ma n ris ks ha ve bee n i de ntifie d; p ost ulate d ris ks base d o n n o ncli nical st u dies are 
s u m marize d i n Secti o n 2. 2. 5 . T he cli nical i m pact of t hese p ote ntial ris ks will be mi ni mize d 
wit h preca uti o nar y  se nti nel d osi n g a n d t hr o u g h t he pr o p ose d ca uti o us d ose-escalati o n pr ocess 
w herei n hi g her d oses of P F -0 7 8 5 3 5 7 8 will be a d mi nistere d o nl y  after l o wer d oses ha ve bee n 
f o u n d t o be well t olerate d wit h a n acce pta ble safet y pr ofile. I n a d diti o n, t his st u d y will 
e m pl o y st o p pi n g r ules f or d ose escalati o n (Secti o n 6. 6. 1 ) a n d i ncl u des sta n dar d, i nte nsi ve, 
i n patie nt m o nit ori n g of t he partici pa nts f oll o wi n g d ose a d mi nistrati o n as o utli ne d i n t he S o A .
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A E s of P F -0 7 8 5 3 5 7 8 ma y  be f o u n d i n t he I B, w hic h is t he S R S D f or t his st u d y. 
Refer t o t he St u d y  Inter ve nti o n(s) ta ble i n Secti o n 6. 1 f or a c o m plete descri pti o n of S R S Ds. 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 5 3 5 7 8 
P ote ntial off -tar get a d verse effects
P F -0 7 8 5 3 5 7 8 is a 
, 
 
. Off-tar get i nteracti o ns 
i de ntifie d
 
 
 ma y i ncl u de 
 
at hi g h c o nce ntrati o ns.  
D uri n g t he st u d y, partici pa nts will be i n a cl osel y m o nit ore d e n vir o n me nt 
w hile i n t he C R U. 
H u ma n e x p os ures wit hi n t he pla n ne d d ose ra n ge are pr ojecte d t o all be 
bel o w  c o nce ntrati o ns
 
Preca uti o nar y se nti nel d osi n g will be use d i n t his st u d y.
Ne ur ol o gic e xa ms vital si g ns, E C G c he mistries, a n d fasti n g li pi ds will be 
i nc or p orate d as part of safet y m o nit ori n g.
S m aller d ose escalati o n ste ps ma y be i m ple me nte d if cli nicall y si g nifica n t 
safet y para meter c ha n ges are o bser ve d.
Dr u g -dr u g i nteracti o ns res ulti n g i n 
e x p os ure c ha n ges of bac k gr o u n d 
c o nc o mita nt me dicati o ns
At t he d ose ra n ge pla n ne d f or t he 
c urre nt st u d y, P F -0 7 8 5 3 5 7 8 has 
t he p ote ntial t o elicit 
 
.
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 will be pr o hi bite d wit hi n 7 da ys 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 t hr o u g h t he last P K 
c ollecti o n.
Dr u g -dr u g i nteracti o ns res ulti n g i n 
P F -0 7 8 5 3 5 7 8 e x p os ure c ha n ges
 was res p o nsi ble f or a 
maj orit y of t he meta b olis m of 
P F -0 7 8 5 3 5 7 8 i n vitr o.
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 t hat are m o derate or str o n g  
 i n d ucers or i n hi bit ors are 
pr o hi bite d w it 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 t hr o u g h t he last P K c ollecti o n.
Effects o n li pi ds
 
were see n i n 1 4-da y G L P 
t o xic ol o g y st u dies wit h 
P F -0 7 8 5 3 5 7 8 i n rats a n d d o gs .
Fasti n g li pi d pa nels will be i ncl u de d as part of t he cli nical safet y la bs.
Effects o n o varies a n d a dre nals
I n 1 4-d a y  G L P t o xic ol o g y st u dies 
wit h P F -0 7 8 5 3 5 7 8 ,
 
 was 
see n i n fe male rats, a n d mil d-
m o derate vac u olati o n of a dre nal 
W O C B P will be e xcl u de d fr o m t he st u d y .
Vital si g ns a n d electr ol ytes i n sta n dar d cli nical safet y la bs will be
perf or me d seriall y t o m o nit or f or si g ns of a dre nal i ns ufficie nc y.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 5 3 5 7 8 
gla n ds was see n i n fe male a n d 
male rats.
Effects o n t he li ver
N o n -a d verse i ncreases i n li ver 
wei g ht a n d he pat oc yte 
h y pertr o p h y were see n i n rats, 
a n d i ncrease d A L T i n fe male 
d o gs wit h P F -0 7 8 5 3 5 7 8 i n 1 4 -da y 
G L P t o xic ol o g y st u dies .
Serial li ver f u ncti o n tests will be meas ure d as part of sta n dar d cli nical
safet y la bs.
Effects o n p ul m o nar y f u ncti o n
 
 
were see n i n rats wit h 
P F -0 7 8 5 3 5 7 8 in si n gle-d ose 
safet y p har mac ol o g y st u dies.
Res pirat or y rate will be assesse d seriall y as part of safet y m o nit ori n g.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 6
2. 3. 2. Be nefit Assess me nt
T he partici pa nts i n t his st u d y  are n ot e x pecte d t o o btai n a n y s pecific be nefit be yo n d
c o ntri b uti n g t o t he pr ocess of de vel o pi n g ne w t hera pies i n a n area of u n met nee d. T he y will
recei ve cl ose m o nit ori n g of t heir safet y via st u d y pr oce d ures u n derta ke n (e g, P Es , 1 2-lea d 
E C Gs, vital si g ns) w hic h will occ ur as o utli ne d i n t his pr ot oc ol.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
Base d o n t he t otalit y  of a vaila ble n o ncli nical data a n d 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 o verall be nefit/ris k pr ofile s u p p orts cli nical testi n g of 
P F -0 7 8 5 3 5 7 8 i n t his st u d y  as part of t he cli nical de vel o p me nt f or t he treat me nt of N A S H 
wit h li ver fi br osis i n patie nts w h o are carriers of t he P N P L A 3 -1 4 8 M allele .
3. O B J E C TI V E S A N D E N D P O I N T S
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y: 

T o e val uate t he safet y a n d t olera bilit y of si n gle 
asce n di n g d oses of P F - 0 7 8 5 3 5 7 8 a d mi nistere d 
orall y t o healt h y a d ult partici pa nts.

Assess me nt of A Es, cli nical safet y la b orat or y tests, 
vital si g ns, c o nti n u o us car diac m o nit ori n g, 1 2 -lea d 
E C Gs, P Es , a n d ne ur ol o gical e xa mi nati o ns.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he P K of P F -0 7 8 5 3 5 7 8 f oll o wi n g 
si n gle d oses of P F- 0 7 8 5 3 5 7 8 a d mi nistere d orall y t o 
healt h y a d ult partici pa nts.

P K para meters deri ve d fr o m plas ma P F -0 7 8 5 3 5 7 8 
c o nce ntrati o ns: C ma x, Tma x , A U Clast, a n d if data per mit , 
A U C i nf a n d t ½ .
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y: 

T o e val uate a d diti o nal P K para meters of 
P F -0 7 8 5 3 5 7 8 f oll o wi n g si n gle d oses of 
P F - 0 7 8 5 3 5 7 8 a d mi nistere d orall y t o healt h y a d ult 
partici pa nts.

A d diti o nal P K para meters deri ve d fr o m plas ma 
P F -0 7 8 5 3 5 7 8 c o nce ntrati o ns: C ma x( d n), A U C last( d n), 
a n d if data per mit, A U C i nf( d n), C L/ F, a n d V z/ F.

T o e val uate t he effect of f o o d o n t he P K of 
P F -0 7 8 5 3 5 7 8 f oll o wi n g si n gle d oses of 
P F - 0 7 8 5 3 5 7 8 a d mi nistere d orall y t o healt h y a d ult 
partici pa nts (if c o n d ucte d).

P K para meters deri ve d fr o m plas ma P F -0 7 8 5 3 5 7 8 
c o nce ntrati o ns after a hi g h -fat/ hi g h-cal orie meal : 
C ma x, Tma x , A U Clast, a n d if data per mit, A U C i nf a n d t ½ .

T o e val uate t he P K of P F -0 7 8 5 3 5 7 8 f oll o wi n g 
si n gle oral d oses of a n I D S oral s ol uti o n of 
P F - 0 7 8 5 3 5 7 8 a d mi nistere d orall y t o healt h y a d ult 
partici pa nts (if c o n d ucte d).

P K para meters deri ve d fr o m plas ma P F -0 7 8 5 3 5 7 8 
c o nce ntrati o ns after I D S oral s ol uti o n d osi n g : Cma x, 
T ma x , A U Clast, a n d if data per mit, A U C i nf a n d t ½ .
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his st u d y  is a ra n d o mize d, i n vesti gat or- a n d partici pa nt -bli n d, s p o ns or -o pe n, 
place b o -c o ntr olle d, FI H, si n gle asce n di n g d ose, 4- peri o d, cr oss o ver, i nterlea vi n g desi g n 
st u d y of P F-0 7 8 5 3 5 7 8 orall y  a d mi nistere d t o healt h y a d ult partici pa nts. A p pr o xi matel y 
2 4 healt h y  a d ult partici pa nts ( u p t o 3 c o h orts of a p pr o xi matel y 8 partici pa nts eac h) will be 
e nr olle d i n t his st u d y. T he o pti o nal t hir d c o h ort will o nl y be use d if t he o bjecti ves of t he 
st u d y are n ot f ulfille d i n C o h ort 1 a n d C o h ort 2. Eac h partici pa nt is pla n ne d t o u n der g o 
4 treat me nt peri o ds recei vi n g u p t o 4 d oses of P F -0 7 8 5 3 5 7 8 a n d u p t o 2 d oses of place b o. I n 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
eac h peri o d, partici pa nts will be ra n d o mize d t o eit her P F- 0 7 8 5 3 5 7 8 or place b o i n a rati o of 
6 : 2. A dia gra m of t he st u d y  desi g n is s h o w n i n Fi g ure 1 .
Preca uti o nar y  se nti nel d osi n g will be use d i n a n y peri o d e val uati n g escalati n g d oses of 
P F - 0 7 8 5 3 5 7 8. T w o partici pa nts ( 1 recei vi n g P F-0 7 8 5 3 5 7 8 a n d 1 recei vi n g place b o) wit hi n a 
peri o d will be d ose d i nitiall y bef ore t he re mai ni n g partici pa nts of t hat peri o d are d ose d. 
Safet y  a n d t olera bilit y data t hr o u g h at least 2 4 h o urs p ost-d ose f or t he se nti nel partici pa nts 
will be re vie we d pri or t o d osi n g t he re mai ni n g parti ci pa nts of t hat peri o d. Se nti nel d osi n g 
ma y  be o mitte d w he n re peati n g a d ose le vel or a d mi nisteri n g a l o wer d ose le vel t ha n 
pre vi o usl y  e val uate d.
Scree ni n g acti vities will be c o m plete d o ver t he 2 8 da y s pri or t o ra n d o mizati o n i n Peri o d 1. I n 
eac h peri o d, partici pa nts will be a d mitte d t o t he C R U o n Da y  -1 a n d will re mai n i n t he C R U 
t hr o u g h at least t he 7 2-h o ur assess me nts o n Da y  4. Partici pa nts ma y  re mai n i n t he C R U after 
c o m pleti o n of Da y 4 acti vities at t he discreti o n of t he i n vesti gat or or if safet y, t olera bilit y, or 
P K data dictate t he nee d t o pr ol o n g c o nfi ne me nt i n t he C R U. Partici pa nts will recei ve a 
si n gle oral d ose of P F-0 7 8 5 3 5 7 8 or place b o o n Da y  1 of eac h peri o d. D ose le vels will be 
escalate d t o brac ket t he e x pecte d cli nical d ose ra n ge, b ut t he pr oje cte d e x p os ures will n ot 
e xcee d t he pre defi ne d h u ma n e x p os ure li mits. Wit hi n a n i n di vi d ual partici pa nt, t here will be 
a was h o ut i nter val of at least 1 0 da y s bet wee n d oses. T he t otal d urati o n of partici pati o n fr o m 
t he scree ni n g visit t o t he tele p h o ne f oll o w-u p c o ntact will be a p pr o xi matel y 1 7 wee ks f or 
eac h partici pa nt . Partici pa nts will ret ur n f or a n o n-site f oll o w-u p visit 7 - 1 0 da y s after t he 
fi nal d ose of st u d y i nter ve nti o n. T he f oll o w -u p c o ntact ma y  occ ur via tele p h o ne c o ntact a n d 
m ust occ ur 2 8 -3 5 da y s after a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n. 
D osi n g will occ ur i n t he faste d state f or all peri o ds, e xce pt if a n o pti o nal e x pl orat or y 
assess me nt of t he effect of f o o d o n P F - 0 7 8 5 3 5 7 8 P K is c o n d ucte d . If t he f o o d effect is
e val uate d, it is a ntici pate d t hat st u d y  i nter ve nti o n will be a d mi nistere d i n t he fe d state i n t he
last peri o d of C o h ort 2 or C o h ort 3 at a d ose le vel t hat was pre vi o usly a d mi nistere d faste d
wit hi n t he sa me c o h ort. H o we ver, st u d y  i nter ve nti o n ma y be a d mi nistere d i n t he fe d state
d uri n g a n y of t he st u d y peri o ds/c o h orts if t h o u g ht necessar y t o ac hie ve st u d y o bjecti ves. T he
act ual d ose le vel will be selecte d base d o n e mer gi n g safet y, t olera bilit y, a n d P K data b ut will
be e x pecte d t o ac hie ve a p pr o xi mate pr ojecte d t hera pe utic e x p os ures ( Secti o n 4. 3. 2 ).
If e val uate d, t he I D S oral s ol uti o n of P F -0 7 8 5 3 5 7 8 is a ntici pate d t o be assesse d i n t he last 
peri o d of C o h ort 2 or C o h ort 3 at a d ose le vel t hat was pre vi o usl y a d mi nistere d as a 
s us pe nsi o n wit hi n t he sa me c o h ort . H o we ver, t he I D S oral s ol uti o n ma y  be a d mi nistere d 
d uri n g a n y of t he st u d y peri o ds/c o h orts if t h o u g ht necessar y t o ac hie ve st u d y o bjecti ves.
If a partici pa nt dr o ps o ut bef ore c o m pleti n g all st u d y peri o ds wit hi n a c o h ort or wit h dra ws 
f or a reas o n u nrelate d t o t he safety of t he st u d y i nter ve nti o n, t he partici pa nt ma y be re place d 
at t he discreti o n of t he i n vesti gat or a n d s p o ns or. T he re place me nt par tici pa nt(s) ma y or ma y 
n ot be re q uire d t o c o m plete all peri o ds of t he c o h ort i n w hic h t he y  are partici pati n g at t he 
discreti o n of t he i n vesti gat or a n d s p o ns or.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T he p ur p ose of t his st u d y is t o e val uate t he safet y, t olera bilit y, a n d P K of orall y a d mi nistere d 
d oses of P F -0 7 8 5 3 5 7 8 a n d place b o i n healt h y  a d ult males a n d fe male partici pa nts of 
n o n-c hil d beari n g p ote ntial. Fe male partici pa nts will be c o nfir me d n ot t o be of c hil d beari n g 
p ote ntial
 
