Clinical trial NCT05890105
Conditions: Healthy Participants
Sponsor: Pfizer
Start date: 2023-06-02; Completion date: 2023-12-01
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purposes of this study are:

* To see how the new medicine (PF-07853578) under study is tolerated. And if there are any important side effects. And, how people feel after taking single increasing amount of the medicine by mouth.
* To measure the amount of study medicine in your blood after the medicine is taken by mouth.

This study is seeking for participants who:

* are females of 18 to 65 years old and are not able to give birth to a child.
* are males of 18 to 65 years old.
* have body mass index of 16 to 31 kilograms per meter squared.
* have a total body weight of more than 50 kilograms (110 pounds). Participants will be randomly selected to receive either study medicine (PF-07853578) or placebo (a pill that has no medicine in it). Participants may receive up to 4 amounts of study medicine and up to 2 amounts of placebo.

Detailed description:

Arms: arm 1: Single dose administration of PF-07853578 and placebo. Participants will receive up to 4 dose levels of PF-07853578 and up to 2 dose levels of matching placebo. arm 2: Single dose administration of PF-07853578 and placebo. Participants will receive up to 4 dose levels of PF-07853578 and up to 2 dose levels of matching placebo. arm 3: Single dose administration of PF-07853578 and placebo. Participants will receive up to 4 dose levels of PF-07853578 and up to 2 dose levels of matching placebo.
Interventions: intervention 1: PF-07853578 intervention 2: Placebo
Intervention descriptions: intervention 1: PF-07853578 will be administered as oral solutions or suspensions as escalating single doses to be determined. intervention 2: Placebo will be administered as oral solutions or suspensions as escalating single doses to be determined.

Protocol documents:
Prot_000.pdf: 
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)

SAP_001.pdf: 
Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 1 of 26
Protocol C5161001
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
Statistical Analysis Plan 
(SAP)
Version:
1
Date:
23 Jun 2023
090177e19e109681\Approved\Approved On: 18-Jul-2023 14:34 (GMT)


Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 2 of 26
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Modifications to the Analysis Plan Described in the Protocol..................................5
2.2. Study Objectives, Endpoints, and Estimands............................................................5
2.3. Study Design .............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7
3.1. Primary Endpoint(s) ..................................................................................................7
3.1.1. Adverse Events.............................................................................................8
3.1.2. Laboratory Data............................................................................................8
3.1.3. Vital Signs ....................................................................................................8
3.1.4. Electrocardiograms.......................................................................................9
3.1.5. Continuous Cardiac Monitoring ...................................................................9
3.1.6. Neurological examinations.........................................................................10
3.1.7. Physical Examinations................................................................................10
3.2. Secondary Endpoint(s) ............................................................................................10
3.3. Other Endpoint(s)....................................................................................................11
3.3.1. Additional Plasma PF-07853578 PK Parameters.......................................11
3.3.2. Plasma PF-07853578 PK Parameters During Food Effect Period (if 
conducted)........................................................................................................11
3.3.3. Plasma PF-07853578 PK Parameters During IDS Oral Solution 
Period (if conducted)........................................................................................11
3.4. Baseline Variables...................................................................................................11
3.5. Safety Endpoints .....................................................................................................11
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................12
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................13
5.1. Hypotheses and Decision Rules ..............................................................................13
5.2. General Methods .....................................................................................................13
5.2.1. Analyses for Continuous Endpoints ...........................................................13
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Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 3 of 26
5.2.2. Analyses for Categorical Endpoints ...........................................................13
5.2.3. Mixed Effect Model....................................................................................13
5.3. Methods to Manage Missing Data ..........................................................................14
5.3.1. Plasma Pharmacokinetic Parameters ..........................................................14
6. ANALYSES AND SUMMARIES ......................................................................................15
6.1. Primary Endpoint(s) ................................................................................................15
6.1.1. Adverse Events ...........................................................................................15
6.1.2. Laboratory Data..........................................................................................15
6.1.3. Vital Signs ..................................................................................................15
6.1.4. Electrocardiograms.....................................................................................16
6.1.5. Continuous Cardiac Monitoring .................................................................17
6.1.6. Neurological Examinations ........................................................................17
6.1.7. Physical Examination .................................................................................17
6.2. Secondary Endpoints...............................................................................................17
6.3. Other Endpoints.......................................................................................................19
6.3.1. Additional Plasma PF-07853578 PK Parameters.......................................19
6.3.2. Plasma PF-07853578 PK Parameters During Food Effect Period (if 
conducted)........................................................................................................19
6.3.3. Plasma PF-07853578 PK Parameters During IDS Oral Solution 
Period (if conducted)........................................................................................19
6.3.4. Banked Biospecimens.................................................................................20
6.4. Subset Analyses.......................................................................................................20
6.5. Baseline and Other Summaries and Analyses.........................................................20
6.5.1. Baseline Summaries....................................................................................20
6.5.2. Study Conduct and Participant Disposition................................................20
6.5.3. Study Treatment Exposure .........................................................................20
6.5.4. Concomitant Medications and Non-drug Treatments.................................20
6.6. Safety Summaries and Analyses .............................................................................20
7. INTERIM ANALYSES.......................................................................................................20
7.1. Introduction .............................................................................................................20
7.2. Interim Analyses and Summaries............................................................................21
APPENDICES .........................................................................................................................22
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Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 4 of 26
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................5
Table 2. Summary of PF-07853578 plasma PK parameters to be calculated..........................11
Table 3. Additional PF-07853578 Plasma PK Parameters......................................................11
Table 4. Summary Statistics for PF-07853578 Plasma PK Parameters...................................17
Table 5. 
Summary statistics to be produced for additional plasma PK 
Parameters for PF-07853578 ....................................................................19
LIST OF FIGURES
Figure 1. Study Design: Interleaving, Placebo-Controlled, 4-Period, Crossover Design..........6
APPENDICES
Appendix 1. PK Analyses – Example of SAS Code for mixed effects model ........................23
Appendix 2. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern .....24
