A PHASE 1, OPEN-LABEL, PARALLEL-GROUP, SINGLE-DOSE STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF [14C]-PF-07220060 AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-07220060 USING A 14C-MICROTRACER APPROACH
Phase: PHASE1
Conditions: Healthy Participants
Sponsor: Pfizer

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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A P H A S E 1, O P E N -L A B E L, P A R A L L E L -G R O U P, S I N G L E-D O S E S T U D Y I N 
H E A L T H Y A D U L T M A L E P A R TI CI P A N T S T O I N V E S TI G A T E T H E 
A B S O R P TI O N, DI S T RI B U TI O N, M E T A B O LI S M A N D E X C R E TI O N O F 
[1 4C]- P F - 0 7 2 2 0 0 6 0 A N D T O A S S E S S T H E A B S O L U T E BI O A V AI L A BI L I T Y A N D 
F R A C TI O N A B S O R B E D O F P F -0 7 2 2 0 0 6 0 U SI N G A 1 4C- MI C R O T R A C E R 
A P P R O A C H 
St u d y I nter ve nti o n N u m ber :
P F - 0 7 2 2 0 0 6 0
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 4 5, 8 1 4
E U C T N u m ber:
2 0 2 3 - 5 0 7 0 7 4- 4 0- 0 0
Cli nic al Tri als. g o v I D: 
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 4 3 9 1 0 1 0
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 D M E: A St u d y t o U n dersta n d W hat t he B o d y d oes t o t he St u d y  
C o m p o u n d Calle d P F - 0 7 2 2 0 0 6 0 W he n Ta ke n
b y  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.
 

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P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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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 Dece m ber 2 0 2 3
Ori gi nal pr ot oc ol
1 3 Oct o ber 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 gl o bal 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 Dece m ber 2 0 2 3 )
O ver all R ati o n ale f or t he A m e n d me nt: 
T his a me n d me nt is t o a d dress t he re g ulat or y re q uests fr o m Net herla n ds M R E C Part 1 R FI s
date d o n 2 9 N o ve m ber 2 0 2 3 . Please refer t o t he f oll o wi n g ta ble f or t he c ha n ges . 
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
N o n -s u bst a nti al M o dific ati o ns
T o a d d retic ul oc yte c o u nt
t o He mat ol o g y tests i n Ta ble 
5 Pr ot oc ol -Re q uire d 
La b orat or y Assess me nts
T o f ulfill t he re g ulat or y 
re q uest fr o m N L M R E C 
P art 1 R FI date d o n 2 9 
N o ve m ber 2 0 2 3
A p pe n di x 2 Cli nical 
La b orat or y  Tests
T o clari fy t he st u d y is a 
pa rallel-c o h ort st u d y
i ncl u di n g 2 i n de pe n de nt 
c o h orts wit h o ut cr oss o ver . 
C o h orts 1 a n d 2 are e nr olle d 
se q ue ntiall y wit h 1 5 da y s 
differe nce . 
T o f ulfill t he re g ulat or y  
re q uest fr o m N L M R E C part 
1 R FI date d o n 2 9 
N o ve m ber 2 0 2 3
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
T o cl arif y t hat
ra n d o mizati o n i n the te xt 
refers t o all ocati o n 
( n u m ber), as t he st u d y is n ot 
a ra n d o mize d st u d y. 
T o f ulfill t he re g ulat or y 
re q uest fr o m N L M R E C part 
1 R FI date d o n 2 9 
N o ve m ber 2 0 2 3
Secti o n 1. 1 S y n o psis;
Secti o n 4. 1 O verall Desi g n;
Secti o n 6. 3 Assi g n me nt t o 
St u d y  Inter ve nti o n;
Secti o n 9. 2 A nal y sis Sets
G e neral e dit orial c ha n ges
T o c orrect s o me t y p os, a n d 
ma ke mi n or e dits f or 
c o nsiste nc y
T hr o u g h o ut t he pr ot oc ol
 