, a n d re pr o d ucti ve t o xicit y st u dies wit h 
P F -0 7 8 5 3 5 7 8 ha ve n ot bee n c o n d ucte d. I n male partici pa nts, a p pr o priate meas ures are 
e x pecte d t o be f oll o we d t o mi ni mize p ote ntial tra nsfer of P F -0 7 8 5 3 5 7 8 via se me n t o part ners 
(see A p pe n di x 4 ).
Beca use t his is t he first ti me P F-0 7 8 5 3 5 7 8 will be a d mi nistere d t o h u ma ns, a n escalati n g 
si n gle, oral d ose, cr oss o ver i nterlea vi ng desi g n is pla n ne d wit h caref ul assess me nt a n d 
o n g oi n g re vie w of safet y,  t olera bilit y, a n d P K data of P F-0 7 8 5 3 5 7 8. I n eac h peri o d, 
6 partici pa nts are pla n ne d t o recei ve P F- 0 7 8 5 3 5 7 8, a n d 2 partici pa nts are pla n ne d t o recei ve 
place b o. Se nti nel d osi n g will b e utilize d t o e ns ure t hat safet y a n d t olera bilit y data i n a s u bset 
of 2 partici pa nts at eac h d ose le vel s u p p orts t he testi n g of a d diti o nal partici pa nts . T h e 
cr oss o ver desi g n per mits b ot h wit hi n - a n d bet wee n -partici pa nts assess me nts of safet y, 
t olera bilit y, a n d P K at m ulti ple d ose le vels a n d place b o.
T he hi g hest a ntici pate d C ma x a n d A U C 2 4 of P F -0 7 8 5 3 5 7 8 will n ot e xcee d t he pre -defi ne d 
h u ma n e x p os ure st o p pi n g li mits. F urt her m ore, t o per mit a n u n biase d assess me nt of safet y, 
t he a d mi nistrati o n of b ot h P F- 0 7 8 5 3 57 8 a n d place b o i n eac h peri o d will be bli n d t o b ot h site 
staff (e xce pt t h ose i n v ol ve d i n pre parati o n of d oses) as well as t he partici pa nts. T o per mit 
real-ti me re vie w of t he safet y, t olera bilit y, a n d P K data, a li mite d n u m ber of s p o ns or st u d y 
tea m me m bers will be u n bli n de d.
A n i nterlea vi n g desi g n will be e m pl o y e d i n t his st u d y t o s prea d P F-0 7 8 5 3 5 7 8 d ose le vels
acr oss a wi de ra n ge wit hi n a n i n di vi d ual partici pa nt a n d t o re d uce t he ris k of carr y o ver 
effects o n P K a n d t he a ntici pate d d y na mics of P N P L A 3 le vels ret ur n t o baseli ne acr oss t he 
pla n ne d d ose /e x p os ure ra n ge. T he d urati o n of ti me bet wee n t he i nterlea vi n g d ose escalati o n 
peri o ds i n C o h ort 1 a n d C o h ort 2 will be deter mi ne d b y  t he ti me re q uire d f or a nal ys is a n d
re vie w of t he safet y, t olera bilit y, a n d P K data fr o m eac h d osi n g peri o d bef ore ma ki n g a 
decisi o n o n t he s u bse q ue nt P F - 0 7 8 5 3 5 7 8 d ose le vel t o be e val uate d. T heref ore, t he d urati o n 
of ti me bet wee n d oses i n a n i n di vi d ual partici pa nt will be ≥1 0 da y s beca use a t hi g h d oses of 
P F -0 7 8 5 3 5 7 8 , P N P LA 3 le vels are pre dicte d t o ret ur n t o baseli ne i n ≤7 da ys.
Base d o n t he pre dicte d t½ of P F - 0 7 8 5 3 5 7 8, plas ma c o nce ntrati o ns of P F -0 7 8 5 3 5 7 8 are 
e x pecte d t o be bel o w t he li mit of detecti o n i n a p pr o xi matel y 3 d a y s, t h us P K sa m ples are 
pla n ne d t o be c ollecte d o ver 7 2 h o urs p ost -d ose. H o we ver, sa m pli n g ti mes, d urati o n of 
sa m pli n g, a n d/ or t he le n gt h of t he i nter val bet wee n d oses ma y  be mo difie d a n d/ or e xte n de d 
base d o n e mer gi n g P K. T he pla n ne d d oses i n t he d ose escalati o n seq ue nce ( Ta ble 3 ) ma y be 
m o difie d or re peate d, as g ui de d b y e mer gi n g safet y, t olera bilit y, a n d P K data b ut will f oll o w 
t he d ose-escalati o n r ules defi ne d i n Secti o n 6. 6. 1 .
Ne ur ol o gical e xa mi nati o ns will be c o n d ucte d
 
. Ne ur ol o gic si g ns 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
will be m o nit ore d cl osel y pre - a n d p ost-d ose, a n d partici pa nts will re mai n i n a cl osel y 
m o nit ore d e n vir o n me nt f or 7 2 h o urs p ost - d ose, w hic h is dee me d s ufficie nt base d o n t he 
pre dicte d effecti ve t ½ of P F - 0 7 8 5 3 5 7 8.
Res pirat or y  rate will be assesse d
 
 
.
A fasti n g li pi d pa nel, c o nsisti n g of t otal c h olester ol, tri gl yceri des, H D L, a n d direct L D L, will 
be m o nit ore d wit h cli nical safety la b tests
 
F o o d m a y  i ncrease P F -0 7 8 5 3 5 7 8 e x p os ures, t heref ore a n e x pl orat or y assess me nt of t he effect 
of f o o d o n P F -0 7 8 5 3 5 7 8 P K ma y  be c o n d ucte d t o c o nfir m i n silic o pre dicti o ns.
 
 
 
 
 
 
 
 
 
P G x bl o o d sa m ples will be c ollecte d f or retr os pecti ve ge n ot y pi n g of P N P L A 3 p ol y m or p his m 
(rs 7 3 8 4 0 9) i n eac h partici pa nt. T his data m a y e na ble assess me nts of differe ntial safety , 
t olera bilit y, a n d P K b y  ge n ot yp e a n d m a y i nf or m t he desi g n of s u bse q ue nt cli nical st u dies 
wit h P F - 0 7 8 5 3 5 7 8. 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.
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
St u dies t o e val uate t he de vel o p me ntal t o xicit y  of P F -0 7 8 5 3 5 7 8 ha ve n ot bee n c o n d ucte d . 
T heref ore, t he use of a hi g hl y effecti ve met h o d of c o ntrace pti o n is re q uire d f or male st u dy 
partici pa nts a n d is rec o m me n de d f or part ne rs of male st u d y partici pa nts w h o are W O C B P
(see A p pe n di x 4 ).
4. 3. J ustific ati o n f or D ose
T he pr o p ose d d ose le vels of P F - 0 7 8 5 3 5 7 8 were deri ve d base d o n c u m ulati ve n o ncli nical 
data, i ncl u di n g i n vitr o, i n vi v o, P K a n d P D data, a n d t he c o m plete d n o ncli nical t o xicit y 
st u dies. D ose le vels ha ve bee n selecte d t o brac ket t he e x pecte d cli nical d ose a n d e x p os ure 
ra n ge, w hile c o nsi deri n g u ncertai nty i n t he pr ojecte d cli nicall y efficaci o us d ose. D ose le vels 
be y o n d t he st arti n g d ose (i n Peri o d 1 of C o h ort 1) ma y  be m o difie d base d o n e mer gi n g 
h u ma n safet y, t olera bilit y, a n d P K data i n t he c urre nt st u d y.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
4. 3. 1. H u m a n P K P re dicti o ns
P F -0 7 8 5 3 5 7 8 is pre dicte d t o ha ve
 
 
. 
4. 3. 2. Pre dicte d Effic aci o us C o nce ntr ati o n a n d H u m a n D ose
T he h u ma n efficaci o us d ose of P F -0 7 8 5 3 5 7 8 was pr ojecte d t o be 
 
 pr otei n l o weri n g as a n 
 
. T he tar gete d 
 
 
[5 ] a n d n o ncli nical data w here a 
% re d ucti o n i n P N P L A 3 -1 4 8 M pr otei n le vels res ulte d i n a 
% decrease i n he patic 
tri glyceri de c o nte nt i n mice e x pressi n g t he varia nt pr otei n via a tra ns ge ne. T he d ose 
pr ojecti o n c o m bi ne d pre dicte d h u ma n P K para meters i n a o ne-c o m part me nt P K m o del a n d a 
d y na mic P D m o del t hat
 
 as deri ve d fr o m i n vitr o st u dies usi n g h u ma n 
he pat oc y tes 
 ris k allele. 
T he pre dicte d efficaci o us d ose of
 
. 
4. 3. 3. H u m a n E x p os ure St o p pi n g Li mits
T he N O A E L d ose le vels i n t he pi v otal 2-wee k G L P t o xicit y  st u dies were 1 0 0 0 m g/ k g/ da y  
( 1 00 0 m g/ k g Q D) i n rats a n d 1 0 0 0 m g/ k g/ da y  ( 5 0 0 m g/ k g BI D) i n d o gs , w hic h were t he 
hi g hest d oses teste d i n t h ose res pecti ve st u dies. T he o bser ve d N O A E L e x p os ures i n d o gs
were l o wer c o m pare d t o N O A E L e x p os ures i n rats. At t he N O A E L i n d o gs, t he t otal C ma x
a n d A U C 2 4 were 
 n g/ m L a n d  
 n g• h/ m L, 
. T heref ore, t he h u ma n 
e x p os ure st o p pi n g li mits f or P F -0 7 8 5 3 5 7 8 are :
4. 3. 4. R ati o n ale f or D ose Selecti o n
T he safet y, t olera bilit y , a n d plas ma P K of P F - 0 7 8 5 3 5 7 8 after a d mi nistrati o n of si n gle 
escalati n g oral d oses acr oss a wi de d ose/e x p os ure ra n ge will be e val uate d i n t his st u d y . 
D osi n g will occ ur i n t he faste d state, e xce pt i n peri o ds i n w hic h d osi n g ma y  occ ur i n t he fe d 
state t o per mit e x pl orat or y assess me nt of t he effect of f o o d o n P F -0 7 8 5 3 5 7 8 P K . T he d oses 
prese nte d i n Ta ble 3 are pr ojecte d base d o n n o ncli nical data a n d ma y  be m o difie d base d o n 
e mer gi n g o bser ve d h u ma n safet y, t olera bilit y, a n d P K data ge nerate d d uri n g t his st u d y . The 
i nitial ra n ge of pla n ne d d oses i n t his st u d y were esta blis he d usi n g t o xic o ki netic data,
p re dicte d h u ma n P K para meter esti mates, pr ojecte d P N P L A 3 re d ucti o n, a n d pr ojecte d 
efficaci o us c o nce ntrati o ns .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 3.
Pre dicte d H u m a n E x p os ures, Pr ojecte d Li ver P N P L A 3 Re d ucti o n, a n d 
S afet y M ar gi ns at Pr o p ose d Si n gle D oses of P F - 0 7 8 5 3 5 7 8
D ose
( mg)
1
3
1 0
3 0
7 5
1 5 0
3 0 0
A P F -0 7 8 5 3 5 7 8 starti n g d ose le vel of 1 m g is pla n ne d. T h is starti n g d ose le vel was i nf or me d 
b y
 
a n d was selecte d t o ac hie ve pr ojecte d mi ni mal 
P D acti vit y. At a si n gle d ose of 1 m g , P F -0 7 8 5 3 5 7 8 e x p os ures are pr ojecte d t o be well bel o w 
e x p os ures ass ociated wit h efficac y a n d t he h u ma n e x p os ure li mits. 
 
 are pr ojecte d t o be re d uce d b y 
a p pr o xi matel y 
, res pecti vely, at C ma x , s u g gesti n g mi ni mal P D acti vit y. T he 
p re dicte d C ma x a n d C a v are:

, bel o w t he h u ma n e x p os ure li mits 
defi ne d f or P F-0 7 8 5 3 5 7 8 d ose escalati o n i n Secti o n 4. 3. 3 . 
T he d ose ra n ge t o be st u die d was selecte d t o acc o u nt f or u ncertai nties i n t he pr ojecte d C eff
a n d t he pr ojecte d t hera pe utic d ose, w hile als o brac keti n g t he e x pecte d cli nicall y effecti ve 
d ose ra n ge i n h u ma ns f or cli nicall y  rele va nt p har mac ol o gical acti vity a n d pr o vi di n g safet y 
c o vera ge f or a wi de ra n ge of P F-0 7 8 5 3 5 7 8 d oses .
Assess me nt of t he safet y,  t olera bilit y, a n d P K after eac h si n gle d ose le vel will be c o n d ucte d 
bef ore escalati n g t o t he ne xt d ose le vel. T he d ose/e x p os ure-escalati o n i ncre me nts are pla n ne d 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
t o be u p t o a p pr o xi mate se mi-l o garit h mic i ncreases i n e x p os ure fr o m t he pre vi o us hi g hest 
d ose le v el t hat has bee n e val uate d. If e x p os ure e xcee ds t he pr ojecte d t hera pe utic ra n ge, or if 
c ha n ges i n safet y para meters are o bser ve d, s maller d ose -escalati o n ste ps ma y be 
i m ple me nte d.
T he act ual d ose le vels, tar get e x p os ures, a n d/ or d ose le vel i ncre me nts ma y  be a dj uste d 
( hi g her or l o wer) d uri n g t he st u d y base d o n e mer gi n g h u ma n safety, t olera bilit y , a n d P K 
data, b ut pr ojecte d e x p os ures will n ot e xcee d t he pre defi ne d h u ma n e x p os ure li mits. D ose 
le vels ma y als o be re peate d if warra nte d. 
W he n t he assess me nt of t he effect of f o o d o n t he P K of P F - 0 7 8 5 3 5 7 8 is c o n d ucte d, t he d ose 
le vel will be selecte d base d o n e mer gi n g safety, t olera bilit y, a n d P K data fr o m pre vi o us 
peri o ds of t his st u d y . T he act ual d ose le vel use d will be e x pecte d t o ac hie ve e x p os ures 
si milar t o or greater t ha n pr ojecte d t hera pe utic e x p os ures (as o utli ne d i n Secti o n 4. 3. 2 ).
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.
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 pa rtici pati o n i n t he st u d y is c o nsi dere d 
a p pr o priate. All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het her a partic ular partici pa nt is s uita ble f or t his pr ot oc ol.
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:
A ge a n d Se x :
1.
Male a n d fe male partici pa nts of n o n -c hil d beari n g p ote ntial a ge d 1 8 t o 6 5 years at 
scree ni n g w h o are o vertl y healt h y as deter mi ne d b y me dical e val uati o n i ncl u di n g 
me dical hist or y , p h y sical e xa mi nati o n, la b orat or y tests, a n d car diac m o nit ori n 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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Ot h er I ncl usi o n Criteri a : 
2.
B MI of 1 6 t o 3 0. 5 k g/ m 2; a n d a t otal b o dy wei g ht > 5 0 k g ( 1 1 0 l b).
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 A p pe n di x 1 , 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 IC D a n d i n 
t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y  si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl udi n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve tes ti n g f or HI V , 
H Bc A b, H Bs A g, or H C V A b. He patitis B vacci nati o n is all o we d.
2.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y t hat ma y i ncrease t he ris k of
st u d y partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt 
i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
3.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d d ietar 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 or str o n g C Y P 3 A i n d ucers or i n hi bit ors 
w hic h are pr o hi bite d wit hi n 1 4 da y s pl us 5 half -li ves pri or t o t he first d ose of st u d y 
i nter ve nti o n. ( Refer t o Secti o n 6. 9 f or a d diti o nal details).
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
4.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y i nter ve nti o n use d i n t his st u d y  ( w hic he ver is l o n ger). P artici pati o n i n 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d uri n g t heir 
partici pati o n i n t his st u d y.
Di a g n ostic Assess me nts:
5.
A p ositi ve uri ne dr u g test .
6.
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. 
7.
Re nal i m pair me nt as defi ne d b y  a n eG F R i n a d ults of < 7 5 m L / mi n/ 1. 7 3 m². Base d 
u p o n pa rtici pa nt a ge at scree ni n g, e G F R is calc ulate d usi n g t he rec o m me n de d 
C K D -E PI  e q uati o ns i n Secti o n 1 0. 7. 2 t o deter mi ne eli gi bilit y a n d t o pr o vi de a 
baseli ne t o q ua ntif y  a ny s u bse q ue nt ki d ne y  safet y e ve nts. F or eli gi bilit y  assess me nt 
base d u p o n esti mate d re nal f u ncti o n, t he hi g her of t he scree ni n g a n d baseli ne e G F R 
val ues ma y  be use d.
8.
He mat uria as defi ne d b y > 1 + he me o n uri ne di pstic k.
9.
Al b u mi n uria as defi ne d b y al b u mi n/ cr eati ni ne rati o o n s p ot uri nal y sis > 3 0 m g/ g.
1 0. St a n dar d 1 2 -lea d E C G t hat de m o nstrates cli nicall y rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms,
c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate- a ge m y ocar dial i nfarcti o n, S T-T 
i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d- or t hir d - de gree A V
bl oc k, or seri o us bra d yarr h yt h mias or tac h ya rr hyt h mias). If Q TcF e xcee ds 4 5 0 ms, or 
Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 
3 Q Tc F or Q R S val ues use d t o deter mi ne t he partici pa nt’s eli gi bilit y .
C o m p uter -i nter prete d E C Gs s h o ul d be o verrea d by a p h ysicia n e x perie nce d i n 
rea di n g E C Gs bef ore e xcl u di n g a partici pa nt.
1 1. Partici pa nt s wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
scree ni n g, as assesse d by t he st u d y -s pecific la b orat or y a n d c o nfir me d by a si n gle 
re peat test, if dee me d necessar y: 

A L T, A S T, Bilir u bi n ≥1. 0 5 × U L N. Partici pa nts wit h a n ele vate d t otal bilir u bi n 
c o nsiste nt wit h Gil bert ’s Disease m a y ha ve a dir ect 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.