Appendix 3. List of Abbreviations...........................................................................................25
NOTE: Italicized text within this document has been taken verbatim from the protocol.
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Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 5 of 26
1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
1
23-Jun-2023
Final Protocol 
Amendment 1, 
06 June 2023
N/A
N/A
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C5161001. This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition or its analysis will also be reflected in a protocol amendment.
Text in italics is taken directly from the protocol.
2.1. Modifications to the Analysis Plan Described in the Protocol
No modifications.
2.2. Study Objectives, Endpoints, and Estimands
Type
Objective
Endpoint
Primary: 
Primary: 
Safety
Section 6.1
To evaluate the safety and tolerability of 
single ascending doses of PF-07853578 
administered orally to healthy adult 
participants.
Assessment of AEs, clinical safety laboratory tests, 
vital signs, continuous cardiac monitoring, 12-
lead ECGs, PEs, and neurological examinations.
Secondary: 
Secondary: 
PK
Section 6.2
To evaluate the PK of PF-07853578 
following single doses of PF-07853578 
administered orally to healthy adult 
participants.
PK parameters derived from plasma PF-07853578 
concentrations: Cmax, Tmax, AUClast, and if data 
permit, AUCinf and t½.
Tertiary/Exploratory: 
Tertiary/Exploratory: 
PK 
Section 6.3.1
To evaluate additional PK parameters of 
PF-07853578 following single doses of 
PF-07853578 administered orally to 
healthy adult participants.
Additional PK parameters derived from plasma 
PF-07853578 concentrations: Cmax(dn), 
AUClast(dn), and if data permit, AUCinf(dn), CL/F, 
and Vz/F.
PK 
Section 6.3.2
To evaluate the effect of food on the PK of 
PF-07853578 following single doses of 
PF-07853578 administered orally to 
healthy adult participants (if conducted).
PK parameters derived from plasma PF-07853578 
concentrations after a high-fat/high-calorie meal: 
Cmax, Tmax, AUClast, and if data permit, AUCinf and 
t½.
PK 
Section 6.3.3
To evaluate the PK of PF-07853578 
following single oral doses of an IDS oral 
solution of PF-07853578 administered 
orally to healthy adult participants (if 
conducted).
PK parameters derived from plasma PF-07853578 
concentrations after IDS oral solution dosing: 
Cmax, Tmax, AUClast, and if data permit, AUCinf and 
t½.
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Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 6 of 26
There are no estimands for this study.
2.3. Study Design
This study is a randomized, investigator- and participant-blind, sponsor-open, 
placebo-controlled, FIH, single ascending dose, 4-period, crossover, interleaving design 
study of PF-07853578 orally administered to healthy adult participants. Approximately 
24 healthy adult participants (up to 3 cohorts of approximately 8 participants each) will be 
enrolled in this study. The optional third cohort will only be used if the objectives of the study 
are not fulfilled in Cohort 1 and Cohort 2. Each participant is planned to undergo 
4 treatment periods receiving up to 4 doses of PF-07853578 and up to 2 doses of placebo. In 
each period, participants will be randomized to either PF-07853578 or placebo in a ratio of 
6:2. A diagram of the study design is shown in Figure 1.
Precautionary sentinel dosing will be used in any period evaluating escalating doses of 
PF-07853578. Two participants (1 receiving PF-07853578 and 1 receiving placebo) within a 
period will be dosed initially before the remaining participants of that period are dosed. 
Safety and tolerability data through at least 24 hours post-dose for the sentinel participants 
will be reviewed prior to dosing the remaining participants of that period. Sentinel dosing 
may be omitted when repeating a dose level or administering a lower dose level than 
previously evaluated.
Figure 1. Study Design: Interleaving, Placebo-Controlled, 4-Period, Crossover Design
Screening activities will be completed over the 28 days prior to randomization in Period 1. In 
each period, participants will be admitted to the CRU on Day -1 and will remain in the CRU 
through at least the 72-hour assessments on Day 4. Participants may remain in the CRU 
after completion of Day 4 activities at the discretion of the investigator or if safety, 
tolerability, or PK data dictate the need to prolong confinement in the CRU. Participants will 
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Protocol C5161001 (PF-07853578) 
Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
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Page 7 of 26
receive a single oral dose of PF-07853578 or placebo on Day 1 of each period. Dose levels 
will be escalated to bracket the expected clinical dose range, but the projected exposures will 
not exceed the predefined human exposure limits. Within an individual participant, there will 
be a washout interval of at least 10 days between doses. The total duration of participation 
from the screening visit to the telephone follow-up contact will be approximately 17 weeks 
for each participant. Participants will return for an on-site follow-up visit 7-10 days after the 
final dose of study intervention. The follow-up contact may occur via telephone contact and 
must occur 28-35 days after administration of the final dose of study intervention. 
Dosing will occur in the fasted state for all periods, except if an optional exploratory 
assessment of the effect of food on PF-07853578 PK is conducted. If the food effect is 
evaluated, it is anticipated that study intervention will be administered in the fed state in the 
last period of Cohort 2 or Cohort 3 at a dose level that was previously administered fasted 
within the same cohort. However, study intervention may be administered in the fed state 
during any of the study periods/cohorts if thought necessary to achieve study objectives. The 
actual dose level will be selected based on emerging safety, tolerability, and PK data but will 
be expected to achieve approximate projected therapeutic exposures. 
If evaluated, the IDS oral solution of PF-07853578 is anticipated to be assessed in the last 
period of Cohort 2 or Cohort 3 at a dose level that was previously administered as a 
suspension within the same cohort. However, the IDS oral solution may be administered 
during any of the study periods/cohorts if thought necessary to achieve study objectives.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
Primary endpoints include assessment of adverse events (AEs) and treatment-emergent 
adverse events (TEAEs), clinical safety laboratory abnormalities, vital signs, ECG 
parameters, cardiac monitoring, and physical and neurological examinations during the entire 
study, by period. 
Any events occurring following start of study intervention (ie, treatment with PF-07853578 
or placebo) will be counted as treatment emergent. 
Events that occur in a non-treatment period (eg, washout or follow-up) will be counted as 
treatment emergent and attributed to the most recent treatment taken.
A 3-tier approach for summarizing adverse events (AEs) will not be used due to the low 
number of participants planned to be recruited. 
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters):