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P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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T A B L E O F C O N T E N T S
LI S T O F T A B L E S .....................................................................................................................8
1. P R O T O C O L  S U M M A R Y.....................................................................................................9
1. 1. S y n o psis ....................................................................................................................9
1. 2. Sc he ma ....................................................................................................................1 7
1. 3. Sc he d ule of Acti vities .............................................................................................1 8
2. I N T R O D U C TI O N ...............................................................................................................2 6
2. 1. St u d y  Rati o nale.......................................................................................................2 6
2. 2. Bac k gr o u n d .............................................................................................................2 6
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................2 6
2. 2. 2. N o ncli nical P ha r mac o ki netics a n d Meta b olis m .........................................2 7
2. 2. 3. N o ncli nical Safet y ...................................................................................... 2 7
2. 2. 4. Cli nical O ver vie w .......................................................................................2 8
2. 2. 4. 1. Safet y O ver vie w ........................................................................2 9
2. 2. 4. 2. Efficac y  O ver vie w.....................................................................3 0
2. 2. 4. 3. S u m mar y  of P F- 0 7 2 2 0 0 6 0 P har mac o ki netics i n H u ma ns ........ 3 0
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................3 0
2. 3. 1. Ris k Assess me nt......................................................................................... 3 2
2. 3. 2. Be nefit Assess me nt .....................................................................................3 3
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................3 3
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................3 4
4. S T U D Y D E SI G N .................................................................................................................3 5
4. 1. O verall Desi g n .........................................................................................................3 5
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................3 7
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................3 9
4. 3. J ustificati o n f or D ose ..............................................................................................3 9
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................4 0
5. S T U D Y P O P U L A T I ON................................ ......................................................................4 0
5. 1. I ncl usi o n Criteria .....................................................................................................4 0
5. 2. E xcl usi o n Criteria ....................................................................................................4 1
5. 3. L ifest yle C o nsi derati o ns..........................................................................................4 3
5. 3. 1. C o ntrace pti o n ..............................................................................................4 3
 

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P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................4 4
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................4 5
5. 3. 4. Acti vit y .......................................................................................................4 5
5. 4. Scree n Fail ures ........................................................................................................4 5
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 .................................4 6
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................4 6
6. 1. 1. A d mi nistrati o n ............................................................................................4 7
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................4 8
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................4 9
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................5 0
6. 4. Bli n di n g................................ ...................................................................................5 0
6. 4. 1. Bli n di n g of t he S p o ns or.............................................................................. 5 0
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................5 0
6. 6. D ose M o dificati o n ...................................................................................................5 1
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 ......................5 1
6. 8. Treat me nt of O ver d ose................................ ............................................................5 1
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................5 1
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 ...........................................................................5 2
7. 1. Disc o nti n uati o n of St u d y  Inter v e nti o n ....................................................................5 2
7. 1. 1. P ote ntial Cases of Ac ute Ki d ne y  Inj ur y .....................................................5 2
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 .......................................5 3
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................5 4
7. 3. L ost t o F oll o w -U p ...................................................................................................5 4
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 5
8. 1. A d mi nistrati ve Pr oce d ures ......................................................................................5 5
8. 2. Efficac y  Assess me nts..............................................................................................5 6
8. 3. Safet y Assess me nts .................................................................................................5 6
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 6
8. 3. 2. Vital Si g ns ..................................................................................................5 7
8. 3. 2. 1. Bl o o d Press ure a n d P ulse Rate ..................................................5 7
8. 3. 3. Electr ocar di o gra ms..................................................................................... 5 7
 

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Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................5 8
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g .................5 9
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 9
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................6 0
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................... 6 0
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................6 0
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................6 0
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................6 1
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 .....................................................6 1
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................6 1
8. 4. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................6 3
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................6 3
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................6 3
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 3
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 6 3
8. 4. 8. 1. Lac k of Eff icac y........................................................................6 4
8. 4. 9. Me dical De vice Deficie ncies ......................................................................6 4
8. 4. 1 0. Me dicati o n Err ors .....................................................................................6 4
8. 5. P har mac o ki netics ....................................................................................................6 5
8. 5. 1. Plas ma f or P har mac o ki netic A nal ys is of T otal 1 4C Ra di oacti vit y , P F -
0 7 2 2 0 0 6 0 , [1 4C] -P F - 0 7 2 2 0 0 6 0 a n d Meta b olic Pr ofili n g .................................6 5
8. 5. 2. Uri ne a n d Feces f or A nal ys is of P F-0 7 2 2 0 0 6 0, T otal 1 4C 
Ra di oacti vit y  a n d Meta b olic Pr ofili n g.............................................................6 6
8. 5. 3. E mesis (If a n y) ............................................................................................6 7
8. 5. 4. A nal y sis of D osi n g S ol uti o n a n d Deter mi nati o n of A d mi nistere d 
D ose .................................................................................................................6 7
8. 6. Ge netics ...................................................................................................................6 8
8. 6. 1. S pecifie d Ge netics ......................................................................................6 8
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics................................................... 6 8
8. 7. Bi o mar kers ..............................................................................................................6 8
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................6 8
 