T otal c h olester ol, tri gl y ceri des, or direct L D L ≥1. 2 5 × U L N.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Ot her E xcl usi o n Criteri a :
1 2. 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 3. Use of t o bacc o or nic oti ne-c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nt of 
5 ci garettes/ da y or 2 c he ws of t o bacc o/ d a y .
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.
5. 3. Lifest yle C o nsi der ati o ns
T he f oll o wi n g g ui deli nes are pr o vi de d:
5. 3. 1. C o ntr ace pti o n
T he i n vesti gat or or t heir desi g nee, i n c o ns ultati o n wit h t he partici pa nt, will c o nfir m t hat t he 
partici pa nt is utilizi n g a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual partici pa nt 
a n d t heir part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see A p pe n di x 4 ,
Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. T he i n vesti gat or or desi g nee will a d vise t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  inter 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 nt s m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt water) at least 1 0 h o urs 
pri or t o c ollecti o n of cli nical safety la bs a n d t he pre -d ose P K sa m pl e as i n dicate d o n 
t he S o A . A d diti o nal u nsc he d ule d cli nical la b orat or y meas ure me nts s h o ul d be 
o btai ne d after t he partici pa nt has a bstai ne d fr o m all f o o d a n d dri n k (e xce pt water) f or 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
at least 4 h o urs, e xce pt f or t he fasti n g li pi d pa nel w hic h s h o ul d still be o btai ne d after 
t he partici pa nt has a bstai ne d fr o m all f o o d a n d dri n k (e xce pt water) f or at least 
1 0 h o urs , u nless la b orat or y meas ure me nts are nee de d m ore ur ge ntl y  f or percei ve d 
safety iss ues .

N o ncaffei nate d dri n ks (e xce pt gra pefr uit or gra pefr uit -relate d citr us fr uit j uices (see 
bel o w) ma y  be c o ns u me d wit h meals a n d t he e ve ni n g s nac k.

L u nc h will be pr o vi de d a p pr o xi matel y  4 h o urs after d osi n g .

Di n ner will be pr o vi de d a p pr o xi matel y  9 t o 1 0 h o urs after d osi n g.

A n e ve ni n g s nac k m a y be per mitte d .

O n n o n -d osi n g da y s w hile i n patie nt, as a p pr o priate, sta n dar d m or ni n g meal, l u nc h, 
a n d e ve ni n g meal (al o n g wit h a n e ve ni n g s nac k) are t o be pr o vi de d at a si milar cl oc k 
ti me t o t he cl oc k ti me w he n t hese meals are offere d o n t he d osi n g da y.

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi ne, gra pefr uit , or gra pefr uit -relate d 
citr us fr uits (e g, Se ville ora n ges, p o mel os, fr uit j uices) fr o m 7 d a y s pri or t o t he first 
d ose of st u d y i nter ve nti o n u ntil c ollecti o n of t he fi nal P K bl o o d sa m ple. 

W hile partici pa nts are c o nfi ne d, t heir t otal dail y  n utriti o nal c o m p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat, a n d 1 5 % pr otei n , wit h t he e xce pti o n of 
d osi n g da y s i n w hic h a hi g h-fat/ hi g h-cal orie meal will be gi ve n pri or t o st u d y  
i nter ve nti o n. T he daily 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.

D osi n g u n der faste d c o n diti o ns:
o
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 st u d y  
i nter ve nti o n.
o
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. Water 
ma y  be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur after d osi n g.

D osi n g u n der fe d c o n diti o ns:
o
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 s h o ul d start 
brea kfast a p pr o xi matel y  3 0 mi n utes pri or t o a d mi nistrati o n of st u d y 
i nter ve nti o n.
o
T he brea kfast will be c o ns u me d o ver a p pr o xi matel y a 2 0 -mi n ute peri o d wit h 
st u d y i nter ve nti o n a d mi nistere d a p pr o xi matel y 1 0 mi n utes after c o m pleti o n of 
t he meal at 0h .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
o
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. Water 
ma y  be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur after d osi n g.
o
T he brea kfast will be a hi g h -fat (a p pr o xi matel y 5 0 % of t otal cal oric c o nte nt of 
t he meal), hi g h-cal orie (a p pr o xi matel y 8 0 0 t o 1 0 0 0 cal ories) meal. T he meal 
will c o nsist of a p pr o xi matel y  1 5 0 pr otei n cal ories, 2 5 0 car b o hy drate cal ories, 
a n d 5 0 0 -6 0 0 fat cal ori es. A n e xa m ple test meal w o ul d be: 2 e g gs frie d i n b utter, 
2 stri ps of bac o n ( or 5 0 g of meat or sa usa ge), 2 slices of t oast wit h b utter, 
4 o u nces (a p pr o xi matel y  1 1 2 gra ms) of has h br o w n p otat oes, a n d 8 fl ui d o u nces 
( 2 4 0 m L) of w h ole mil k.
5. 3. 3. C affei ne, Alc o h o l, a n d T o b acc o

Partici pa nt s will a bstai n fr o m caffei ne-c o ntai ni n g pr o d ucts f or 2 4 h o urs pri or t o t he 
start of d osi n g u ntil c ollecti o n of t he fi nal P K sa m ple of eac h st u d y  peri o d. 

Partici pa nt s will a bstai n fr o m alc o h ol f or 2 4 h o urs pri or ( or as s pecifie d a b o ve f or re d 
wi ne) t o a d missi o n t o t he C R U a n d c o nti n ue a bstai ni n g fr o m alc o h ol u ntil c ollecti o n 
of t he fi nal P K sa m ple of eac h st u d y peri o d . Partici pa nt s ma y u n der g o a n alc o h ol 
breat h test or bl o o d alc o h ol test at t he discreti o n of t he i n vesti gat or.

Partici pa nt s will a bstai n fr o m t he use of t o bacc o- or nic oti ne -c o ntai ni n g pr o d ucts f or 
2 4 h o urs pri or t o d osi n g a n d d uri n g c o nfi ne me nt i n t he C R U.
5. 3. 4. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea v y lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c ollecti o n f or cli nical 
la b orat or y tests. Wal ki n g at a n or mal pace will be per mitte d;

I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P , p ulse rate , a n d 
E C G meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 
4 h o urs after d osi n g;

Partici pa nt s will be c o nfi ne d t o t he pr oce d ure r o o m f or t he first 4 h o urs after d osi n g 
o n Da y 1 of eac h peri o d d uri n g c o nti n u o us car diac m o nit ori n g, e xce pt t o use t he 
bat hr o o m. After t his, if t he e q ui p me nt set u p all o ws, partici pa nt s ma y be a m b ulat or y 
d uri n g t he E C G m o nit ori n g peri o d, b ut s h o ul d n ot e n ga ge i n stre n u o us acti vities. I f 
e qui p me nt d oes n ot all o w a m b ulati o n, a p pr o priate acc o m m o dati o ns will be ma de b y 
t he i n vesti gat or site t o facilitate c o nti n u o us m o nit ori n g (e g, be dsi de uri nals s h o ul d be 
pr o vi de d t o acc o m m o date partici pa nt s’ e xcret or y nee ds).
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 .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y be 
rescree ne d. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal a n d n o ni n vesti gati o nal me dici nal 
pr o d ucts/a u xiliar y  me dici nal pr o d ucts, me dical de vices, a n d ot her i nter ve nti o ns (e g, s ur gical 
a n d be ha vi oral) i nte n de d t o be a d mi nistere d t o t he st u d y  partici pa nts d uri n g t he st u d y 
c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o:

P F - 0 7 8 5 3 5 7 8;

Place b o f or P F -0 7 8 5 3 5 7 8.
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 7 8 5 3 5 7 8
Place b o
T y pe
Dr u g
Dr u g
Use
E x peri me ntal
Place b o
I M P or 
NI M P/ A x M P
I M P
I M P
D ose F or m ul ati o n
B ul k p o w der f or e xte m p ora ne o us pre parati o n 
of oral s ol uti o ns a n d s us pe nsi o ns
B ul k p o w der f or e xte m p ora ne o us pre parati o n 
of oral s ol uti o ns a n d s us pe nsi o ns
U nit D ose 
Stre n gt h(s)
0. 1 -5 0 0 m g
0 m g
D os a ge Le vel(s)
Si n gle asce n di n g d oses 0. 1 -5 0 0 m g (see 
Secti o n 1. 2 a n d Secti o n 4. 3. 4 )
0 m g
R o ute of 
A d mi nistr ati o n
Oral
Oral
S o urci n g
Pr o vi de d b y t he s p o ns or
Pr o vi de d 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 
p o w der f or e xte m p ora ne o us pre parati o n of 
oral s ol uti o ns a n d s us pe nsi o ns. Eac h 
c o ntai ner will be la bele d as re q uire d per 
c o u ntr y re q uire me nt.
St u d y i nter ve nti o n will be pr o vi de d i n b ul k 
p o w der f or e xte m p ora ne o us pre parati o n of 
oral s ol uti o ns a n d s us pe nsi o ns. Eac h 
c o ntai ner will be la bele d as re q uire d per 
c o u ntr y re q uire me nt.
S R S D
I B
I B
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
St u d y Ar m(s)
A r m  Title
C o h ort 1
C o h ort 2
C o h ort 3 ( O pti o nal)
A r m  Descri pti o n
Partici pa nts will recei ve 
u p t o 4 d ose le vels of 
P F -0 7 8 5 3 5 7 8 a n d u p t o 
2 d ose le vels of 
matc hi n g place b o. 
D oses will be 
a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns 
as escalati n g si n gle 
d oses t o be deter mi ne d.
Partici pa nts will recei ve 
u p t o 4 d ose le vels of 
P F -0 7 8 5 3 5 7 8 a n d u p t o 
2 d ose le vels of 
matc hi n g place b o. 
D oses will be 
a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns 
as escalati n g si n gle 
d oses t o be deter mi ne d.
Partici pa nts will recei ve 
u p t o 4 d ose le vels of 
P F -0 7 8 5 3 5 7 8 a n d u p t o 
2 d ose le vels of 
matc hi n g place b o. 
D oses will be 
a d mi nistere d as oral 
s ol uti o ns or s us pe nsi o ns 
as escalati n g si n gle 
d oses t o be deter mi ne d.
P F -0 7 8 5 3 5 7 8 a n d place b o will be pr o vi de d b y Pfizer 
 

P F -0 7 8 5 3 5 7 8 or place b o l o w d osa ge stre n gt h oral s ol uti o n s will be e xte m p ora ne o usl y 
pre pare d f or si n gle oral d oses 
.

P F - 0 7 8 5 3 5 78 or place b o oral s us pe nsi o n s will be e xte m p ora ne o usl y  pre pare d f or 
si n gle oral d oses 
.

P F -0 7 8 5 3 5 7 8 or place b o 
 oral s ol uti o n s will be e xte m p ora ne o usl y pre pare d f or 
si n gle oral d oses 
.
P F -0 7 8 5 3 5 7 8 a n d place b o will be prese nte d t o t he partici pa nts i n i n di vi d ual d osi n g 
c o ntai ners.
6. 1. 1. A d mi nistr ati o n
F or faste d peri o ds:

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 st u d y  
i nter ve nti o n at a p pr o xi matel y 0 8: 0 0 h o urs ( pl us or mi n us 2 h o urs) wit h o ut brea kfast 
o n Da y  1.
F or fe d peri o d(s):

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 brea kfast 
a p pr o xi matel y 3 0 mi n utes pri or t o d osi n g o n Da y 1 w hic h is t o be c o m plete d wit hi n 
a p pr o xi matel y 2 0 mi n utes as o utli ne d i n Secti o n 5. 3. 2 . T he partici pa nts will t he n 
recei ve st u d y i nter ve nti o n a p pr o xi matel y 1 0 mi n utes after c o m pleti o n of t he meal at 
a p pr o xi matel y 0 8: 0 0 h o urs ( pl us or mi n us 2 h o urs).
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
F or all peri o ds, i n vesti gat or site pers o n nel will a d mi nister a si n gle oral d ose of st u d y  
i nter ve nti o n o n Da y 1 of eac h peri o d wit h a m bie nt te m perat ure water t o a t otal v ol u me of 
a p pr o xi matel y 2 40 m L. St u d y  i nter ve nti o n will be a d mi nistere d acc or di n g t o t he E D R.
A d mi nistrati o n of st u d y  i nterve nti o n(s) will be perf or me d b y  a n a p pr o priatel y q ualifie d a n d 
trai ne d me m ber of t he st u d y staff as all o we d b y l ocal, state, a n d i nstit uti o nal g ui da nce. 
F oll o wi n g a d mi nistrati o n of st u d y i nter ve nti o n(s) at t he site, partici pa nts will be o bser ve d f or 
u p t o 2 h o urs p ost -d ose b y a n a p pr o priatel y q ualifie d a n d trai ne d me m ber of t he st u d y staff. 
A p pr o priate me dicati o n a n d ot her s u p p orti ve meas ures f or ma na ge me nt of a me dical 
e mer ge nc y will be a vaila ble i n acc or da nce wit h l ocal g ui deli nes a n d i nstit uti o nal g ui deli nes.
6. 2. Pre p ar ati o n , H a n dli n g , St or a ge , a n d Acc o u nt a bilit y
1.
T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate c o n diti o ns (e g, 
te m perat ure) ha ve bee n mai ntai ne d d uri n g tra nsit f or all st u d y  i nter ve nti o ns recei ve d 
a n d a n y discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y  i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y, pre pare, a n d/or a d mi nister st u d y  i nter ve nti o n.
3.
All st u d y  i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d 
m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d 
st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. At 
a mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures si nce pre vi o usly d oc u me nte d u p o n 
ret ur n t o b usi ness.
4.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h acti o ns ta ke n. T he site s h o ul d acti vely 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o o n as p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y i nter ve nti o n m ust be 
q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  
i nter ve nti o n. S pecific details re gar di n g t he e xc ursi o n defi niti o n a n d i nf or mati o n t o
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he C R U 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 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 site pr oce d ures. All destr ucti o n m ust be 
a de q uately d oc u me nte d. If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or 
site, t he i n vesti gat or m ust e ns ure t hat t he materials are destr oye d i n c o m plia nce wit h 
a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns 
pr o vi de d b y Pfizer.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y t he s p o ns or w it hi n 1 b usi ness da y  of 
disc o ver y .
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a d mi nistrati o n or dis pe nsi n g t o t he partici pa nt b y  q ualifie d 
staff. Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mita nt treat me nts, 
a n d acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healt hcare pr o vider, 
partici pa nt , i n acc or da nce wit h t his pr ot oc ol. Local healt h a ut h orit y re g ulati o ns or 
i n vesti gat or site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
P F - 07 8 5 3 5 7 8 a n d place b o oral d osi n g s ol uti o ns/s us pe nsi o ns will be pre pare d i n t he C R U b y  
2 o perat ors, 1 of w h o m is a p har macist. Details of d ose pre parati o n will be gi ve n i n a 
se parate E D R. Pre pare d d oses will be pr o vi de d i n u nit d ose c o ntai ners a n d la bele d i n 
acc or da nce wit h Pfizer re g ulati o ns a n d t he i n vesti gat or site’s la beli n g re q uire me nts .
P F - 0 7 8 5 3 5 7 8 a n d place b o will be pre pare d b y q ualifie d u n bli n de d site pers o n nel acc or di n g 
t o t he IP M . Bli n de d st u d y i nter ve nti o n will be a d mi nistere d i n a bli n de d fas hi o n t o t he 
partici pa nt . 
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 ned 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 d o u ble -bli n d (s p o ns or-u n bli n de d) st u d y . 
6. 4. 1. Bli n di n g of P a rtici p a nts
Partici pa nts will be bli n de d t o t heir assi g ne d st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
6. 4. 2. Bli n di n g of Site Pers o n nel
I n vesti gat ors a n d ot her site staff will be bli n de d t o partici pa nts’ assi g ne d st u d y i nter ve nti o n.
Partici pa nts will be assi g ne d t o recei ve st u d y i nter ve nti o n acc or di n g t o t he assi g ne d treat me nt 
gr o u p fr o m t he ra n d o mizati o n sc he me. I n vesti gat ors will re mai n bli n de d t o eac h partici pa nt’s 
assi g ne d st u d y i nter ve nti o n t hr o u g h o ut t he c o urse of t he st u d y . 
I n or der t o mai ntai n t his bli n d, a n ot her wise u ni n v ol ve d t hir d party will be res p o nsi ble f or t he 
pre parati o n a n d dis pe nsi n g of all st u d y  i nter ve nti o n a n d will e n dea v or t o e ns ure t hat t here are 
n o differe nces i n ti me ta ke n t o dis pe nse or vis ual prese ntati o n, f oll o wi n g ra n d o mizati o n or 
dis pe nsi n g. T his t hir d part y  will i nstr uct t he partici pa nt t o a v oi d disc ussi n g t he taste, d osi n g 
fre q ue nc y, or pac ka gi n g of t he st u d y i nter ve nti o n wit h t he i n vesti gat or. 
I n t he e ve nt of a q ualit y ass ura nce a u dit, t he a u dit or(s) will be all o we d access t o u n bli n de d 
st u d y i nter ve nti o n rec or ds at t he site(s) t o verif y t hat ra n d o mizati o n/ dis pe nsi n g has bee n d o ne 
acc uratel y.
P C R U p har mac y  staff res p o nsi ble f or pre pari n g all st u d y i nter ve nti o ns will be u n bli n de d. 
P C R U site staff pr o vi di n g tec h nical s ys te m s u p p ort t o p har mac y staff a n d s u p p orti n g bli n de d 
la b orat or y data pr ocesses will be u n bli n de d. T hese site staff pr o vi di n g sys te m s u p p ort will 
n ot be i n v ol ve d i n a n y  data c ollecti o n or cli nic fl o or acti vities.
6. 4. 3. Bli n di n g of t he S p o ns or
As t his is a s p o ns or-o pe n st u d y, t he s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data 
d uri n g t he c o urse of t he st u d y  f or t he p ur p ose of safety assess me nt, facilitati n g 
d ose -escalati o n d ecisi o ns, 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. U n bli n de d res ults will be re vie we d b y  a desi g nate d li mite d n u m ber of s p o ns or 
c ollea g ues wit hi n t he st u d y  tea m.
6. 4. 4. Se nsiti ve Cli nic al D at a
Se nsiti ve cli nical data are data c o llecte d i n t his st u d y t hat ha ve t he p ote ntial t o u n bli n d a 
partici pa nt’s treat me nt assi g n me nt. Access t o se nsiti ve cli nical data will be restricte d t o 
a ut h orize d i n di vi d uals u ntil t he st u d y has bee n u n bli n de d. T he f oll o wi n g data varia bles are 
c o nsi dere d se nsiti ve cli nical data:

St u d y  i nter ve nti o n assi g n me nts ( P F-0 7 8 5 3 5 7 8 or place b o );

P K data.
6. 4. 5. Bre a ki n g t he Bli n d
T he met h o d f or brea ki n g t he bli n d i n t his st u d y  will be ma n ual. I n case of a n e mer ge nc y, t he 
i n vesti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a partici pa nt’s
treat me nt assi g n me nt is warra nte d. Partici pa nt safet y m ust al wa ys be t he first c o nsi derati o n 
i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci des t hat u n bli n di n g is warra nte d, t he 
i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he st u d y me dical m o nit or pri or t o 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
u n bli n di n g a partici pa nt’s treat me nt assi g n me nt u nless t his c o ul d dela y  f urt her ma na geme nt
of t he partici pa nt. If a partici pa nt’s treat me nt assi g n me nt is u n bli n de d, t he s p o ns or m ust be 
n otifie d wit hi n 2 4 h o urs after brea ki n g t he bli n d. W he n t he bli n di n g c o de is br o ke n, t he 
reas o n m ust be f ully d oc u me nte d a n d e ntere d o n t he C R F.
Bl o o d s peci me ns will be o btai ne d fr o m all partici pa nts f or P K a nal ys is t o mai ntai n t he st u d y 
bli n d at t he i n vesti gat or site. O nl y  t he i n vesti gat or site staff a n d bli n de d st u d y  m o nit or, if 
assi g ne d, will be bli n de d t o st u d y  treat me nt. Ot her Pfizer pers o n nel will be u n bli n de d t o 
partici pa nt treat me nts i n or der t o per mit real-ti me i nter pretati o n of t he safet y a n d P K data; 
a n d pr o vi de i nf or mati o n necessar y  t o p ote ntiall y alter t he d ose-escalati o n se q ue nce. T he 
bli n de d st u d y m o nit or, if assi g ne d, will re mai n bli n de d t o treat me n t u ntil all m o nit ori n g f or 
t he st u d y has bee n c o m plete d. S peci me ns fr o m partici pa nt s ra n d o mize d t o place b o will n ot 
be r o uti nel y a nal yz e d. T o mi ni mize t he p ote ntial f or bias, treat me nt ra n d o mizati o n 
i nf or mati o n will be ke pt c o nfi de ntial by Pfizer u n bli n de d pers o n nel a n d will n ot be release d 
t o t he bli n de d i n vesti gat or or bli n de d i n vesti gat or site pers o n nel u ntil t he st u d y data base has 
bee n l oc ke d or t he i n vesti gat or re q uests u n bli n di n g f or safet y reas o ns.
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n t he i n di vi d ual d o se 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 vestigat or or desi g nee, u n der me dical s u per visi o n. T he date a n d ti me of eac h d ose 
a d mi nistere d i n t he cli nic will be rec or de d i n t he s o urce d oc u me nts a n d rec or de d i n t he C R F. 
T he d ose of st u d y i nter ve nti o n a n d st u d y partici pa nt i de ntificati o n will be c o nfir me d at t he 
ti me of d osi n g by a me m ber of t he st u d y site staff ot her t ha n t he pers o n a d mi nisteri n g t he 
st u d y i nter ve nti o n. St u d y site pers o n nel will 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
T he decisi o n t o pr ocee d t o t he ne xt d ose le vel of P F - 0 7 8 5 3 5 7 8 (eit her a n i ncrease, decrease , 
or re peat of a pre vi o us d ose le vel ) will be ma de b y t he st u d y tea m a n d t he i n vesti gat or base d 
o n safet y, t olera bilit y, a n d preli mi nar y P K data o btai ne d at t he pri or d ose le vel. At least 
6 partici pa nts (i ncl u di n g at least 1 place b o partici pa nt) m ust c o m plete t he pri or d ose le vel. 
P K data t hr o u g h at least 2 4 h o urs p ost- d ose a n d safet y a n d t olera bilit y data t hr o u g h at least
4 8 h o urs p ost -d ose of t he c urre nt peri o d will be re vie we d. C u m ulati ve safet y  a n d t olera bilit y 
fr o m all pre vi o us peri o ds will als o be re vie we d.
T he d osi n g sc he d ule ma y als o be a dj uste d t o e x pa n d a d osi n g c o h ort t o f urt her e val uate
safety, t olera bilit y, a n d/ or P K fi n di n gs at a gi ve n d ose le vel or t o a dd c o h orts t o e val uate
a d diti o nal d ose le vels or re peat d ose le vels . T he st u d y  pr oce d ures f or t hese a d diti o nal 
partici pa nt(s)/c o h ort(s) will be t he sa me as t hat descri be d f or ot her st u d y partici pa nts/c o h orts.
Preca uti o nar y  se nti nel d osi n g will be use d i n t his st u d y. T w o partici pa nts ( 1 recei vi n g 
P F -0 7 8 5 3 5 7 8 a n d 1 recei vi n g place b o) wit hi n a peri o d will be d ose d i nitiall y bef ore t he 
re mai ni n g partici pa nts of t hat peri o d are d ose d. Safet y a n d t olera bilit y data t hr o u g h at least 
2 4 h o urs p ost - d ose f or t he se nti nel partici pa nts will be re vie we d pri or t o d osi n g t he 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
re mai ni n g partici pa nts of t hat peri o d. Se nti nel d osi n g ma y be o mitte d w he n re peati n g a d ose 
le vel or a d mi nisteri n g a l o wer d ose le vel t ha n pre vi o usl y e val uate d.
6. 6. 1. D ose Esc al ati o n a n d St o p pi n g R ules 
D ose escalati o n st o p pi n g r ules will be use d t o deter mi ne w het her t he ma xi mal t olerate d d ose 
has bee n attai ne d. D ose escalati o n ma y  be st o p pe d if it is deter mi ne d t hat t he li mits of safet y 
a n d/ or t olera bilit y ha ve bee n reac he d. T his decisi o n will be ma de after a disc ussi o n ta kes 
place bet wee n t he s p o ns or st u d y  tea m a n d t he i n vesti gat or. T he s p o ns or st u d y tea m ma y n ot 
o verr ule t he i n vesti gat or’s decisi o n t o st o p d ose escalati o n. If d ose escalati o n is st o p pe d 
beca use of a n y of t hese criteria, a d diti o nal c o h orts ma y recei ve t he sa me or l o wer d oses of 
t he st u d y i nter ve nti o n.
T he d ose escalati o n will be ter mi nate d base d o n t he f oll o wi n g criteria:

If 5 0 % or m ore of t he partici pa nt s recei vi n g acti ve dr u g at a gi ve n d ose le vel ( b ut n ot 
partici pa nt s recei vi n g place b o) de vel o p si milar cli nicall y si g nifica nt la b orat or y, E C G, 
or vital si g n a b n or malities, i n t he sa me or ga n class, i n dicati n g d ose -li miti n g 
i nt olera nce.

Se vere n o nseri o us A Es, c o nsi dere d as, at least, p ossi bl y relate d t o st u d y i nter ve nti o n
a d mi nistrati o n, i n 2 part ici pa nts at a gi ve n d ose le vel ( b ut n ot partici pa nts recei vi n g 
place b o), i n de pe n de nt of wit hi n or n ot wit hi n t he sa me s yste m or ga n class, i n dicati n g 
d ose -li miti n g i nt olera nce.

D osi n g will be pa use d f or a n y S A E t hat occ urs i n a partici pa nt recei vi n g acti ve 
treat me nt u ntil ca usalit y is f ull y assesse d b y t he PI a n d s p o ns or. D osi n g ma y res u me 
if t he S A E is deter mi ne d t o be n ot dr u g-relate d by t he PI a n d s p o ns or. If t he S A E is 
deter mi ne d t o be eit her dr u g-relate d or u n k n o w n, eit her d osi n g will cease or t he S A E 
w ill be e val uate d by t he s p o ns or’s pr ot oc ol re vie w c o m mittee ( or si milar re vie w 
gr o u p), w hic h is i n de pe n de nt of t he st u d y  tea m a n d i n vesti gat ors. If t he pr ot oc ol 
re vie w c o m mittee deter mi nes t hat d osi n g ma y res u me, a pla n t hat miti gates ris ks t o 
partici pa nt s wit h t he res u m pti o n of d osi n g will be i m ple me nte d. S uc h a pla n c o ul d 
i ncl u de a re visi o n of i ncl usi o n/e xcl usi o n criteria, re peati n g or re d uci n g t he d ose, or 
a d di n g a p pr o priate safet y m o nit ori n g.

It is deter mi ne d t hat t he li mit of safet y a n d/ or t olera bilit y has bee n reac he d. T his 
decisi o n will be ma de f oll o wi n g disc ussi o ns bet wee n t he st u d y  tea m a n d t he 
i n vesti gat or.

Ot her fi n di n gs t hat, at t he discreti o n of t he st u d y t ea m a n d i n vesti gat or, i n dicate t hat 
d ose escalati o n s h o ul d be halte d .

If, at a n y d ose le vel, t he a vera ge e x p os ure reac hes or e xcee ds t he P K st o p pi n g li mits:
.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

If, base d o n t he o bser ve d data, t he gr o u p mea n Cma x or A U C ( base d o n t otal plas ma 
c o nce ntrati o n) of t he ne xt pla n ne d d ose is pr ojecte d t o e xcee d t he escalati o n li mits, 
t hat d ose will n ot be e x pl ore d. M o difie d d oses ma y be e x pl ore d if t he y are n ot 
e x pecte d t o e xcee d P K st o p pi n g criteria.
Pr o gressi o n t o t he ne xt d ose will occ ur if t he last d ose was well t olerate d a n d after 
satisfact or y re vie w of t he a vaila ble safety a n d P K data.
6. 7. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y partici pati o n.
6. 8. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of P F -0 7 8 5 3 5 7 8 greater t ha n 5 0 0 m g wit hi n a 2 4 -h o ur ti me peri o d 
will be c o nsi dere d a n o ver d ose.
T here is n o s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or or treati n g p hys icia n 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 o f t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E.
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 2 da ys 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 mi t a nt T her a p y
P F -0 7 8 5 3 5 7 8 is pri maril y  meta b olize d b y  
. T heref ore, 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 t hat are m o derate or str o n g 
 i n d ucers or i n hi bit ors 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. Use of all ot her 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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A n o n- e x ha usti ve list of e xcl u de d m o derate or str o n g  
 i n d ucers or i n hi bit ors is i n 
A p pe n di x 9 . Beca use t his is n ot a n all -i ncl usi ve list, site staff s h o ul d c o ns ult wit h t he s p o ns or 
or desi g nee wit h a n y q uesti o ns re gar di n g p ote ntial D DI.
Li mite d use of n o n prescri pti o n me dicati o ns t hat are n ot belie ve d t o affect partici pa nt safet y  
or t he o verall res ults of t he st u d y  ma y be per mitte d o n a case -b y -case basis f oll o wi n g 
a p pr o val b y t he s p o ns or. Aceta mi n o p he n/ paraceta m ol ma y be use d at d oses of ≤1 g/ da y .
Fe males ta ki n g H R T ma y  be eli gi ble t o partici pate i n t his st u d y if t he y are willi n g t o 
disc o nti n ue t hera p y at least 2 8 d a y s pri or t o t he first d ose of st u d y treat me nt a n d re mai n off 
h or m o nal t hera p y f or t he d urati o n of t he st u d y. 
All c o nc o mita nt treat me nts ta ke n d uri n g t he st u d y  m ust be rec or de d wit h i n dicati o n, dail y 
d ose, a n d start a n d st o p dates of a d mi nistrati o n. All partici pa nts will be q uesti o ne d a b o ut 
c o nc o mita nt treat me nt at eac h cli nic visit.
Treat me nts ta ke n wit hi n 2 8 da y s bef ore t he first d ose of st u d y i nter ve nti o n will be 
d oc u me nte d as a pri or treat me nt. Treat me nts ta ke n after t he first d ose of st u d y  i nter ve nti o n 
will be d oc u me nte d as c o nc o mita nt treat me nts.
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o nti n u ati o n of St u d y I nter ve nti o n
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue st u d y i nter ve nti o n. Reas o ns 
f or per ma ne nt di sc 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 Es or ot her 
(a d mi nistrati ve) reas o ns.  
D isc o nti n uati o n of st u d y i nter ve nti o n d oes n ot re prese nt wit h dra wal fr o m t he st u d y. If st u d y 
i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt s h o ul d re mai n i n t he st u d y t o be 
e val uate d f or o n g oi n g A Es . 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 a n d f oll o w-u p 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.
I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be d oc u me nte d o n t he 
a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is disc o nti n ui n g f urt her 
recei pt of st u dy i nter ve nti o n or als o fr o m st u d y  pr oce d ures, f urt her st u d y f oll o w-u p, a n d/ or 
f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
7. 1. 1. P ote nti al C ases of Ac ute Ki d ne y I nj ur y
Partici pa nts e x p ose d t o I M P de m o nstrati n g tra nsie nt or s ustai ne d i ncrease i n Screat ( wit h 
decrease i n Screat - base d e G F R or e Cr Cl) re q uire e x pe dite d e val uati o n t o differe ntiate A KI  
fr o m DI CI. DI CI is defi ne d as tra ns p orter- me diate d effect relate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A KI m a y  be d ue t o o ne or m ore ty pes of i nj ur y, i ncl u di n g DI KI. Differe ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y c o ns ultati o n.
F oll o w -u p Assess me nts
T he partici pa nt s h o ul d ret ur n t o t he site f or e val uati o n as s o o n as p ossi ble, prefera bl y wit hi n 
4 8 h o urs of a ware ness of t he a b n or mal res ults. 
E val uati o n s h o ul d i ncl u de p h y sical e xa mi nati o n, la b orat or y tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs a n d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates of e G F R, e Cr Cl a n d Screat -base d e G F R a n d c o m bi ne d 
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 uati o n descri be d i n 
A p pe n di x 7 .
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.
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)
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 8
A KI (i ncl u di n g DI KI)
A n y o ne of t he bel o w
DI CI
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 7 f or Gra des A 1 t o A 3 
q ua ntitati o n)
Uri ne v ol u me
Uri ne v ol u me < 0. 5 m L/ k g/ h f or 
6 c o nsec uti ve h o urs
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is 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 of t he f oll o wi n g b ullete d criteria 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 d y i nter ve nti o n. 