adverse events,

laboratory data (except data from screening visit),

vital signs data,
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
ECG results,

cardiac monitoring, 

physical examinations, 

neurological examinations.
3.1.1. Adverse Events
An AE is considered a TEAE if the event started during the effective duration of treatment. All 
events that start on or after the first dose of study intervention, but before the end of the study 
will be flagged as TEAEs. The algorithm will not consider any events that started prior to the 
first dose date.
3.1.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol.
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory test findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition.
Baseline will be the last pre-dose measurement in each study period.
To determine if there are any clinically significant laboratory abnormalities, the hematological, 
clinical chemistry (serum) and urinalysis safety tests will be assessed against the criteria 
specified in the sponsor reporting standards. The assessment will take into account whether 
each participant’s baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter.
3.1.3. Vital Signs
Single supine blood pressure and pulse rate measurements will be taken at screening, follow-
up visit and at early termination (if applicable). Triplicate supine measurements will be taken 
at all other times as detailed in the Schedule of Activities (SoA) in the protocol. The average 
of the triplicate measurements will be calculated prior to analyzing the data. Respiratory rate 
will be measured at each timepoint specified in the protocol.
Baseline for these measures will be defined as the last pre-dose measurement in each study 
period.
The following endpoints will be determined:

Change from baseline (CFB) in systolic and diastolic BP, pulse rate and respiratory rate

The minimum and maximum post-dose systolic and diastolic BP, pulse rate and 
respiratory rate

The maximum increase and decrease from baseline over all measurements taken post-
dose for systolic and diastolic BP, pulse rate and respiratory rate values
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The maximum decrease and increase from baseline over all measurements taken post-dose will 
be calculated for supine systolic and diastolic blood pressures and pulse rates. The maximum 
increase from baseline will be calculated by selecting the maximum change from baseline over 
the respective period, except in the case where a participant does not show an increase. In such 
an instance, the minimum decrease should be taken. Similarly, the maximum decrease from 
baseline will be determined by selecting the minimum value of the change from baseline. In 
cases where a participant does not show a decrease, the minimum increase should be taken.
3.1.4. Electrocardiograms
A single 12-lead ECG will be obtained on all participants at screening, follow-up visit and at 
early termination (if applicable). 12-lead ECGs will be recorded in triplicate at all other times 
as detailed in the SoA in the protocol. The average of the triplicate readings collected at each 
assessment time will be calculated for each ECG parameter.
The average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1H, 
-0.5H, and pre-dose 0H; total of 9 ECG measurements) collected before morning dose 
administration on Day 1 will serve as each participant’s baseline value in each study period.
ECG endpoints include heart rate, QT interval, PR interval and QTcF and QRS complex. If 
not supplied QTcF will be derived using Fridericia’s heart rate correction formula:
QTcF = QT / (RR)1/3 where RR = 60/HR (if RR not provided).
The following endpoints will be determined:

Change from baseline in QT, QTcF, PR, QRS interval and heart rate

The maximum post-dose QTcF, heart rate, PR and QRS interval

The maximum increase from baseline over all measurements taken post-dose for QTcF, 
heart rate, PR and QRS values
The maximum increase from baseline will be calculated by selecting the maximum change 
from baseline over the respective period, except in the case where a participant does not show 
an increase.  In such an instance, the minimum decrease should be taken.
3.1.5. Continuous Cardiac Monitoring
Continuous cardiac monitoring will be performed using telemetry as outlined in the protocol.
All abnormal rhythms will be recorded and reviewed by the study physician for the presence 
of rhythms of potential clinical concern. The time, duration, and description of the clinically 
significant event will be recorded in the CRF.
Events deemed of clinical concern will be recorded as AEs and will be summarized as part of 
the standard AE outputs.
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3.1.6. Neurological examinations 
Neurological examinations may be conducted by a physician, trained physician's assistant, 
or nurse practitioner as acceptable according to local regulation at the nominal time points 
specified in the SoA. The neurological exam will consist of assessment of higher cortical 
function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and
coordination and gait. Additional neurological examinations that are outside of SoA (eg, to
evaluate an AE) may be conducted at the discretion of investigator. All neurological exams
should be done to the extent needed to assess the participant for any potential changes in
neurological status, as determined by the investigator (or designee). Changes in the timing 
or addition of timepoints for the neurological examinations may occur based on emerging 
data.
Any untoward neurological examination findings that are identified during the active collection 
period will be captured as AEs or SAEs, if those findings meet the definition of an AE or SAE, 
and will be summarized as part of the standard AE outputs.
3.1.7. Physical Examinations
Complete physical examinations will be conducted at screening or upon admission for a 
participant’s first period in the study. At all other timepoints, a brief physical exam may be 
performed for the findings during a previous exam or new/open AEs at the investigators 
discretion. Height and weight will only be measured at the screening visit.
Physical examination findings collected during the study will be considered source record and 
will not be required to be reported, unless otherwise noted. 
Any untoward physical examination findings that are identified during the active collection 
period will be captured as AEs or SAEs, if those findings meet the definition of an AE or SAE, 
and will be summarized as part of the standard AE outputs.
3.2. Secondary Endpoint(s)
Blood samples for PK analysis of PF-07853578 will be taken according to the SoA in the 
protocol.
The plasma PK parameters for PF-07853578, following oral dose administration, will be 
derived from the plasma concentration-time profiles using standard noncompartmental 
methods as detailed in Table 2, as data permit. Table 2 shows the analysis scale and method 
for each parameter.
In all cases, actual PK sampling times will be used in the derivation of PK parameters. If actual 
PK sampling times are not available, nominal PK sampling times will be used in the derivation 
of PK parameters.
The following plasma PK parameters as described in Table 2 will be determined:
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Table 2. Summary of PF-07853578 plasma PK parameters to be calculated.
Parameter
Analysis Scale
PF-07853578
AUCinf*
ln
A, D
AUClast
ln
A, D
Cmax
ln
A, D
Tmax
R
D
t½*
R
D