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Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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8. 9. Healt h Ec o n o mics ...................................................................................................6 8
8. 1 0. Taste Assess me nt ..................................................................................................6 8
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 6 9
9. 1. Statistical H y p ot heses .............................................................................................6 9
9. 2. A nal y sis Sets ...........................................................................................................6 9
9. 3. Statistical A nal y ses .................................................................................................7 0
9. 3. 1. Pri mar y  E n d p oi nts......................................................................................7 0
9. 3. 1. 1. Mass Bala nce .............................................................................7 0
9. 3. 1. 2. Meta b olic Pr ofili n g a n d Meta b olite I de ntificati o n.................... 7 1
9. 3. 2. Sec o n dar y  P har mac o ki netic E n d p oi nts ......................................................7 1
9. 3. 2. 1. A bs ol ute Oral Bi oa vaila bilit y ....................................................7 1
9. 3. 2. 2. Fracti o n A bs or be d................................ .....................................7 1
9. 3. 2. 3. Safet y A nal ys es .........................................................................7 2
9. 3. 3. Tertiar y  P har mac o ki netic E n d p oi nts ..........................................................7 3
9. 3. 3. 1. Deri vati o n of P har mac o ki netic Para meters ...............................7 3
9. 3. 3. 2. Taste Assess me nt ................................ ......................................7 5
9. 3. 4. Ot her A nal ys es ............................................................................................7 6
9. 4. I nteri m A nal ys es .....................................................................................................7 6
9. 5. Sa m ple Size Deter mi nati o n .....................................................................................7 6
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................................ ..........................................................................7 7
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............7 7
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................7 7
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................7 7
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................7 8
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................7 8
1 0. 1. 4. Data Pr otecti o n .........................................................................................7 9
1 0. 1. 5. C o m mittees Str uct ure ...............................................................................7 9
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ...................................................7 9
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ......................................................7 9
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................8 0
1 0. 1. 8. S o urce D oc u me nts ....................................................................................8 2
 

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Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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1 0. 1. 9. Use of Me dical Rec or ds ............................................................................8 2
1 0. 1. 1 0. St u d y  a n d Site Start a n d Cl os ure ............................................................8 3
1 0. 1. 1 1. P u blicati o n P olic y ...................................................................................8 3
1 0. 1. 1 2. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................8 4
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests.................................................................8 5
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -U p, a n d Re p orti n g .....................................................................8 7
1 0. 3. 1. Defi niti o n of A E .......................................................................................8 7
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................8 8
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 9
1 0. 3. 4. Re p orti n g of S A Es.................................................................................... 9 3
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................9 4
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 9 4
1 0. 4. 2. W o ma n of C hil d beari n g P ote ntial ............................................................9 4
1 0. 4. 3. C o ntrace pti o n Met h o ds .............................................................................9 5
1 0. 5. A p pe n di x 5: Ge netics ............................................................................................9 7
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 8
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 ..........................................1 0 0
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 ............................................................................1 0 0
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 .............1 0 0
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......................................................................................... 1 0 0
1 0. 7. 3. Ki d ne y  F u ncti o n Calc ulati o n T o ols........................................................1 0 1
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 .................................................................................................1 0 1
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................................. 1 0 3
1 0. 9. A p pe n di x 9: Oral S ol uti o n or S us pe nsi o n Palata bilit y  Q uesti o n naire................1 0 5
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns .............................................................................1 1 3
1 1. R E F E R E N C E S ................................................................................................................1 1 8
 