Q Tc F > 5 0 0 ms ec.

C ha n ge i n Q Tc F fr o m baseli ne > 6 0 msec a n d Q Tc F > 4 5 0 msec .
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. 1. 3. C O VI D - 1 9
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n A E or S A E (as 
a p pr o priate) a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. St u d y  treat me nt s h o ul d c o nti n ue 
u nless t he i n vesti gat or/treati n g p h ys icia n is c o ncer ne d a b o ut t he safety of t he partici pa nt, i n 
w hic h case te m p orar y  or per ma ne nt disc o nti n uati o n ma y be re q uire d.
It is rec o m men de d t hat t he i n vesti gat or disc uss te m p orar y  or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or. 
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al F r o m t he St u d y
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at t heir o w n re q uest. Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ure;
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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;

Discreti o n of t he i n vesti gat or or s p o ns or f or safet y or be ha vi oral reas o ns, or t he 
i na bilit y of the partici pa nt t o c o m pl y  wit h t he pr ot oc ol re q uire d sc he d ule of st u d y 
visits or pr oce d ures. 
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d . See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y. Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
T he partici pa nt will be per ma ne ntl y disc o nti n ue d fr o m t he st u d y i nter ve nti o n a n d t he st u d y  at 
t hat ti me.
If a partici pa nt wit h dra ws fr o m t he st u d y, t he y m a y  re q uest destructi o n of a n y  re mai ni n g 
sa m ples ta ke n a n d n ot teste d, a n d the i n vesti gat or m ust d oc u me nt a n y  s uc h re q uests i n t he 
site st u d y rec or ds a n d n otif y t he s p o ns or acc or di n gl y.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt (see Secti o n 7. 2. 1 f or 
discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns will be perf or me d a n d n o a d diti o nal 
data 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 nly 
e xce pti o n t o t his is w he n a partici pa nt s pecifically wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h t he m or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his i nf or mati o n. 
Partici pa nt s s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt 
fr o m f ut ure f oll o w-u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y fr o m 
f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures a n d/ or p osttreat me nt st u d y 
f oll o w-u p, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat vital stat us ( w het her 
t he par tici 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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble. Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust 
ma 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 v ale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d;

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, t he partici pa nt will be c o nsi dere d 
t o ha ve wit h dra w n fr o m t he st u d y. 
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
8. 1. A d mi nistr ati ve a n d B aseli ne Pr oce d ures
T he i n vesti gat or ( or a n a p pr o 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 nts will be scree ne d wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he st u d y i nter ve nti o n 
t o c o nfir m t hat t he y meet t he st u d y p o p ulati o n criteria f or t he st u d y. If t he ti me bet wee n 
scree ni n g a n d d osi n g e xcee ds 2 8 d a y s as a res ult of u ne x pecte d dela ys (e g, dela ye d dr u g 
s hi p me nt), t he n partici pa nts d o n ot re q uire rescree ni n g if t he la b orat or y res ults o btai ne d pri or 
t o first d ose a d mi nistrati o n meet eli gi bilit y criteria.
A partici pa nt w h o q ualifie d f or t his pr ot oc ol b ut di d n ot e nr oll fr o m a n earlier c o h ort / gr o u p
ma y  be use d i n a s u bse q ue nt c o h ort/ gr o u p wit h o ut rescree ni n g, pr o vi de d la b orat or y res ults 
o btai ne d pri or t o t he first d ose a d mi nistrati o n meet eli gi bilit y  criteria f or 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 o llecti o ns (e g, retai ne d researc h sa m ples)
ma y  n ot nee d t o be re peate d , as a p pr o priate.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A partici pa nt w h o q ualifi e d f or t his pr ot oc ol, c o m plete d Da y  - 1 pr oce d ures a n d assess me nts, 
a n d was n o t d ose d as o ne of t he first 2 se nti nel partici pa nts i n a peri o d m a y  be d ose d after t he 
st u d y re q uire d mi ni m u m 2 4-h o ur pa use wit h o ut re p eati n g Da y  - 1 pr oce d ures a n d 
assess me nts as l o n g as n o m ore t ha n 4 8 h o urs se parate Da y  -1 a n d Da y  1. 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 resea rc h sa m ples) ma y  be use d 
wit h o ut re peat c ollecti o n, as a p pr o priate.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u msta nces outsi de t he c o ntr ol of t he i n vesti gat or t hat ma ke it u nfeasi ble t o perf or m t he 
test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
well -bei n g of t he partici pa nt . W he n a pr ot oc ol-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
A n y  safet y, la b orat or y, or a nalyt e res ults t hat ha ve bee n c ollecte d f or t he p ur p oses of t his 
st u d y a n d c o ul d u n bli n d t he st u d y will n ot be re p orte d t o i n vesti gati ve sites or ot her bli n de d 
pers o n nel u ntil t he st u d y  has bee n u n bli n de d.
If d o ne ar o u n d t he ti me of a bl o o d dra w, E C Gs a n d vital si g n assess me nts ( B P a n d p ulse rate) 
s h o ul d be c ollecte d bef ore t he bl o o d dra w. 
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 nts i n t his st u d y  is a p pr o xi matel y 
4 0 0 m L . T he act ual c ollecti o n ti mes of bl o o d sa m pli n g ma y c ha n ge. A d diti o nal bl o o d 
sa m ples ma y be ta ke n f or safety assess me nts at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal 
v ol u me ta ke n d uri n g t he st u d y  d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d of 5 6 c o nsec uti ve 
da y s.
T o pre pare f or st u d y partici pati o n, partici pa nts will be i nstr ucte d o n t he i nf or mati o n i n t he 
Lifest y le C o nsi derati o ns a n d Pri or a n d C o nc o mita nt T hera p y secti o ns of t he pr ot oc ol.
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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 3. 1. P h ysic al E x a mi n ati o ns
A c o m plete P E 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 yste ms. 
A brief P E 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 s ys te ms, a n d partici pa nt -re p orte d s ym pt o ms.
P Es ma y  be c o n d ucte d b y a p h ysicia n, trai ne d p h ysicia n’s assista nt, or n urse practiti o ner as 
acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets s o t hat o nl y 
li g ht cl ot hi n g re mai ns. The 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 
a n d will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. A n y u nt o war d p h ys ical 
e xa mi nati o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8. 4. 1 t o 8. 4 . 3.
8. 3. 2. Ne ur ol o gic al E x a mi n ati o ns
Ne ur ol o gical e xa mi nati o ns ma y  be c o n d ucte d by a p h ysicia n, trai ne d p h ysicia 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 at t he n o mi nal ti me p oi nts 
s pecifie d i n t he S o A . T he ne ur ol o gical e xa m will c o nsist of assess me nt of hi g her c ortical 
f u ncti o n, t he cra nial ner ves, m ot or f u ncti o n, dee p te n d o n refle xes, se ns or y e xa m, a n d 
c o or di nati o n a n d gait. A d diti o nal ne ur ol o gical e xa mi nati o ns t hat are o utsi de of S o A (e g, t o 
e val uate a n A E) ma y be c o n d ucte d at t he discreti o n of i n vesti gat or. All ne ur ol o gical e xa ms 
s h o ul d be d o ne t o t he e xte nt nee de d t o assess t he partici pa nt f or a n y  p ote ntial c ha n ges i n 
ne ur ol o gical stat us, as deter mi ne d b y  t he i n vesti gat or ( or desi g nee). 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 t he ne ur ol o gical e xa mi nati o ns ma y  occ ur base d o n e mer gi n g data.
8. 3. 3. Vit al Si g ns
8. 3. 3. 1. Bl o o d Press ure a n d P ulse R ate
S u pi ne B P will be meas ure d wit h t he partici pa nt’s ar m s u p p orte d at t he le vel of t he heart a n d 
rec or de d t o t he nearest m m H g after a p pr o xi matel y 5 mi n utes of rest. T he sa me ar m 
( prefera bly t he d o mi na nt ar m) will be use d t hr o u g h o ut t he st u d y . Partici pa nts s h o ul d be 
i nstr ucte d n ot t o s pea k d uri n g meas ure me nts. W he n tri plicate meas ure me nts of s u pi ne B P or 
p ulse rate are re q uire d per S o A , meas ure me nts s h o ul d be c ollecte d 2-4 mi n utes a part.
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 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 uls e rate will be 
per mitte d, as necessar y, t o e ns ure a p pr o priate c ollecti o n of safet y  data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4 . 3.
8. 3. 3. 2. Res pir at or y R ate
Res pirat or y  rate will be meas ure d after a p pr o xi matel y 5 mi n utes rest i n s u pi ne p ositi o n b y
o bser vi n g a n d c o u nti n g t he res pirati o ns of t he partici pa nt f or 3 0 sec o n ds a n d m ulti plie d b y  2.
W he n B P is t o be ta ke n at t he sa me ti me, res pirati o n meas ure me nt will be d o ne d uri n g t he 
5 mi n utes of rest a n d bef ore B P meas ure me nt.
8. 3. 4. Electr oc ar di o gr a m s
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 pe rf 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. 
Tri plicate 1 2 -lea d E C Gs will be o btai ne d a p pr o xi matel y 2- 4 mi n utes a part; t he a vera ge of t he 
tri plicate E C G meas ure me nts c ollecte d at - 1. 0, - 0. 5, a n d 0 h o urs pre-d ose o n Da y 1 of eac h 
peri o d will ser ve as eac h partici pa nt’s baseli ne Q Tc F val ue f or t hat peri o d. 
T o e ns ure safet y of t he partici pa nts, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o baseli ne meas ure me nts fr o m t he c urre nt peri o d. A d diti o nal E C G m o nit ori n g 
will occ ur if a) t he mea n val ue fr o m t he tri plicate meas ure me nts f or a n y p ost-d ose Q Tc F
i nter val is i ncrease d by ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms; or b) a n a bs ol ute Q T val ue 
is ≥5 0 0 ms f or a n y  sc hed ule d E C G. If eit her of t hese c o n diti o ns occ urs, t he n a si n gle E C G 
meas ure me nt m ust be re peate d at least h o url y u ntil Q Tc F 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.
F or si n gle E C G c ollecti o ns, a d di ti 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 by ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms; or b) a n a bs ol ute Q T val ue 
is ≥5 0 0 ms f or a n y  sc he d ule d E C G. If eit her of t hese c o n diti o ns occ urs, t he n 2 a d diti o nal 
E C Gs will be c olle cte d a p pr o xi matel y 2 t o 4 mi n utes a part t o c o nfir m t he ori gi nal 
meas ure me nt. If t he Q Tc F val ues fr o m t hese re peate d E C Gs re mai n a b o ve t he t hres h ol d 
val ue, t he n a si n gle E C G m ust be re peate d at least h o url y  u ntil Q Tc val ues fr o m 2 s uccessi ve 
E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat meas ure me nt.
If a) a p ost d ose Q Tc F i nter val re mai ns ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a 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
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 u rs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y. It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne-rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o vi der’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 8 .
8. 3. 4. 1. C o nti n u o us C ar di ac M o nit ori n g b y Tele metr y
All a b n or mal r h yt h ms will be rec or de d a n d re vie we d b y  t he st u d y p h ysicia n f or t he prese nce 
of r h yt h ms of p ote ntial cli nical c o ncer n. T he ti me, d urati o n, a n d descri pti o n of t he cli nicall y 
si g nifica nt e ve nt will be rec or de d i n t he C R F. I n a d diti o n, a pri nte d rec or d of t he traci n g(s) of 
t he cli nicall y si g nifica nt r h yt h m(s) will be ma de a n d retai ne d wit h ot her s o urce d oc u me nts.
Tele metr y  s h o ul d be c ollecte d usi n g a ce ntralize d s yste m t hat als o all o ws f or t he st ora ge a n d 
a d va nce d a nal ys is of all rec or de d data i n or der t o preser ve i m p orta nt e ve nts f or f ut ure 
e val uati o ns. H olter m o ni t ori n g s h o ul d n ot be use d i n parallel wit h c o nti n u o us tele metr y, 
u nless it is t he o nl y  mea ns of data st ora ge a vaila ble at t he i n vesti gat or site, or verifia ble 
arr h yt h mia q ua ntificati o n is re q uire d. T o esta blis h a baseli ne, tele metr y  s h o ul d be rec or de d 
f or at least 2 h o urs bef ore d osi n g i n Peri o d 1 . T his ma y be d o ne i m me diatel y pri or t o d osi n g 
or at s o me 2 -h o ur c o nti n u o us i nter val i n t he 2 4 h o urs pri or t o d osi n g, as l o n g as t he rec or di n g 
is perf or me d w he n t he partici pa nt is a wa ke. Tele metr y m a y be st o p pe d wit hi n a reas o na bl y 
s h ort peri o d of ti me pri or t o d osi n g, i n or der t o a v oi d i nterfere nce wit h st u d y o perati o ns 
c o n d ucte d i m me diatel y bef ore d osi n g. H o we ver, it is e x pecte d t hat t he tele metr y lea ds will 
be i n place a n d t he s ys te m c o n necte d pri or t o d osi n g.
8. 3. 5. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A . 
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y si g nifica nt c ha n ges occ urri n g d uri n g t he st u d y  i n t he A E secti o n of t he C R F. 
Cli nicall y si g nifica nt a b n or mal la b orat or y test fi n di n gs are t h ose t hat are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt’s c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d clinicall 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 1 4 da y s after t he last d ose of st u d y i nter ve nti o n s h o ul d be 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 vest i gat or or st u d y me dical m o nit or.
If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he i n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d a n d t he s p o ns or n otifie d.
See A p pe n di x 6 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
DI LI .
See A p pe n di x 7 f or i nstr ucti o ns f or la b orat or y testi n g t o m o nit or ki d ne y f u ncti o n a n d 
re p orti n g la b orat or y test a b n or malities.
Partici pa nt s ma y u n der g o ra n d o m uri ne dr u g testi n g at t he discreti o n of t he i n vesti gat or.
Dr u g testi n g c o n d ucte d pri or t o d osi n g m ust be ne gati ve f or partici pa nts t o recei ve st u d y 
i nter ve nti o n.
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 or ti 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, o r t he partici pa nt’s le gall y 
a ut h orize d re prese ntati ve), or t he y  ma y arise fr o m cli nical fi n di n gs of t he in vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o ass ess 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 , eac h partici pa nt will be 
q uesti o ne d a b o ut t he occ urre nce of A E s i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y Pfizer Safety t o o btai n s pecific f oll o w - u p 
i nf or mati o n i n a n e x pe dite d fas hi o n.
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g AE s a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore u n der g oi n g a n y st u d y- relate d pr oce d ure a n d/ or recei vi n g st u d y 
i nter ve nti o n), t hr o u g h a n d i ncl u di n g a mi ni m u m of 2 8 cale n dar da ys, e xce pt as i n dicate d 
bel o w , after t he last a d mi nistrati o n of t he st u d y i nter ve nti o n.
F oll o w -u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut t he acti ve c ollecti o n peri o d a n d u ntil t he 
A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 parti ci pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n
beca use of a n A E or S A E, 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 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 u salit y of AEs a n d S A E s a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A E s a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 4. 3. F oll o w - Up of A E s a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi n ati o n of 
p ossi ble ca usalit y . A ny i nf or mati o n rele va nt t o t he e ve nt, s uc h as c o nc o mita nt me dicati o ns 
a n d ill nesses, m ust be pr o vi de d. I n t he case of a partici pa nt deat h, a s u m mar y  of a vaila ble 
a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble t o Pfizer Safet y . 
F urt her i nf or mati o n o n f oll o w -u p pr oce d ures is pr o vi de d i n A p pe n di x 3 .
8. 4. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of an S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war d t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I RBs / ECs , a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 4. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S AE. Pers o ns at ris k f or e n vir o n me ntal 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
e x p os ure i ncl u de healt hcare pr o vi ders, fa mil y me m bers, a n d ot hers w h o ma y be e x p ose d. A n 
e n vir o n me ntal e x p os ure ma y  i ncl u de E D P, E D B , a n d occ u pati o nal e x p os ure.
A n y  s uc h ex p os ure s t o t he st u d y i nter ve nti o n u n der st u d y  are re p orta ble t o Pfizer Safet y 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
8. 4. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y  i nter ve nti o n
i nse mi nates a fe male part ner. 