*=if data permits. Abbreviations: A=analyzed using a statistical model (if applicable); D=displayed with 
descriptive statistics as outlined in Table 4 in Section 6.2; ln=natural-log transformed; R = raw 
(untransformed).
3.3. Other Endpoint(s)
3.3.1. Additional Plasma PF-07853578 PK Parameters
Additional plasma PF-07853578 PK parameters, as described in Table 3, will be determined:
Table 3. Additional PF-07853578 Plasma PK Parameters
Parameter
Analysis Scale
PF-07853578
AUCinf (dn)*
ln
D
AUClast (dn)
ln
D
Cmax (dn)
ln
D
CL/F*
ln
D
Vz/F*
ln
D
*=if data permits. Abbreviations: D=displayed with descriptive statistics as 
outlined in Table 5 in Section 6.3.1 ; dn = normalized to a 1 mg PF-07853578 dose; ln=natural-log transformed; 
R = raw (untransformed).
3.3.2. Plasma PF-07853578 PK Parameters During Food Effect Period (if conducted)
The plasma PF-07853578 PK parameters described in Table 2 and Table 3 will also be 
determined during the fed period. 
3.3.3. Plasma PF-07853578 PK Parameters During IDS Oral Solution Period (if 
conducted)
The plasma PF-07853578 PK parameters described in Table 2 and Table 3 will also be
determined after IDS oral solution administration. 
3.4. Baseline Variables
Not applicable.
3.5. Safety Endpoints
See Section 3.1 for details.
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4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
Participant Analysis Set
Description
Applicable Analysis
(for additional 
information refer to
Section 6)
Enrolled 
“Enrolled” means a participant’s, or 
their legally authorized representative’s, 
agreement to participate in a clinical 
study following completion of the 
informed consent process and 
randomization to study intervention. A 
participant will be considered enrolled if 
the informed consent is not withdrawn 
prior to participating in any study activity 
after screening. Potential participants 
who are screened for the purpose of 
determining eligibility for the study, but 
do not participate in the study, are not 
considered enrolled, unless otherwise 
specified by the protocol.
Evaluable
All participants assigned to study 
intervention and who take at least 1 dose 
of study intervention.
Safety analysis set
All participants randomly assigned to 
study intervention and who take at least 1 
dose of study intervention. Participants 
will be analyzed according to the study 
intervention they actually received.
Section 6.1
Safety Summaries 
and Analyses 
PK Concentration Set
All participants randomly assigned to 
study intervention and who receive at 
least 1 dose of study intervention and in 
whom at least 1 plasma concentration 
value is reported.
Section 6.2, Section 
6.3.1, Section 6.3.2, 
Section 6.3.3
PK Endpoints
PK Parameter Set
All participants randomly assigned to 
study intervention and who receive at 
least 1 dose of study intervention and 
have at least 1 of the PK parameters of 
interest calculated.
Section 6.2, Section 
6.3.1, Section 6.3.2, 
Section 6.3.3
PK Endpoints
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5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
There is no statistical hypothesis testing planned for this study, and no statistical decision 
rules will be applied.
5.2. General Methods
Unless otherwise stated, all summaries and plots will be presented by dose and treatment as 
applicable. Each formulation of PF-07853578 administered during the study and fasting status 
will be considered as separate treatments.
Unless otherwise stated the summary tables and/or statistical analyses will only include a single 
pooled placebo group across all included cohorts. Placebo will be pooled from all dose 
escalation periods but not for the fed period (if conducted) and for IDS oral solution period (if 
conducted).
5.2.1. Analyses for Continuous Endpoints
Unless otherwise stated, continuous variables will be presented using summary statistics: 
number of observations, arithmetic mean, standard deviation, median, minimum and 
maximum values.
5.2.2. Analyses for Categorical Endpoints
Categorical variables will be presented using summary statistics: number of observations and 
percentages.
5.2.3. Mixed Effect Model
A mixed effects model with treatment as a fixed effect and participant as a random effect will 
be used for analysis of the:

Effect of food on PF-07853578 PK

PF-07853578 PK of IDS oral solution relative to the oral suspension formulation.
Estimates of the adjusted (least squares) mean differences (Test-reference) and corresponding 
90% confidence intervals will be obtained from the model. The adjusted mean differences 
and 90% confidence intervals for the differences will be exponentiated to provide estimates 
of the ratio of adjusted geometric means (Test/Reference) and 90% confidence intervals for 
the ratios.
The mixed effects model will be implemented using SAS Proc Mixed, with REML 
estimation method and the Kenward-Roger degrees of freedom algorithm.
Residuals from the models will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals, but these will not be included in the clinical study report. If there are major 
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deviations from normality or outliers (where studentized [conditional] residuals are greater 
than 3 or less than -3), then the effect of these on the conclusions may be investigated 
through alternative transformations and/or analyses excluding outliers. Justification for any 
alternative to the planned analysis will be given in the report of the study if applicable.
Example code is shown in Appendix 1.
5.3. Methods to Manage Missing Data
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
In all PK data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. In listings BLQ values will be reported as “<LLOQ”, where LLOQ 
will be replaced with the value for the LLOQ.
In PK summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if one of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie,no sample),
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist/statistician.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
Participants who experience events that may affect their PK profile (e.g., lack of compliance 
with dosing or vomiting) may be excluded from the PK analysis. At the discretion of the 
pharmacokineticist, a concentration value may also be excluded if the deviation in sampling 
time is of sufficient concern or if the concentration is anomalous for any other reason.
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
5.3.1. Plasma Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of plasma PK parameters.
If a PK parameter cannot be derived from a participant’s concentration data, the parameter 
will be coded as NC (i.e., not calculated). (Note that NC values will not be generated beyond 
the day that a participant discontinues.)
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular treatment group/analyte with ≥3 evaluable measurements. 
For statistical analyses (i.e., mixed effects model), PK parameters coded as NC will also be 
set to missing; and analyses will not be performed for a particular parameter if more than 
50% of the data are NC.
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If an individual participant has a known biased estimate of a plasma PK parameter (due, for 
example, to an unexpected event such as vomiting before all the compound is adequately 
absorbed in the body), this will be footnoted in summary tables and may not be included in 
the calculation of summary statistics or statistical analyses.
6. ANALYSES AND SUMMARIES
For all presentations, study day will refer to the day within a particular treatment period, 
unless otherwise specified.
6.1. Primary Endpoint(s)
6.1.1. Adverse Events
AEs will be summarized by dose and treatment (if applicable) and overall and in accordance 
with sponsor reporting standards using the safety population defined in Section 4.
Incidence and severity of TEAE tables will additionally be produced (‘All causality’ and 
‘Treatment related,’ separately) to summarize the total number of adverse events by preferred 
term, which will be reported by dose and treatment (if applicable) and overall, in accordance with 
sponsor reporting standards using the safety analysis set defined in Section 4.
The AEs will be presented sorted in descending frequency based on the overall number of 
AEs (by preferred term or system order class as appropriate) across treatments.
6.1.2. Laboratory Data
Safety laboratory data will be listed and summarized by dose and treatment (if applicable) 
and overall, in accordance with the sponsor reporting standards using the safety population 
defined in Section 4 . 
In summary and listing tables, laboratory abnormalities occurring pre-dose on Day -1 for 
each period starting with Period 2, will be attributed to the treatment from the previous 
period (eg, for Cohort 1, an occurrence pre-dose at Period 2 Day -1 will be attributed to the 
Period 1 dose). 
6.1.3. Vital Signs
Absolute values and changes from baseline (as defined in Section 4) in supine systolic and 
diastolic blood pressure, respiratory rate, and pulse rate will be listed, and summarized by 
dose and treatment (if applicable) and time point, according to sponsor reporting standards 
using the safety population defined in Section 4.
Mean absolute values and mean changes from baseline for systolic and diastolic blood 
pressure, respiratory rate, and pulse rate will be plotted against time point. On each plot,
there will be 1 line for each treatment with all treatments on the same plot. Corresponding 
individual plots of changes from baseline will also be produced for each treatment.
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Maximum and minimum absolute values and changes from baseline (as defined in Section 
3.1) for supine vital signs will also be summarized descriptively by dose and treatment (if 
applicable) using categories as defined in Appendix 2. 
Numbers and percentages of participants meeting the categorical criteria will be provided. 
All planned and unplanned post dose time points will be counted in these categorical 
summaries. All values meeting the criteria of potential clinical concern will be listed.
Values meeting the categorical criteria occurring pre-dose on Day 1 for each period starting 
with Period 2, will be attributed to the treatment from the previous period (e.g., for cohort 1, 
an occurrence pre-dose at Period 2 Day 1 will be attributed to the Period 1 dose). 
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. 
6.1.4. Electrocardiograms
Absolute values and changes from baseline in QT, heart rate, QTcF, PR and QRS will be 
summarized by dose and treatment (if applicable) and timepoint using sponsor reporting 
standards, using the safety analysis set defined in Section 4. Baseline is as defined in Section 
3.1.4 .
Mean changes from baseline in QT, heart rate and QTcF will be plotted against time post-dose. 
On each plot there will be one line for each treatment. Corresponding individual plots of 
changes from baseline will also be produced for each treatment.
Changes from baseline in QTcF will also be plotted separately against drug concentrations of 
PF-07853578. This will be a scatter plot for all observations where QTcF and drug 
concentration are recorded. Placebo data will also be included (with drug concentration set to 
zero). Different symbols will be used for each treatment.
Maximum increase from baseline for QTcF, heart rate, PR and QRS values will be summarized 
by dose and treatment (if applicable) according to sponsor reporting standards. 
ECG endpoints and changes from baseline (QTcF, PR and QRS) will also be summarized 
descriptively by dose and treatment (if applicable) using categories as defined in Appendix 2 . 
Numbers and percentages of participants meeting the categorical criteria will be provided. All 
planned and unplanned postdose time points will be counted in these categorical summaries.  
Values meeting the categorical criteria occurring pre-dose on Day 1 for each period starting 
with Period 2, will be attributed to the treatment from the previous period (e.g., for cohort 1, 
an occurrence pre-dose at Period 2 Day 1 will be attributed to the Period 1 dose).
Listings of participants with any single post-dose value >500msec will also be produced for 
QTcF.
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. 
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6.1.5. Continuous Cardiac Monitoring
Continuous cardiac monitoring will be performed using telemetry as outlined in the protocol. 
Data will be reviewed and summarized on an ongoing basis during the study to evaluate the 
safety of participants.
All abnormal rhythms will be recorded and reviewed by the investigator for the presence of 
rhythms of potential clinical concern.  The time, duration, and description of the clinically 
significant event will be recorded in the CRF.  Events deemed of clinical concern will be 
recorded as AEs and will be summarized as part of the standard AE outputs.
6.1.6. Neurological Examinations
Neurological examinations will be performed as outlined in the protocol. Data will be reviewed 
and summarized on an ongoing basis during the study to evaluate the safety of participants.
All abnormality will be recorded and reviewed by the investigator for the presence of 
neurological examination findings of potential clinical concern. The time, duration, and 
description of the clinically significant event will be recorded in the CRF.  Events deemed of 
clinical concern will be recorded as AEs and will be summarized as part of the standard AE 
outputs.
6.1.7. Physical Examination
Physical examinations will be performed as described in the protocol.  
Medical history and physical examination as applicable, collected during the course of the 
study will be considered source data and will not be required to be reported, unless otherwise 
noted. However, any untoward findings identified on physical examinations conducted during 
the active collection period will be captured as AEs, if those findings meet the definition of an 
AE, and will be summarized as part of the standard AE outputs.
Data collected at screening that are used for inclusion/exclusion criteria, will be considered 
source data, and will not be required to be reported, unless otherwise noted. 
6.2. Secondary Endpoints
Plasma PK parameters for PF-07853578, as described in Section 3.2, will be listed and 
summarized descriptively for participants in the PK Parameter Set (as defined in Section 4). 
Missing values will be handled as detailed in Section 5.3. Each PK parameter will be 
summarized by dose (and formulation and fasting condition, if appropriate) as applicable.
Table 4. Summary Statistics for PF-07853578 Plasma PK Parameters 
Parameter
Summary Statistics
AUClast, AUCinf*, and Cmax
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum, geometric mean and geometric 
cv%.
Tmax
N, median, minimum, maximum. 
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t½.*
N, arithmetic mean, standard deviation, median, 
minimum, maximum. 
*: if data permit
Supporting data from the estimation of AUCinf will be listed by dose and treatment (if 
applicable): terminal phase rate constant (kel); goodness of fit statistic from the log-linear 
regression (r2); the percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, 
and number of time points used in the estimation of kel. This data may be included in the 
clinical study report.
The following plots will be presented using the PK Parameter Set (as defined in Section 4):