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Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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LI S T O F T A B L E S
Ta ble 1.
Sc he d ule of Acti vit y  ( C o h ort 1-Oral [ 1 4C] -P F - 0 7 2 2 0 0 6 0 
A d mi nistrati o n) .........................................................................................1 8
Ta ble 2.
Sc he d ule of Acti vit y  ( C o h ort 2- Oral u nla bele d P F-0 7 2 2 0 0 6 0 a n d 
I V [1 4C] -P F -0 7 2 2 0 0 6 0 a d mi nistrati o n) .....................................................2 2
Ta ble 3. 
Plas ma P K Para meters Defi niti o ns................................ ...........................7 4
Ta ble 4  
Uri ne P K Para meters Defi niti o ns ................................ .............................7 5
Ta ble 5.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts.............................................8 5
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
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1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: A P hase 1, O pe n -La bel, Parallel -Gr o u p, Si n gle - D ose St u d y i n Healt h y A d ult 
Male Partici pa nts t o I n vesti gate t he A bs or pti o n, Distri b uti o n, Meta b olis m a n d E xcreti o n of 
1 4C- P F -0 7 2 2 0 0 6 0 a n d t o Assess t he A bs ol ute Bi oa vaila bilit y  a n d Fracti o n A bs or be d of 
P F - 0 7 2 20 0 6 0 Usi n g a 1 4C- Micr otracer A p pr oac h
Brief Title: A D M E: A St u d y  t o U n dersta n d W hat t he B o dy d oes t o t he St u d y  C o m p o u n d 
Calle d P F -0 7 2 2 0 0 6 0 W he n Ta ke n b y 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 4 5, 8 1 4
E U C T N u m ber:
2 0 2 3 -5 0 7 0 7 4 -4 0 -0 0
Cli nic al Tri als. g o v I D: 
N ot A p plica ble
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N ot A p plica ble
Pr ot oc ol N u m ber:
C 4 3 9 1 0 1 0
P h ase:
1
R ati o n ale :
P F -0 7 2 2 0 0 6 0 is a selecti ve c y cli n-de pe n de nt ki nase ( C D K) 4 i n hi bit or t hat is c urre ntl y bei n g 
i n vesti gate d i n partici pa nts wit h metastatic or a d va nce d s oli d t u m ors. P F- 0 7 2 2 0 0 6 0 differs 
fr o m c urre ntl y a p pr o ve d d ual C D K 4/ 6 i n hi bit ors i n t hat it dis pla ys greater 
C D K 4 -o ver -C D K 6 selecti vit y  a n d is t heref ore h yp ot hesize d t o dri ve t u m or gr o wt h i n hi biti o n 
t hr o u g h greater C D K 4 selecti vit y, w hile mi ni mizi n g C D K 6 dri ve n he mat o p oetic effects. T his 
ma y  tra nslate t o i m pr o ve d efficac y a n d t olera bilit y o ver ot her C D K 4/ 6 i n hi bit ors.
T he p ur p ose of t he st u d y  will be t o i n vesti gate t he meta b olis m a n d e xcreti o n f oll o win g a 
si n gle oral a d mi nistrati o n of [ 1 4C] P F - 0 7 2 2 0 0 6 0 u n der faste d c o n diti o n i n healt h y male 
partici pa nts. T he data ge nerate d fr o m t his st u d y  will be use d t o assess cleara nce mec ha nis ms 
f or P F - 0 7 2 2 0 0 6 0 as well as i de ntif y meta b olites t hat s h o ul d be q ualifie d t o a d here t o t he 
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 CH) ( M 3) R 2 g ui da nce. I n a d diti o n, t his st u d y will c haracterize t he fracti o n of 
d ose a bs or be d a n d bi oa vaila bilit y of orall y a d mi nistere d P F - 0 7 2 2 0 0 6 0 u n der t he faste d 
c o n diti o n , i n refere nce t o a n i ntra ve n o us (I V) i nf usi o n of [1 4C] P F - 0 7 2 2 0 0 6 0 (gi ve n as a 
micr otracer micr o d ose i nf usi o n f oll o wi n g a d mi nistrati o n of a n oral u nla belle d d ose), a n d will 
als o assess p har mac o ki netic ( P K ) para meters of P F - 0 7 2 2 0 0 6 0 f oll o wi n g b ot h oral a n d I V 
a d mi nistrati o n of [ 1 4C] P F - 0 7 2 2 0 0 6 0. 
T his st u d y  will als o e val uate se ns or y a n d taste attri b utes (e g, bitter ness a n d t o n g ue/ m o ut h 
se nsati o n) of t he P F-0 7 2 2 0 0 6 0 oral s us pe nsi o n t o g ui de t he f ut ure de vel o p me nt of 
p e diatric-frie n dly oral f or m ulati o ns.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0
O 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 c haracterize t he rate a n d e xte nt of 
e xcreti o n of t otal ra di oacti vit y f oll o wi n g 
a d mi nistrati o n of a si n gle oral d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 . 