A fe male n o n partici pa nt is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n 
e x p ose d t o st u d y i nter ve nti o n beca use of e n vir o n me ntal e x p os ure. Bel o w are 
e xa m ples of e n vir o n me ntal E D P :  

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n 
c o ntact.

A male fa mil y me m b er or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n c o ntact t he n i nse mi nates his fe male 
part ner pri or t o or ar o u n d t he ti me of c o nce pti o n .
T he i n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial i nf or mati o n s u b mitte d 
s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y). 

If E D P occ urs i n a partici pa nt/partici pa nt’s part ner, t he i n vesti gat or m ust re p ort t his 
i nf or mati o n t o Pfizer Safet y  usi n g t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m re gar dless of w het her a n S A E has occ urre d. Details of t he pre g na nc y will be 
c ollecte d after t he start of st u d y  i nter ve nti o n a n d 2 8 da y s after t he last d ose of st u d y 
i nter ve nti o n.

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 ng t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m . Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n 
t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he 
c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file.
F oll o w -u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 Safet y of t he o utc o me as a 
f oll o w-u p t o t he i nitial re p ort. In t he case of a li ve birt h, t he str uct ural i nte grit y  of t he ne o nate 
ca n be assesse d at t he ti me of birt h. I n t he e ve nt of a ter mi nati o n, t he reas o n(s) f or 
ter mi nati o n s h o ul d be s pecifie d a n d, if cli nically p ossi ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr oss vis ual i ns pecti o n ( u 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 co nsi dere d S A Es. If t he o utc o me of t he pre g na nc y  meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
de mise, ne o natal deat h, or c o n ge nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b 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 a s relate d or p ossi bl y relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or. F urt her 
f oll 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 ys). In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici pa nt wit h t he Pre g na nt Part ner Release of I nf or mati o n 
F or m t o deli ver t o his part ner. T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t hat 
t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his 
part ner.
8. 4. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n E D B occ urs if: 

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male n o n partici pa nt is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g 
bee n e x p ose d t o st u d y  i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of 
e n vir o n me ntal E D B is a fe male fa mily me m ber or healt hcare pr o vi der w h o re p orts 
t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y 
i n gesti o n, i n halati o n, or s ki n c o ntact. 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 create d w he n a Pfizer dr u g s pecifically a p pr o ve d f or use i n 
breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or d a nce wit h a ut h orize d use. 
H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d 
t o get her wit h t he E D B .
8. 4. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety wit hi n 2 4 
h o urs of t he i n vesti gat or’s a ware ness usi n g t he C T S A E Re p ort F or m re gar dless of w het her 
t here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure d oes n ot 
pertai n t o a partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; 
h o we ver, a c o p y of t he c o m plete d 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 o t Q u alif yi n g as AE s 
or S A Es
N ot a p plica ble.
8. 4. 8. A d verse E ve nts of S peci al I nterest
N ot a p plica ble.
8. 4. 8. 1. L ac k of Effic ac y
T his secti o n is n ot a p plica ble beca use efficac y  is n ot e x pecte d i n t he st u d y p o p ulati o n.
8. 4. 9. Me dic al De vice Deficie ncies
N ot a p plica ble.
8. 4. 1 0. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y 
i nter ve nti o n b y  t he wr o n g partici pa nt , or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Me dicati o n err ors are rec or de d a n d re p orte d as f oll o ws:
Rec or de d o n t he 
Me dic ati o n Err or P a ge 
of t he C R F
Rec or de d o n t he 
A d verse E ve nt P a ge 
of t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y  A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y  if ass ociate d wit h a n 
S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y partici pa nt .

T he a d mi nistrati o n of e x pire d st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect d osa ge;

T he a d mi nistrati o n of st u d y  i nter ve nti o n t hat has u n der g o ne te m perat ure e xc ursi o n 
fr o m t he s pecifie d st ora ge ra n ge, u nless it is deter mi ne d b y t he s p o ns or t hat t he st u d y 
i nter ve nti o n u n der q uesti o n is acce pta ble f or use.
W het her or n ot
t he me dicati o n err or is acc o m pa nie d b y a n A E, as deter mi ne d b y t he 
i n vesti gat or, suc h me dicati o n err ors occ urri n g t o a st u d y  partici pa nt are rec or de d o n t he 
me dicati o n err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge a n d, if 
a p plica ble, an 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. 6 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 5 3 5 7 8 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 ti mes ma y  c ha n ge. 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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
All ef f orts will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. 
C ollecti o n of sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are
o btai ne d wit hi n 1 0 % of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n utes of a 
6 0 - mi n ute sa m ple) will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of 
t he c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 
1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y  fro m t he n o mi nal ti me 
relati ve t o d osi n g will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he 
c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F. T his pr ot oc ol de viati o n wi n d o w 
d oes n ot a p pl y  t o sa m ples t o be c ollecte d m ore t ha n 1 0 h o urs after d ose a d mi nistrati o n at 
o ut patie nt/f oll o w -u p visits wit h visit wi n d o ws.
Sa m ples will be use d t o e val uate t he P K of P F - 0 7 8 5 3 5 7 8. Sa m ples c ollecte d f or a nalys es of 
P F -0 7 8 5 3 5 7 8 plas ma c o nce ntrati o ns ma y  als o be use d t o e val uate safety or effica c 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.
Ge netic a nal ys es will n ot be perf or me d o n t hese 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 5 3 5 7 8 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 ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi natio n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d.
Dr u g c o nce ntrati o n i nf or mati o n t hat ma y  u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gat or sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a ny pla n ne d st u d y assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
A 4 m L  bl o o d P G x sa m ple f or D N A is olati o n will be c ollecte d. D N A sa m ples will be 
a nal yz e d f or t he p ur p ose of assessi n g P N P L A 3 p ol y m or p his m (rs 7 3 8 4 0 9). As part of t his 
a nal ys is, ge n o me-wi de mar kers ma y  be use d t o c o ntr ol f or et h nic-base d ge netic ass ociati o ns.
A d diti o nall y , t hese sa m ples ma y als o be use d f or retr os pecti ve e val uati o n of a d diti o nal
ge netic varia nts ass ociate d wit h variati o n i n P K , bi o mar ker res p o nse, or t o e x pl ore A Es
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
s h o ul d t hese be o bser ve d. Sa m ples will be retai ne d f or a peri o d of u p t o 3 years after t he e n d 
of t he st u d y (e g, C S R fi nalizati o n).
I n t he e ve nt of D N A e xtracti o n fail ure, a re place me nt ge netic bl o o d sa m ple ma y be req ueste d 
fr o m t he partici pa nt.
See A p pe n di x 5 f or i nf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b ma n ual a n d ot her 
s u p p orti n g d oc u me ntati o n.
T he P G x sa m ple 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 G x pr ocessi n g
ste ps, i ncl u di n g a ny acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. O n a
case-b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple i nte grity has
bee n c o m pr o mise d. A n y sa m ple dee me d o utsi de of esta blis he d sta bilit y, or of q uesti o na ble
i nte grity, will be c o nsi dere d a pr ot oc ol de via ti o n.
As part of f urt her u n dersta n di n g t he bi ol o gical res p o nse t o st u d y  i nter ve nti o n, sa m ples ma y
be use d f or e val uati o n of ot her relate d ge n ot y pi n g as well as de vel o p me nt a n d vali dati o n of
bi oa nal y tical met h o ds.
A n y  data o utsi de of P N P L A 3 ge n ot y pi n g will be use d f or i nter nal e x pl orat or y  p ur p oses a n d 
will n ot be i ncl u de d i n t he cli nical st u d y re p ort.
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
A 4 -m L  bl o o d sa m ple o pti mize d f or D N A is olati o n Pre p D 1 will be c ollecte d acc or di n g t o 
t he S o A , as l ocal re g ulati o ns a n d IR Bs/ E C s all o w.
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n(s). 
Ge nes a n d ot her a nal y tes (e g, pr otei ns, R N A, n o n dr u g meta b olites) ma y  be st u die d usi n g t he 
retai ne d sa m ples. 
See A p pe n di x 5 f or i nf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b ma n ual a n d ot her 
s u p p orti n g d oc u me ntati o n.
8. 7. Bi o m ar kers
Bi o mar kers are n ot e val uate d i n t his st u d y .
8. 7. 1. S pecifie d Ge ne E x pressi o n ( R N A) Rese arc h 
S pecifie d ge ne e x pressi o n ( R N A) researc h is n ot i ncl u de d i n t his st u d y .
8. 7. 2. S pecifie d Pr otei n Rese arc h
S pecifie d pr otei n researc h is n ot i ncl u de d i n t his st u d y .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 7. 3. S pecifie d Me t a b ol o mic Rese arc h 
S pecifie d meta b ol o mic researc h is n ot i ncl u de d i n t his st u d y .
8. 7. 4. Ret ai ne d Rese arc h S a m ples f or Bi o m ar kers
T hese Retai ne d Researc h Sa m ples will be c ollecte d i n t his st u d y :

A 4 m L  w h ole bl o o d Pre p B 2. 5 o pti mize d f or ser u m (at eac h sa m pli n g ti me as 
o utli ne d i n t he S o A ).
Retai ne d Researc h Sa m ples will be c ollecte d as l ocal re g ulati o ns a n d I RB/ E C s all o w
acc or di n g t o t he S o A . 
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n(s). 
Ge nes a n d ot her a nal y tes (e g, pr otei ns, R N A, n o n dr u g meta b olites) ma y  be st u die d usi n g t he 
retai ne d sa m ples. 
See A p pe n di x 5 f or inf or mati o n re gar di n g ge netic researc h . Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b ma n ual a n d ot her 
s u p p orti n g d oc u me ntati o n. 
8. 8. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y .
8. 9. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n a n d h ealt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d f urt her detaile d i n t he S A P, w hic h wil l 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 h esis
N o f or mal statistical h y p ot hesis testi n g will be perf or me d i n t his st u d y .
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d 
“ E nr olle d” mea ns a partici pa nt’s, or t heir le gall y a ut h orize d 
re prese ntati ve’s, a gree me nt t o partici pate i n a cli nical st u d y 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 5
P artici p a nt A n al ysis 
Set
Descri pti o n
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
ra n d o mizati o n t o st u d y i nter ve nti o n. 
Safet y  a nalys is set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y  i nter ve nti o n. Partici pa nts will 
be a nal yz e d acc or di n g t o t he st u d y i nter ve nti o n t he y act ually 
recei ve d.
P K C o nce ntrati o n 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 recei ve at least 1 d ose of st u d y i nter ve nti o n a n d i n w h o m 
at least 1 plas ma c o nce ntrati o n val ue is re p orte d.
P K Para meter 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 recei ve at least 1 d ose of st u d y  i nter ve nti o n a n d ha ve at 
least 1 of t he P K para meters of interest calc ulate 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 perf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data. 
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal y ses of t he pri mar y a n d sec o n dar y 
a n d tertiar y/e x pl orat or y e n d p oi nts.
9. 3. 1. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n (safety a nal ysis set).
A Es, E C Gs, B P, p ulse rate, c o nti n u o us car diac m o nit ori n g, 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 dy t o e val uate t he safet y of 
partici pa nts. A n y cli nical la b orat or y, E C G, B P, p ulse rate , a n d res pirat or y rate a b n or malities 
of p ote ntial cli nical c o ncer n will be descr i be d. Safet y data will be prese nte d i n ta b ular a n d/ or 
gra p hical f or mat a n d s u m marize d descri pti vel y, w here a p pr o priate.
Me dical hist or y  a n d p h ysical e xa mi nati o n a n d ne ur ol o gical e xa mi nati o n i nf or mati o n, as 
a p plica ble, c ollecte d d uri n g t he c o urse of t he st u d y, will be c o nsi dere d s o urce data a n d will 
n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. H o we ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d d uri n g t he acti ve 
c ollecti o n peri o d will be ca pt ure d as A Es , if t h ose fi n di n gs meet t he defi niti o n of a n A E. 
Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as la b orat or y  
data, E C Gs, a n d 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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 1. 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 T i nter val, Q Tc F, P R i nter val, a n d 
Q R S c o m ple x 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 nts wit h ma xi m u m p ost- d ose Q Tc F val ues a n d ma xi m u m 
i ncreases fr o m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d b y treat me nt: 
S afet y Q Tc F Assess me nt
De gree of Pr ol o n g ati o n
Mil d ( ms)
M o der ate ( ms)
Se vere ( m s)
A bs ol ute val ue
> 4 5 0 -4 8 0
> 4 8 0 -5 0 0
> 5 0 0
I ncrease fr o m baseli ne
3 0 -6 0
> 6 0
If m ore t ha n 1 E C G is c ollecte d at a n o mi nal ti me after d ose a d mi nistrati o n (f or e xa m ple, 
tri plicate E C Gs), t he mea n of t he re plicate meas ure me nts will be use d t o re prese nt a si n gle 
o bser vati o n at t hat ti me p oi nt. I f a n y of t he 3 i n di vi d ual E C G traci n gs has a Q Tc F val ue 
> 5 0 0 ms, b ut t he mea n of t he tri plicates is n ot > 5 0 0 ms, t he data fr o m t he partici pa nt’s 
i n di vi d ual traci n g will be descri be d i n a safety secti o n of t he C S R i n or der t o place t he > 5 0 0
ms val ue i n a p pr o priate cli nical c o nte xt. H o we ver, val ues fr o m i n di vi d ual traci n gs wit hi n 
tri plicate meas ure me nts t hat are > 5 0 0 ms will n ot be i ncl u de d i n t he cate g orical a nal ys is 
u nless t he a vera ge fr o m t he tri plicate meas ure me nts is als o > 5 0 0 ms. C ha n ges fr o m baseli ne 
will be defi ne d as t he c ha n ge bet wee n t he p ost d ose Q Tc F val ue a n d t he a vera ge of t he pre -
d ose tri plicate val ues at - 1, - 0. 5, a n d 0 h o urs pre-d ose o n Da y  1.
I n a d diti o n, a n atte m pt will be ma de t o e x pl ore a n d c haracterize t he relati o ns hi p bet wee n 
plas ma c o nce ntrati o n a n d Q T i nter val le n gt h usi n g a P K/ P D m o deli n g a p pr oac h. If a P K/ P D 
relati o ns hi p is f o u n d, t he i m pact of partici pa nt fact ors (c o variates) o n t he relati o ns hip will be 
e xa mi ne d. T he res ults of s uc h a nal ys es ma y n ot be i ncl u de d i n t he C S R.
9. 3. 2. P K E n d p oi nts
T he P K c o nce ntrati o n a n d para meter p o p ulati o ns are d efi ne d i n Secti o n 9. 2 .
9. 3. 2. 1. Deri v ati o n of P F - 0 7 8 5 3 5 7 8 P K P ar a meters
T he plas ma P K para meters f or P F - 0 7 8 5 3 5 7 8, f oll o wi n g oral d ose a d mi nistrati o n, will be 
deri ve d fr o m t he plas ma c o nce ntrati o n- ti me pr ofiles usi n g sta n dar d n o nc o m part me ntal 
met h o ds as detaile d i n Ta ble 4 , as data per mit. 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. If 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 mes will be use d i n t he deri vat i o n of P K para meters.
T a ble 4 .
Pl as m a P F - 0 7 8 5 3 5 7 8 P K P ar a meters
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 last
Area u n der t he plas ma
c o nce ntrati o n-ti me pr ofile fr o m
ti me 0 t o t he ti me of t he last
q ua ntifia ble c o nce ntrati o n ( C last)
Li near/ L o g tra pez oi dal met h o d
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 4 .
Pl as m a P F - 0 7 8 5 3 5 7 8 P K P ar a meters
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 plas ma
c o nce ntrati o n-ti me pr ofile fr o m
ti me 0 e xtra p olate d t o i nfi nite ti me
A U C last + ( C last*/ k el), w here Clast* is t he pre dicte d 
plas ma c o nce ntrati o n at t he last q ua ntifia ble 
ti me p oi nt esti mate d fr o m t he l o g-li near 
re gressi o n a nal ysis
C ma x
Ma xi m u m plas ma c o nce ntrati o n
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 eli mi nati o n 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 g-li near c o nce ntrati o n-ti me c ur ve. O nl y t h ose 
data p oi nts j u d ge d t o descri be t he ter mi nal l o g -
li near decli ne will be use d i n t he re gressi o n.
C L/ 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)
A U C last( d n)
D ose -n or m alize d A U C last
A U C last/ D ose
A U C i nf( d n) *
D ose -n or m alize d A U C i nf
A U C i nf/ D ose
C ma x ( d n)
D ose -n or m alize d C ma x
C ma x / D ose
* As data per mits .
9. 3. 2. 2. St atistic al Met h o ds f or P K D at a
Plas ma c o nce ntrati o ns of P F- 0 7 8 5 3 5 7 8 will be liste d a n d s u m marize d descri pti vel y  b y d ose 
(a n d fasti n g c o n diti o n a n d f or m ulati o n , if a p pr o priate) a n d n o mi nal P K sa m pli n g ti me. 
I n di vi d ual partici pa nt 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  d ose (a n d fasti n g c o n diti o n a n d f or m ulati o n , if a p pr o priate) usi n g act ual (f or 
i n di vi d ual) a n d n o mi nal (f or me dia n) ti mes res pecti vel y. Me dia n pr ofiles will be prese nte d 
o n b ot h li near a n d l o g scales.
T he plas ma P K para meters will be s u m marize d descri pti vel y  b y d ose (a n d fasti n g c o n diti o n
a n d f or m ulati o n, if a p pr o priate) as a p plica ble. D ose-n or malize d A U C i nf, A UC last, a n d C ma x
will be pl otte d a gai nst d ose (a n d fasti n g c o n diti o n a n d f or m ulati o n, if a p pr o priate) usi n g b o x-
a n d-w his ker p lots , a n d will i ncl u de i n di vi d ual partici pa nt val ues a n d t he ge o metric mea ns f or 
eac h d ose. T hese pl ots will be use d t o u n dersta n d t he relati o ns hi p bet wee n t he P K para meters 
a n d d ose (a n d fasti n g c o n diti o n a n d f or m ulati o n, if a p pr o priate).
If t he f o o d effect is assesse d, a mi xe d effects A N O V A will be perf or me d se paratel y  o n t he 
nat ural l o g tra nsf or me d A U C i nf, A UC last, a n d C ma x ( d ose-n or malize d pri or t o a nal y sis, if 
a p pr o priate) wit h fasti n g c o n diti o n i ncl u de d as a fi xe d effect a n d partici pa nt as a ra n d o m 
effect. F urt her details of t his a nal ysis will be pr o vi de d i n t he S A P.
If t he I D S oral s ol uti o n is assesse d, a mi xe d effects A N O V A will be perf or me d se parately o n 
t he nat ural l o g tra nsf or me d A U C i nf, A UC last, a n d C ma x ( d ose-n or malize d pri or t o a nal y sis, if 
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 p pr o priate) wit h f or m ulati o n i ncl u de d as a fi xe d effect a n d partici pa nt as a ra n d o m effect. 
F urt her details of t his a nal y sis will be pr o vi de d i n t he S A P.
A d diti o nal P K a nal y ses ma y be perf or me d if dee me d a p pr o priate a n d ma y n ot be i ncl u de d i n 
t he C S R.
9. 3. 3. Ter ti ar y/ E x pl or at or y E n d p oi nt(s) A n al ysis
T he a nal ys is of tertiar y/e x pl orat or y e n d p oi nts will be detaile d i n t he S A P.
9. 3. 4. Ot her A n al yses 
P G x 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 naly ses; t he res ults of s uc h a nalys 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. 
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  2 4 healt h y a d ult partici pa nts ( u p t o 3 c o h orts of 
a p pr o xi matel y 8 partici pa nts eac h) has bee n c h ose n base d o n t he nee d t o mi ni mize first 
e x p os ure t o h u ma ns of a ne w c he mical e ntit y  a n d t he re q uire me nt t o pr o vi de a de q uate safety, 
t olera bilit y, a n d P K assess me nt at eac h d ose le vel. At eac h d ose le vel, a p pr o xi matel y
6 partici pa nts are pla n ne d t o recei ve P F- 0 7 8 5 3 5 7 8 a n d a p pr o xi matel y 2 partici pa nts are 
pla n ne d t o recei ve place b o wit h all partici pa nts at t he e n d of t he st u d y ha vi n g recei ve d u p t o 
4 d oses of P F -0 7 8 5 3 5 7 8 a n d u p t o 2 d oses of place b o.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nt s a gai nst a ny i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes that t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. Fi n a nci al Discl os ure
N ot a p plica ble.
1 0. 1. 3. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or t he i n vesti gat or’s re prese ntati ve will e x plai n t he nat ure of t he st u d y, 
i ncl u di n g t he ris ks 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 ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt ’s 
pers o n al data. 
T he partici pa nt m ust be i nf or me d t hat t heir pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.
T he i n v esti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt is f ull y i nf or me d a b o ut t heir
ri g ht t o access a n d c orrect t heir pers o nal data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of 
t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o s i g n t he I CD.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I R B/ E C-a p pr o ve d I CD (s) 
d uri n g t heir partici pati o n i n t he st u d y as re q uire d per l ocal re g ulati o ns.
A c o p y of t he I C D (s) m ust be pr o vi de d t o t he partici pa nt.
Partici pa nts w h o ar e rescree ne d are re q uire d t o si g n a ne w I C D.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