Box and whisker plots for dose-normalized PK parameters [AUCinf (dn), AUClast (dn)
and Cmax(dn)] will be presented in logarithmic scale by dose and treatment (if 
applicable) and overlaid with observed values of individual participants and 
geometric means. Geometric means will have a different symbol than the individual 
values. Individual values from different cohorts will also have a different symbol. A
footnote will be added to the plots to indicate that geometric means are presented and 
that data from all cohorts are presented on the plot.
The following will additionally be presented for the plasma concentration data using the PK 
Concentration Set (as defined in Section 4): 
-
a listing of all concentrations sorted by participant ID and nominal time post-dose for 
each dose and treatment (if applicable) separately. The concentration listing will also 
include the actual times. Deviations from the nominal time will be given in a separate 
listing. 
-
a summary of concentrations by each nominal time post-dose (produced separately for 
each dose and treatment (if applicable)), where the set of statistics will include n, mean, 
median, standard deviation, coefficient of variation (cv), minimum, maximum and the 
number of concentrations above the lower limit of quantification. 
-
median concentration time plots (on both linear and semi-log scales) against nominal 
time post-dose by dose and treatment (if applicable). One plot for each scale will be 
presented, which will include all doses and treatments in the same plot.
-
individual concentration time plots by dose (on both linear and semi-log scales) against 
actual time post-dose (there will be separate spaghetti plots for each dose and treatment 
(if applicable), with a line for each participant per scale).
-
individual concentration time plots by participant (on both linear and semi-log scales) 
against actual time post-dose. 
The nominal PK sampling time will be used for summary statistics and relevant median plots, 
whereas for individual participant plots by time, the actual PK sampling time will be used.
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6.3. Other Endpoints
6.3.1. Additional Plasma PF-07853578 PK Parameters
Additional plasma PK parameters for PF-07853578, as described in Section 3.3.1, will be 
listed and summarized descriptively as described in Table 5 for participants in the PK 
Parameter Set (as defined in Section 4). 
Missing values will be handled as detailed in Section 5.3.
Each PK parameter will be summarized by dose (and formulation and fasting condition, if 
appropriate) as applicable as required in the table below:
Table 5. Summary statistics to be produced for additional plasma PK Parameters for
PF-07853578 
Parameter
Summary Statistics
Cmax(dn), AUClast(dn), 
AUCinf(dn) *, CL/F*, and 
Vz/F*
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum, geometric mean and geometric 
cv%.
*: if Data Permit
The nominal PK sampling time will be used for summary statistics and relevant median 
plots, whereas for individual participant plots by time, the actual PK sampling time will be 
used.
6.3.2. Plasma PF-07853578 PK Parameters During Food Effect Period (if conducted)
Plasma PK parameters for PF-07853578 on Fed State as described in Section 3.3.2 will be 
listed and summarized descriptively as described in Section 6.2 for participants in the PK 
Parameter Set as defined in Section 4.
Natural loge transformed AUCinf (as data permit), AUClast, and Cmax (dose-normalized prior 
to analysis, if appropriate) of PF-07853578 on fasted state or on fed state will be analyzed 
using a mixed effect model as described in Section 5.2.3, using only data from the respective 
periods that includes the two treatments of interest. The test treatment will be PF-07853578
administered with food in comparison to the reference treatment of PF-07853578
administered on fasted state.
6.3.3. Plasma PF-07853578 PK Parameters During IDS Oral Solution Period (if 
conducted)
Plasma PK parameters for PF-07853578 as described in Section 3.3.3 will be listed and 
summarized descriptively as described in Section 6.2 for participants in the PK Parameter Set 
as defined in Section 4. .
Natural loge transformed AUCinf (as data permit), AUClast , and Cmax (dose-normalized prior 
to analysis, if appropriate) of PF-07853578 administered as a suspension or administered as 
IDS oral solution will be analyzed using a mixed effect model as described in Section 5.2.3, 
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using only data from the respective periods that includes the two treatments of interest. The 
test treatment will be PF-07853578 administered as IDS oral solution in comparison to the 
reference treatment of PF-07853578 administered as a suspension.
6.3.4. Banked Biospecimens 
Banked biospecimens will be collected and retained for future analyses but will not be 
analysed specifically for this study and will not be included in the CSR.
6.4. Subset Analyses
No subset analyses will be performed.
6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Demographics data (age, biological sex, race, ethnicity, body weight, body mass index and 
height) will be summarized across all participants in the safety population (as defined in
Section 4) as described in Section 5.2.1 or Section 5.2.2 (as appropriate).
6.5.2. Study Conduct and Participant Disposition
Participant evaluation groups will show end of study participant disposition by dose and/or 
treatment when applicable and overall and will show which participants were analyzed for 
PK and safety, which may not be produced in one table. Frequency counts and percentages 
will be supplied for participant discontinuation(s) by dose and/or treatment when applicable.
6.5.3. Study Treatment Exposure
Not applicable.
6.5.4. Concomitant Medications and Non-drug Treatments
All prior and concomitant medication(s) as well as non-drug treatment(s) will be provided in 
listings.
6.6. Safety Summaries and Analyses
See Section 6.1.
7. INTERIM ANALYSES
7.1. Introduction
No interim analysis will be conducted for this study. 
However, preliminary draft safety and PK data will be reviewed after each study period. This 
is a sponsor-open study, with the investigator and participant blinded to study treatment. A 
limited number of Pfizer personnel (eg, PK assay specialist, medical monitor, clinical lead, 
study clinician, statistician, clinical programmer, and clinical pharmacology lead) will be 
unblinded to treatments in order to permit real-time interpretation of the safety and 
pharmacokinetic data, and to provide information necessary for dose escalation decisions and 
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to potentially alter the dose escalation sequence. To minimize the potential for bias, treatment 
randomization information will be kept confidential by Pfizer personnel and will not be 
released to the investigator/study staff until the conclusion of the study. Unblinding will not 
be performed until the final database has been locked for all cohorts. Final analysis will 
follow the official database release.
7.2. Interim Analyses and Summaries
Not applicable.
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APPENDICES
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Appendix 1. PK Analyses – Example of SAS Code for mixed effects model
An example of the PROC MIXED code:
proc mixed data=tab.pk; 
class trt subject;
model &var = trt / ddfm=KR;
random subject /subject=subject;
lsmeans trt/ diff cl alpha=0.1; 
run;
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Appendix 2. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern
Categories for QTcF
Absolute value of QTcF 
(msec)
450 and 480
>480 and 500
>500
Increase from baseline in 
QTcF (msec)
30 and 60
>60
Categories for PR and QRS
PR (msec)
max. ≥300
PR (msec) increase 
from baseline
Baseline >200 and 
max. ≥25% increase
Baseline ≤200 and 
max. ≥50% increase
QRS (msec)
max. ≥140
QRS (msec) increase 
from baseline
≥50% increase
Categories for Vital Signs
Systolic BP (mm Hg)
min. <90
Systolic BP (mm Hg) change from baseline
max. decrease ≥30
max. increase ≥30
Diastolic BP (mm Hg)
min. <50
Diastolic BP (mm Hg) change from baseline
max. decrease ≥20
max. increase ≥20
Supine pulse rate (bpm)
min. <40
max. >120
Measurements that fulfill these criteria are to be listed in the report.
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Appendix 3. List of Abbreviations
Abbreviation
Term
AE
Adverse Event
AUC
Area Under the Curve
AUCinf
Area Under the Concentration-Time Curve from time zero 
extrapolated to infinity
AUCinf (dn)
Dose normalized area Under the Concentration-Time Curve from 
time zero extrapolated to infinity
AUClast
Area Under the Concentration-Time Curve from time zero to the last 
measurable concentration
AUClast (dn)
Dose normalized area Under the Concentration-Time Curve from 
time zero to the last measurable concentration
BLQ
Below the Limit of Quantitation
BP
Blood Pressure
CFB
Change from Baseline
CL 
Clearance
CL/F 
Apparent total body clearance
Cmax
Maximum observed concentration
Cmax (dn)
Dose normalized maximum observed concentration
CRF
Case report form
CRU
Clinical Research Unit
CSR
Clinical Study Report
CV
Coefficient of Variation
ECG
Electrocardiogram
FIH
First in human
H
Hour
HR
Heart rate
ID
Identification
IDS
Intermediate dosage strength
LLOQ
Lower Limit of Quantitation
ln
Natural log
mg
milligram
mmHg
Millimeter of mercury
msec
Millisecond
N
Number of participants
N/A
Not Applicable
NC
Not Calculated
ND
Not Done
NS
No Sample
PE
Physical examination
PK
Pharmacokinetic(s)
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
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Abbreviation
Term
REML
restricted maximum likelihood
SAP
Statistical Analysis Plan
SoA
Schedule of Activities
TEAE
Treatment Emergent Adverse Event
Tmax
Time to maximum observed concentration
t½
Half life
Vz/F 
Apparent volume of distribution
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