Mass Bala nce: C u m ulati ve rec o ver y ( %) of 
ra di oacti vit y i n uri ne a n d feces (a dj uste d f or v o mit us,
if a n y), e x presse d as a perce nt of t otal oral ra di oacti ve 
d ose a d mi nist ere d (q ua ntificati o n b y A M S) .

T o c haracterize t he meta b olic pr ofile f or P F -
0 7 2 2 0 0 6 0 a n d i de ntif y t he circ ulati n g a n d 
e xcrete d meta b olites of P F -0 7 2 2 0 0 6 0
f oll o wi n g a d mi nistrati o n of a si n gle oral d ose 
of [ 1 4C] P F -0 7 2 2 0 0 6 0 .

Meta b olic pr ofili n g/ meta b olite i de ntificati o n a n d 
deter mi nati o n of relati ve a b u n da nce of [1 4C] P F -
0 7 2 2 0 0 6 0 a n d its meta b olites i n plas ma, uri ne a n d 
feces, if p ossi ble ( C o h ort 1).
Sec o n d ar y: 
Sec o n d ar y:

T o deter mi ne t he a bs ol ute oral bi oa vaila bilit y 
( F) of P F-0 7 2 2 0 0 6 0 fr o m a si n gle oral d ose 
of P F -0 7 2 2 0 0 6 0 u n der faste d c o n diti o ns 
f oll o we d b y a si n gle I V micr o d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 .

T he rati o of d ose -n or m alize d plas ma A U C i nf of oral 
P F -0 7 2 2 0 0 6 0 ( L C M S) a n d I V [1 4C] P F -0 7 2 2 0 0 6 0
( H P L C-A M S) [ C o h ort 2 o nl y].

T o deter mi ne t he fracti o n of P F -0 7 2 2 0 0 6 0
d ose a bs or be d ( F a) fr o m a si n gle oral d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 u n der faste d c o n diti o ns.

F a calc ulate d fr o m t he rati o of t otal rec o vere d 
ra di oacti vit y [1 4C] i n uri ne f oll o wi n g si n gle d ose 
a d mi nistrati o n of [ 1 4C] P F -0 7 2 2 0 0 6 0 orall y i n C o h ort 1 
a n d via I V i nf usi o n i n C o h ort 2 ( q ua ntificati o n b y 
A M S).

T o deter mi ne t he safet y a n d t olera bilit y of 
P F -0 7 2 2 0 0 6 0 , a d mi nistere d as a si n gle oral 
d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 or a si n gle oral 
d ose of P F -0 7 2 2 0 0 6 0 f oll o we d b y 
a d mi nistrati o n of a si n gle I V d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 .