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

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 4
1 0. 1. 8. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nts are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e 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 h ts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 9. Use of Me dic al Rec or ds
I n certai n sit uati o ns, s p o ns or re vie w of re dacte d c o pies of partici pa nt me dical rec or ds f or 
treat me nt of a n A E m a y  be perf or me d, 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 safety. 
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 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T here ma y  be u n plan 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. 1 0. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or , i ncl u di n g ( b ut n ot li mite d t o) 
re g ulat or y a ut h ority decisi o n, c ha n ge i n o pi ni o n of t he I R B/ E C, or c ha n ge i n be nefit -ris k 
assess me nt . St u d y  sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d 
cl ose d w he n all re q uire d d oc u me nts a n d st u d y  s u p plies ha ve bee n c ollecte d a n d a st u 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 if 
re q ueste d t o d o s o by t he res p o nsi ble I R B/ E C or if s uc h ter mi nati o n is re q uire d t o pr otect t he 
healt h of st u d y  partici pa nts.
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or’s pr oce d ures, or t he I CH G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf o r m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 1 1. P u blic ati o n P olic y
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns. 
Pfizer will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he i n vesti gat or’s partici pati o n i n t he 
pre parati o n of t he pri mar y c o n gress a bstract, p oster , prese ntati o n, or pri mar y ma n uscri pt f or 
t he st u d y.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 7
1 0. 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. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nical la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y iss ues.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 8
T a ble 5 .
Pr ot oc ol -Re q uire d L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
H e m o gl o bi n
H e m at ocrit
R B C c o u nt
M C V, M C H, M C H C
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils ( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
Urea
Creati ni ne
C ystati n C a
e G F R b
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T , G G T
T bili
Direct a n d i n direct bilir u bi n c
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
Li pi d pa nel:
T otal c h olester ol
Tri gl yceri des
H D L
L D L ( direct)
L ocal d i pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y a n d 
cult ure d
Uri n e dr u g scree ni n gf
At scree ni n g o nl y:

F S H e

H Bc A b

H Bs A b g

H Bs A g

H C V A b

HI V

Uri ne he me h

Uri ne 
al b u mi n -t o-creati ni ne 
rati o ( q ua ntitati ve)i
C O VI D -1 9 testi n g ( per 
C R U pr oce d ures)
If H b/ R B C a b n or mal:
Ne utr o p hils ( %)
E osi n o p hils ( %)
Bas o p hils ( %)
L y m p h oc ytes ( %)
M o n oc ytes ( %)
R B C m or p h ol o g y
R B C distri b uti o n wi dt h
Re q uire d :
F or s us pecte d DI LI:
A S T/ A L T 
T bili, al b u mi n, C K, direct 
a n d i n direct bili r u bi n
G G T, P T/I N R, e osi n o p hils 
( %), al kali ne p h os p hatase
T he f oll o w i n g a d diti o nal 
testi n g ma y be warra nte d: 
Aceta mi n o p he n/ paraceta m ol 
or pr otei n a d d uct le vels 
He patitis ser ol o g y (e ve n if 
scree ni n g ne gati ve) 
T otal bile aci ds
Li ver i ma gi n g
F or s us pecte d DI CI/ DI KI: 
Creati ni ne ( Screat) 
C ystati n C a ( Sc ys) 
e G F R ( Screat o nl y a n d 
c o m bi ne d Screat + Sc ys)
S p ot ( di pstic k) U A C R
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 5 .
Pr ot oc ol -Re q uire d L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
a.
C ystati n C ( Sc ys):  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 Screat 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 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. 7. 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.
Test as refle x if T bili is ele vate d.
d.  
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.
e.
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.
f.
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 ocai ne, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot hers are site - a n d st u d y-s pecific).
g.
Test as refle x if H Bs A g a n d/ or H Bc A b are p ositi ve.
h.
Assesse d b y uri ne di pstic k.
i.
Assesse d b y uri ne di pstic k or uri ne sa m ple bi oc he mical a nal ysis.
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.
La b orat or y /a nalyt e res ults t hat c o ul d u n bli n d t he st u d y  a n d ha ve bee n c ollecte d f or t he 
p ur p ose of t he st u d y will n ot be re p orte d t o i n vesti gat or sites or ot her bli n de d pers o n nel u ntil 
t he st u d y has bee n u n bli n de d.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical 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 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

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

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

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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 o f t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0 . 1.9 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n 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.

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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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 dedicate d secti o n of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
F oll o w - Up of A E s a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of 
s u p ple me ntal meas ure me nts a n d/ or e val uati o ns, as me dicall y i n dicate d or as 
re q ueste d by t he s p o ns or, t o el uci date t he nat ure a n d/ or ca usality of t he A E or 
S A E as f ull y  as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt hcare pr o vi ders .

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs , i ncl u di n g hist o pat h ol o g y.

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 .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 
h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A E s
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D C T

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic D C T (e g, e S A E or P S S A) .

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E re p ort 
f or m (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic D C T (e g, e S A E or P S S A) or 
pa per f or m (as a p plica ble) as s o o n as t he data bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic D C T will be ta ke n 
off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves 
u p date d data o n a pre vi o usl y  re p orte d S A E after t he electr o nic D C T has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a t he C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort 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 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 7
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 da ys after t he last d ose of stu d y  i nter ve nti o n, w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safet y ris k of t he st u d y  
i nter ve nti o n(s): 

Refrai n fr o m d o nati n g s per m.
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse as t heir preferre d a n d us ual lifest y le 
(a bsti nent o n a l o n g -ter m a n d persiste nt basis) a n d a gree t o re mai n a bsti ne nt. 
O R

M ust a gree t o use c o ntrace pti o n/ barrier as detaile d bel o w:

A gree t o use a male c o n d o m , a n d s h o ul d als o be a d vise d of t he be nefit f or a 
fe male part ner t o use a hi g hly effecti ve met h o d of c o ntrace pti o n, as a c o n d o m 
ma y  brea k or lea k, w he n ha vi n g se x ual i nterc o urse wit h a W O C B P w h o is n ot 
c urre ntl y pre g na nt.

I n a d diti o n t o male c o n d o m use, a hi g hly effecti ve met h o d of c o ntrace pti o n is 
rec o m me n de d i n W O C B P part ners of male partici pa nts (refer t o t he list of hi g hl y 
effecti ve met h o ds bel o w i n Secti o n 1 0. 4. 4 ).
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Crite ri 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 Sect i o n 1 0. 4. 4 f or a 
c o m plete list of c o ntrace pti ve met h o ds per mitte d i n t he st u d y . 
A fe male partici pa nt is eli gi ble t o partici pate if s he (a) is n ot pre g na nt or breastfee di n g; a n d 
( b) a grees n ot t o d o nate e g gs ( o va, o oc ytes) f or t he p ur p ose of re pr o d ucti o n for 2 8 da y s; a n d 
(c) is n ot a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n earl y u n detecte d 
pre g na nc y . 
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
If fertilit y is u nclear (e g, a me n orr hea or oli g o me n o rr 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 y sterect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a me dical ca use ot her t ha n t he a b o ve
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site pers o n nel’s 
re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y 
i nter vie w. T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he partici pa nt’s me dical 
rec or d f or t he st u dy.
2.
P ost me n o pa usal fe male .

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A h i g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars ol d a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A f e male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt m ust disc o nti n ue 
H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  e nr oll me nt.
1 0. 4. 4. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat H a ve L o w User De pe n de nc y (f or W O C B P part ners of male 
partici pa nts)
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.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 9
2.
I ntra uteri ne de vice.
3.
I ntra uteri ne h or m o ne-releasi n g s yste m.
4.
Bilateral t u bal occl usi o n.
5.
Vasect o mize d part ner.

Vasect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he W O C B P a n d t he a bse nce of s per m has 
bee n c o nfir me d. If n ot, a n a d diti o nal hi g hl y effecti ve met h o d of c o ntrace pti o n 
s h o ul d be use d. T he s per mat o ge nesis c ycle is a p pr o xi matel y 9 0 da ys.
Hi g hl y Effecti ve Met h o ds T hat A re User D e pe n de nt (f or W O C B P part ners of male 
partici pa nts)
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 nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral + b arrier *

I njecta ble + b arrier *
8.
Se x ual A bsti ne nce
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual lifestyl e of t he 
partici pa nt .
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o ns 6 or 7 f or t he st u dy 
i ncl u de a ny of t he f oll o wi n g:

Male or fe male c o n d o m wit h or wit h o ut s per mic i de;

Cer vical ca p, dia p hra g m , or s p o n ge wit h s per mici de;
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

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

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

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 4
f or m ulae (see Secti o n 1 0. 7. 2 ) a n d ca n use rec o m me n de d o nli ne ki d ne y  f u ncti o n calc ulat ors 
t o re d uce t he li keli h o o d of a calc ulati o n err or. 
T he U S Nati o nal Ki d ne y  F o u n dati o n O nli ne Calc ulat ors. 