A E m o nit ori n g, p h ysical e xa mi nati o n, cli nical 
la b orat or y meas ure me nts, vital si g ns a n d 1 2 -lea d 
E C Gs.
A b bre viati o ns: A E = a d verse e ve nt; A M S = accelerat or mass s pectr o metr y; A U C i nf = a rea 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 ; E C G = electr ocar di o gra m; F = oral 
bi oa vaila bilit y ; Fa = fracti o n a bs or be d; H P L C = hi g h perf or ma nce li q ui d c hr o mat o gra p h y ; 
I V = i ntra ve n o us(l y); L C M S = li q ui d c hr o mat o gra p h y mass s pectr o metr y.
O ver all Desi g n :
T his st u d y  will be a P hase 1, o pe n -la bel, parallel- gr o u p , si n gle-d ose st u d y of P F - 0 7 2 2 0 0 6 0 t o 
c haracterize t he meta b olic pr ofile a n d r o utes of e xcreti o n f or oral [1 4C] P F - 0 7 2 2 0 0 6 0 a n d t o 
e val uate t he a bs ol ute oral bi oa vaila bilit y  ( F) of P F - 0 7 2 2 0 0 6 0 a n d fracti o n a bs or be d ( F a) of 
[1 4C] P F - 0 7 2 2 0 0 6 0, i n refere nce t o I V micr otrace r [1 4C] P F - 0 7 2 2 0 0 6 0 i n faste d healt h y male 
partici pa nts.
N u m ber of P artici p a nts:
A p pr o xi matel y  6 healt h y a d ult male partici pa nts will be e nr olle d i n eac h of t he 2 c o h orts. 
Defi niti o n of “e val ua ble partici pa nts” will be pr o vi de d i n t he Statistical A nal y sis Pla n ( S A P).
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 scree ni n g. A partici pa nt will be c o nsi dere d e nr olle d if t he i nf or m e d c o nse nt is 
n ot wit h dra w n pri or t o partici pati n g i n a n y st u d y acti vit y  after scree ni n g. P ote ntial 
partici pa nts w h o are scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y  f or t he st u d y, b ut d o 
n ot partici pate i n t he st u d y, are n ot c o nsi dere d e nr olle d, u n less ot her wise s pecifie d by t he 
pr ot oc ol.
St u d y P o p ul ati o n :
K e y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
Partici pa nts m ust meet t he f oll o wi n g 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 partici pa nts a ge d 1 8 t o 6 5 y ears 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 ys ical 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 o d y mass i n de x ( B MI ) of 1 7. 5 -3 0. 5 k g/ m 2; a n d a t otal b o d y wei g ht > 5 0   k g ( 1 1 0 l b).
3.
E vi de nce of a pers o nall y  si g ne d a n d date d i nf or me d c o nse nt d oc u me nt (I CD)
i n dicati n g t hat t he partici pa nt has bee n i nf or me d of all perti ne nt as pects of t he st u d y.
4.
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.
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).

A n y  c o n diti o n p ossi bl y  affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of h u ma n i m m u n o deficie nc y vir us ( HI V) i nfecti o n, he patitis B, or 
he patitis C; p ositi ve testi n g f or HI V, he patitis B s urface a nti ge n ( H Bs A g), or 
he patitis C a nti b o d y  (H C V A b). He patitis B vacci nati o n is all o we d.
2.
Partici pa nt s wit h a hist or y of irre g ular b o wel m o ve me nts (e g, re g ular e pis o des of 
diarr hea or c o nsti pati o n, irrita ble b o wel s y n dr o me [I B S] or lact ose i nt olera nce).
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
3.
A n y me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/ be ha vi or or la b orat or y a b n or malit y or ot her c o n diti o ns t hat ma y 
i ncrease t he ris k of st u dy partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he 
part ici pa nt i na p pr o priate f or t he st u d y.
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o si n gle oral d ose of st u d y  
i nter ve nti o n.

C o nc o mita nt use of a n y me dicati o ns or s u bsta nces t hat are str o n g i n d ucers or
i n hi bit ors of c yt oc hr o me P 4 5 0 ( C Y P) 3 A 4 or uri di ne
di p h os p hase- gl uc ur o n os yltra nsferase ( U G T) 2 B 7 are pr o hi bite d wit hi n
5 half -li ves pl us 1 4 da ys ( u p t o 2 8 da ys) pri or t o t he si n gle oral d ose of 
P F - 0 7 2 2 0 0 6 0.