A d u lts ( 1 8 years a n d a b o ve) - 2 0 2 1 C K D -E PI  Creati ni ne O nli ne Calc ulat or (e G F R): 
htt ps:// w w w. ki d ne y . or g/ pr ofessi o nals/ K D O QI/ gfr _calc ulat or
I n vesti gati o nal sites are res p o nsi ble t o e ns ure t hat t he acc urate a ge-s pecific e q uati o n is 
selecte d a n d t hat t he c orrect u nits f or ser u m creati ni ne ( m g/ d L o nly), S c y s ( m g/ L o nly), t otal 
b o d y  wei g ht ( k g o nl y), a n d a ge ( years). I n vesti gat ors are e x pecte d t o (i) re vie w a n d c o nfir m 
c orrect ness of t he ki d ne y f u ncti o n calc ulati o n res ults a n d (ii) e val uate t he calc ulate d val ue 
wit hi n t he c o nte xt of hist orical i nf or mati o n a vaila ble t o t he m i n t he partici pa nt’s me dical 
rec or d. I n vesti gat ors are res p o nsi ble f or t he cli nical o versi g ht of t he partici pa nt eli gi bilit y 
pr ocess, ki d ne y  f u ncti o n calc ulati o n, a n d d ose selecti o n a n d a dj ust me nts per st u d y pr ot oc ol. 
I n vesti gat ors are e nc o ura ge d t o direct q uesti o ns or u ncertai nties re gar di n g ki d ne y f u ncti o n 
a n d d osi n g t o t he Pfiz er Cli nical Tea m a n d Me dical M o nit or, if nee de d.
1 0. 7. 4. A d verse E ve nt Gr a di n g f or Ki d ne y S afet y L a b or at or y A b n or m alities
A E gra di n g f or decli ne i n ki d ne y f u ncti o n (ie, e G F R or e Cr Cl) will be acc or di n g t o Ki d ne y  
Disease: I m pr o vi n g Gl o bal O utc o mes ( K DI G O) criteria f or b ot h pe diatric a n d a d ult 
partici pa nts .
K DI G O 
criteria
Gra de 1  
Gra de 2  
Gra de 3  
Gra de 4  
Gra de 5
Decrease 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 
e G F R ≥9 0 
m L/ mi n/ 1. 7 3 m² 
O R                
e Cr Cl ≥9 0 
m L/ mi n 
e G F R ≥6 0 t o 8 9 
m L/ mi n/ 1. 7 3 m² 
O R                
e Cr Cl ≥6 0 t o 8 9 
m L/ mi n 
e G F R 3 0 t o 5 9 
m L/ mi n/ 1. 7 3 m² 
O R e Cr Cl 3 0 t o 
5 9 m L/ mi n
e G F R 1 5 t o 2 9 
m L/ mi n/ 1. 7 3 m² 
O R e Cr Cl 1 5 t o 
2 9 m L/ mi n
e G F R < 1 5 
m L/ mi n/ 1. 7 3 m² O R 
e Cr Cl < 1 5 m L/ mi n 
O R dial ysis i n dicate d
Al b u mi n uria
Al b u mi n uria < 3 0 
m g/ g O R < 3 
m g/ m m ol
Al b u mi n uria     
3 0 t o 3 0 0 m g/ g 
O R 3 t o 3 0 
m g/ m m ol
Al b u mi n uria 
> 3 0 0 m g/ g m O R 
< 3 m g/ m m ol
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

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

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 6

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 ura ti o n wit h rele va nt sy m pt o ms or lasti n g > 1 mi n ute) .

Ve ntric ular r h y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (H R
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m [s uc h as
torsa des de p oi ntes ]).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d- de gree) h eart b l oc k.
E C G 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 nvesti gat or a n d Pfizer st u d y tea m , a n d n ot t o be c o nsi dere d as all-
i ncl usi ve of w hat is t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 7
1 0. 9. A p pe n di x 9: Pr o hi bite d C o nc o mit a nt Me dic ati o ns T h at M a y Res ult i n D DI 
P F -0 7 8 5 3 5 7 8 is pri maril y meta b olize d b y 
. T heref ore, as o utli ne d i n Secti o n 5. 2 a n d 
Secti o n 6. 9 , 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 
t hat are mo derate or str o n g 
 i n d ucers or i n hi bit ors 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. 
A n o n -e x ha usti ve list of e xcl u de d m o derate or str o n g  
 i n d ucers or i n hi bit ors is bel o w.
Beca use t his is n ot a n all -i ncl usi ve list, site staff s h o ul d c o ns ult wit h t he s p o ns or or desi g nee 
wit h a n y  q uesti o ns re gar di n g p ote ntial D DI. T he Pfizer st u d y  tea m is t o be n otifie d of a n y 
pr o hi bite d me dicati o ns ta ke n d uri n g t he st u d y.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 8
T his list of dr u gs pr o hi bite d f or p ote ntial D DI  c o ncer ns ma y be re vise d d uri n g t he c o urse of 
t he st u d y wit h writte n n otificati o n fr o m s p o ns or, t o i ncl u de or e xcl u de s pecific dr u gs or dr u g 
cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or t he I M P, a vaila bilit y  of ne w 
i nf or mati o n i n literature o n t he D DI p ote ntial of ot her dr u gs) , if t he o verall be nefit:ris k 
assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y i m pact t he safet y of 
partici pa nts or t he scie ntific val ue of t he trial .
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 9
1 0. 1 0. A p pe n di x 1 0 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Ter m
A bs
a bs ol ute
A D L
acti vit y/acti vities of daily li vi n g
A E
a d verse e ve nt
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A N O V A
A nal y sis of Varia nce
A S O
antise nse oli g o n ucle oti des
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
A U C 2 4
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4 
h o urs
A U C i nf
area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m ti me 0 
e xtra p olate d t o i nfi nite ti me
A U C i nf(d n )
D ose -n or malize d A U C i nf
A U C last
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o t he 
ti me of t he last q ua ntifia ble c o nce ntrati o n
A U C last(d n )
D ose -n or malize d A U C last
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
B A C -T G
bacterial artificial c hr o m os o me tra ns ge ne
B B S
Bi os peci me n Ba n ki n g S yste m
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
C a v
avera ge plas ma c o nce ntrati o n
C D P
Cli nical De vel o p me nt Pla n
C eff
efficaci o us c o nce ntrati o n
C F R
C o de of Fe deral Re g ulati o ns
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 last
last q ua ntifia ble c o nce ntrati o n
C L / F
a p pare nt oral cleara nce
C L p
p las ma cleara nce
C ma x
ma xi m u m plas ma c o nce ntrati o n
C ma x (d n )
D ose -n or malize d C ma x
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 0
A b bre vi ati o n
Ter m
C N S
ce ntral ner v o us s ys te m
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
Cr
creati ni ne
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C R U
cli nical researc h u nit
C S R
Cli nical St u d y  Re p ort
C T
cli nical trial
C TI S
Cli nical Trial I nf or mati o n S y ste m
C Y P
c yt oc hr o me P 4 5 0
C Y P 3 A
c yt oc hr o me P 4 5 0 3A
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 n
d ose -n or malize d
D N A
d e o x yri b o n ucleic aci d
E C
et hics c o m mittee
E C C
e mer ge nc y c o ntact car d
E C G
electr ocar di o gra m or electr ocar di o gra p h y
e Cr Cl
esti mate d creati ni ne cleara nce
e C R F
electr o nic case re p ort f or m
E D B
e x p os ure d uri n g breastfee di n g
E -D M C
E xter nal Data M o nit ori n g C o m mittee
E D P
e x p os ure d uri n g pre g na nc y
E D R
e xte m p ora ne o us dis pe nsi n g rec or d
e G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
e S A E
electr o nic seri o us a d verse e ve nt
E 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
F o o d a n d Dr u g A d mi nistrati o n
FI H
first-i n-h u ma n
F S H
f ollicle-sti m ulati n g h or m o ne
G C P
G o o d Cli nical Practice
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
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 1
A b bre vi ati o n
Ter m
H b
he m o gl o bi n
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 C
he pat ocell ular carci n o ma
H C V A b
he patitis C a nti b o d y
H D L
hi g h -de nsit y li p o pr otei n
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
I n vesti gat or’s Br oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use
I D
i de ntificati o n
I D S
i nter me diate d osa ge stre n gt h
Ima x
ma xi m u m i n hi bit or y effect
I M P
i n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal Ne w Dr u g 
I N R
i nter nati o nal n or malize d rati o
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I P M
i n vesti gati o nal pr o d uct ma n ual
I Q M P
i nte grate d q uality ma na ge me nt pla n
I RB
I nstit uti o nal Re vie w B oar d
I V
intra ve n o us(l y)
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
eli mi nati o n rate c o nsta nt
L B B B
left b u n dle bra nc h bl oc k
L D L
l o w-de nsit y  li p o pr otei n
L F T
li ver f u ncti o n test
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 QI
me dicall y  q ualifie d i n di vi d ual
N A
n ot a p plica ble
N A F L D
n o nalc o h olic fatt y li ver disease
N A S H
n o nalc o h olic steat o he patitis
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o -o bser ve d -a d verse-effect le vel
N O E L
n o -o bser ve d -effect le vel
P C R U
Pfizer Cli nical Researc h U nit
P D
p har mac o d y n a mic(s)
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 2
A b bre vi ati o n
Ter m
P E
p h y sical e xa mi nati o n
P G x
p har mac o ge n o mic
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic(s)
P N P L A 3
Patati n -li ke p h os p h oli pase d o mai n-c o ntai ni n g pr otei n 3
P N P L A 3 - 1 4 8 M 
is ole uci ne t o met hi o ni ne s u bstit uti o n at a mi n o aci d p ositi o n 1 4 8 of
t he P N P LA 3 pr otei n
P N P L A 3 -W T
wil dt y pe P N P L A 3
P R O T A C
pr ote ol y sis tar geti n g c hi mera
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 D
o nce dail y
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
Scr eat
ser u m creati ni ne
Sc y s
ser u m c ystati n C
s h R N A
s mall hair pi n R N A
S o A
S c he d ule of A cti vities
S O P
sta n dar d o perati n g pr oce d ure
S R S D
Si n gle Refere nce Safet y D oc u me nt
S U S A R
sus pecte d u ne x pecte d seri o us ad verse reacti o n
t½
ter mi nal eli mi nati o n half-life
T B D
t o be deter mi ne d
T bili
t otal bilir u bi n
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me f or Cma x
U A
uri ne al b u mi n
U A C R
uri ne al b u mi n/creati ni ne rati o
U G T
U D P -gl uc ur o n os yl tra nsferase
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
V ss
v ol u me of distri b uti o n at stea d y  state
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)
C CI
C CI
C CI

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 3
A b bre vi ati o n
Ter m
V z/ F
a p pare nt oral v ol u me of distri b uti o n
W B C
w hite bl o o d cell
W O C B P
w o ma n/ w o me n of c hil d beari n g p ote ntial
W T
wil d -t ype
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 4
1 1. R E F E R E N C E S
1.
Re vie w T, La Brec q ue D R, A b bas Z, et al. W orl d Gastr oe nter ol o g y  Or ga nisati o n 
gl o bal g ui deli nes: N o nalc o h olic fatt y li ver disease a n d n o nalc o h olic steat o he patitis. J Cli n 
Gastr oe nter ol. 2 0 1 4; 4 8( 6): 4 6 7 - 7 3.
2.
Y o u n ossi Z M, K oe ni g A B, A b delatif D, et al. Gl o bal e pi de mi ol o g y  of n o nalc o h olic 
fatt y li ver disease-Meta -a nal ytic assess me nt of pre vale nce, i nci de nce, a n d o utc o mes. 
He pat ol o g y . 2 0 1 6; 6 4( 1): 7 3- 8 4.
3.
Die hl A M, Da y  C. Ca use, Pat h o ge nesis, a n d Treat me nt of N o nalc o h olic 
Steat o he patitis. N E n gl J Me d. 2 0 1 7; 3 7 7( 2 1): 2 0 6 3- 7 2.
4.  
K ha n F Z, Per u m pail R B, W o n g RJ, et al. A d va nces i n he pat ocell ular carci n o ma: 
N o nalc o h olic steat o he patitis -relate d he pat ocell ular carci n o ma. W orl d J He pat ol. 
2 0 1 5; 7( 1 8): 2 1 5 5 - 6 1.
5.
R o me o S, K ozliti na J, Xi n g C, et al. Ge netic variati o n i n P N P L A 3 c o nfers 
s usce pti bilit y t o n o nalc o h olic fatt y li ver disease. Nat Ge net. 2 0 0 8; 4 0( 1 2): 1 4 6 1- 5.
6.  
Ge n o me A g gre gati o n Data base ( g n o m A D) v 3. 1. 2 [ A vaila ble fr o m: 
htt ps://re gistr y . o pe n data.a ws/ br oa d-g n o ma d/ ].
7.
Karcze ws ki KJ, Fra nci oli L C, Tia o G, et al. T he m utati o nal c o nstrai nt s pectr u m 
q ua ntifie d fr o m variati o n i n 1 4 1, 4 5 6 h u ma ns. Nat ure. 2 0 2 0; 5 8 1( 7 8 0 9): 4 3 4 - 4 3.
8.
Gri ma u d o S, Pi pit o ne R M, Pe n nisi G, et al. Ass oci ati o n Bet wee n P N P L A 3 rs 7 3 8 4 0 9 
C > G Varia nt a n d L i ver-Relate d O utc o mes i n Patie nts Wit h N o nalc o h olic Fatt y Li ver 
Disease. Cli n Gastr oe nter ol He pat ol. 2 0 2 0; 1 8( 4): 9 3 5- 4 4 e 3.
9.  
H ol mer M, E kste dt M, Nasr P, et al. Effect of c o m m o n ge netic varia nts o n t he ris k o f 
cirr h osis i n n o n -alc o h olic fatt y li ver disease d uri n g 2 0 years of f oll o w-u p. Li ver I nt. 
2 0 2 2; 4 2( 1 2): 2 7 6 9 - 8 0.
1 0.
Li u Y L, Pat ma n G L, Leat hart J B, et al. Carria ge of t he P N P L A 3 rs 7 3 8 4 0 9 C > G 
p ol y m or p his m c o nfers a n i ncrease d ris k of n o n- alc o h olic fatt y li ver disease ass ociate d 
he pat ocell ular carci n o ma. J He pat ol. 2 0 1 4; 6 1( 1): 7 5 - 8 1.
1 1.
U nal p -Ari da A, R u hl C E. Patati n -Li ke P h os p h oli pase D o mai n -C o ntai ni n g Pr otei n 3 
I 1 4 8 M a n d Li ver Fat a n d Fi br osis Sc ores Pre dict Li ver Disease M ortalit y i n t he U. S. 
P o p ulati o n. He pat ol o g y . 2 0 2 0; 7 1( 3): 8 2 0- 3 4.
1 2.
Dai G, L i u P, Li X, et al. Ass ociati o n bet wee n P N P LA 3 rs 7 3 8 4 0 9 p ol y m or p his m a n d 
n o nalc o h olic fatt y li ver disease ( N A F L D) s usce pti bilit y  a n d se verit y: A meta-a nal ys is. 
Me dici ne ( Balti m ore). 2 0 1 9; 9 8( 7):e 1 4 3 2 4.
1 3.
Bas u Ra y  S, S ma gris E, C o he n J C, et al. T he P N P L A 3 varia nt ass ociate d wit h fatt y 
li ver disease (I 1 4 8 M) acc u m ulates o n li pi d dr o plets b y e va di n g u bi q uit ylati o n. He pat ol o g y. 
2 0 1 7; 6 6( 4): 1 1 1 1 - 2 4.
1 4.
Bas u Ra y  S, Wa n g Y, S ma gris E, et al. Acc u m ulati o n of P N P L A 3 o n li pi d dr o plets is 
t he basis of ass ociate d he patic steat osis. Pr oc Natl Aca d Sci U S A. 2 0 1 9; 1 1 6( 1 9): 9 5 2 1- 6.
1 5. 
Li n de n D, A h n mar k A, Pi n git ore P, et al. P n pla 3 sile nci n g wit h a ntise nse 
oli g o n ucle oti des a meli orates n o nalc o h olic steat o he patitis a n d fi br osis i n P n pl a 3 I1 4 8 M 
k n oc k -i n mice. M ol Meta b. 2 0 1 9; 2 2: 4 9- 6 1.
1 6.
I n Vitr o Dr u g I nteracti o n St u dies —
C y t oc hr o me P 4 5 0 E nz yme - a n d Tra ns p orter -
Me diate d Dr u g I nteracti o ns G ui da nce f or I n d ustr y: U. S. F o o d & Dr u g A d mi nistrati o n; 2 0 2 0 
[ A vaila ble fr o m: htt ps:// w w w.f da. g o v/r e g ulat or y-i nf or mati o n/searc h-f da-g ui da nce -
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)

P F -0 7 8 5 3 5 7 8
Pr ot oc ol C 5 1 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 1 , 0 6 J u ne 2 0 2 3 
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 5
d oc u me nts/i n -vitr o -dr u g -i nteracti o n-st u dies-c yt oc hr o me- p 4 5 0-e nz yme -a n d -tra ns p orter-
me diate d -dr u g -i nteracti o ns].
1 7.
G ui deli ne o n t he i n vesti gati o n of dr u g i nteracti o ns: E ur o pea n Me dici nes A ge nc y ; 
2 0 1 3 [ A vaila ble fr o m: htt ps:// w w w.e ma.e ur o pa.e u/e n/ d oc u me nts/scie ntific-
g ui deli ne/ g ui deli ne -i n vesti gati o n-dr u g -i nteracti o ns-re visi o n-1 _e n. p df ].
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 M e d. 2 0 2 1; 3 8 5( 1 9): 1 7 3 7 - 4 9.
0 9 0 1 7 7 e 1 9 d a 8 a 2 5 1\ A p pr o v e d\ A p pr o v e d O n: 0 6- J u n- 2 0 2 3 1 7: 2 8 ( G M T)