Use of pr ot o n -p u m p i n hi bit ors is pr o hi bite d fr o m 2 8 da y s pri or t o t he first d osi n g 
of st u d y  i nter ve nti o n, a n d t hr o u g h t he st u dy . Ot her aci d re d uci n g a ge nts i ncl u di n g 
H 2 -rece pt or a nta g o nists or l ocal a ntaci ds s h o ul d n ot be use d f or at least 7 da ys or 
5 half -li ves, w hic he ver is l o n ger, bef ore t he first d osi n g of st u d y  i nter ve nti o n a n d 
are pr o hi bite d t hr o u g h 5 da y s after t he d osi n g. 
5.
Partici pa nt s u n willi n g or u na ble t o use a re q uire d c o nc o mita nt me dicati o n(s). 
6.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves ( w hic he ver is 
l o n ger) 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. Pre vi o us 
e x p os ure t o P F -0 7 2 2 0 0 6 0 or partici pati o n i n st u dies re q uiri n g P F -0 7 2 2 0 0 6 0 
a d mi nistrati o n.
7.
Partici pa nt s e nr olle d i n a pre vi o us ra di o n ucle oti de st u d y  or w h o ha ve recei ve d 
ra di ot hera py wit hi n 1 2 m o nt hs pri or t o scree ni n g or s uc h t hat t otal ra di oacti vit y  
w o ul d e xcee d acce pta ble d osi metr y .
8.
A p ositi ve uri ne dr u g test. A si n gle re peat f or p ositi ve dr u g scree n ma y be all o we d.
9.
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 y ears, a n d ≥1 5 0/ 9 0 m m H g f or partici pa nts ≥6 0 y ears 
ol d , f oll o wi n g at least 5 mi n utes of s u pi ne rest. If B P is ≥1 4 0 m m H g (sys t olic) or 1 5 0 
m m H g ( base d o n a ge) or ≥9 0 m m H g ( diast olic), t he B P s h o ul d be re peate d 2 m ore 
ti mes a n d t he a vera ge of t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s 
eli gi bilit y.
1 0. Sta n dar d 1 2 -lea d electr ocar di o gra m ( 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 safety or i nter pretati o n of st u d y res ults (e g, 
Q Tc c orrecte d usi n g Fri dericia’s f or m ula [Q Tc F ] > 4 5 0 ms, c o m plete left b u n dle 
bra nc h bl oc k [L B B B ], si g ns of a n ac ute or i n deter mi nate- a ge m y ocar dial i nfarcti o n, 
S T se g me nt a n d T wa ve [S T - T] i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
sec o n d- or t hir d - de gree atri o ve ntric ular [A V ] bl oc k, or seri o us bra d yarr h yt h mias or 
tac hyarr h yt h mias). If Q Tc F e xcee ds 4 5 0 ms, or 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 is 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 h ys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt. 
1 1. T otal 1 4C ra di oacti vit y  meas ure d i n plas ma e xcee di n g 1 1 m B q/ m L.
1 2. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
scree ni n g, as assesse d by t he st u d y s pecific la b orat or y a n d c o nfir me d b y 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), or b ilir u bin 
≥1. 0 5 × u p per li mit of n or mal ( U L N); partici pa nts wit h a hist or y  of Gil bert’s 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤ U L N;

Esti mate d gl o mer ular filtrati o n rate (e G F R) < 6 0 m L/ mi n/ 1. 7 3 m 2 base d o n t he 
2 0 2 1 c hr o nic ki d ne y disease e pi de mi ol o g y (C K D -E PI ) (c o m bi ne d ser u m 
creati ni ne pl us ser u m c y stati n C) e q uati o n;

Bl o o d calci u m or p otassi u m < 0. 9 × l o wer li mit of n or mal (L L N ) or > 1. 1 × U L N ;

A bs ol ute ne utr o p hil c o u nt < 0. 8 × L L N.
1 3. 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) 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 4. Use of t o bacc o or nic oti ne c o ntai ni n g pr o d ucts wit hi n 3 m o nt hs of scree ni n g or a 
p ositi ve uri ne c oti ni ne test (ie, acti ve s m o kers a n d t h ose w h o c urre ntl y  use 
nic oti ne -c o ntai ni n g pr o d ucts are e xcl u de d fr o m partici pati o n i n t his st u d y ). 
1 5. Bl o o d d o nati o n (e xcl u di n g plas ma d o nati o ns) of a p pr o xi matel y  1 pi nt ( 5 0 0 m L ) or 
m ore wit hi n 6 0 da y s pri or t o d osi n g.
1 6. Hist or y  of se nsiti vit y t o he pari n or he pari n-i n d uce d t hr o m b oc yt o pe nia.
1 7. Partici pa nt s w h ose occ u pati o n re q uires e x p os ure t o ra diati o n or m o nit ori n g of 
ra diati o n e x p os ure. 
1 8. 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 pe r vise d by 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. 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
St u d y Ar ms a n d D ur ati o n:
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
[1 4C] P F -0 7 2 2 0 0 6 0
P F -0 7 2 2 0 0 6 0
[1 4C] P F -0 7 2 2 0 0 6 0
T y pe
Dr u g
Dr u g
Dr u g
Use
E x peri me ntal
E x peri me ntal
E x peri me ntal
I M P or A x M P
I M P
I M P
I M P
D ose F or m ul ati o n
Oral s us pe nsi o n  
Oral s us pe nsi o n
I V s ol uti o n
U nit D ose 
Stre n gt h(s)
1 0 0 m g
1 0 0 m g
µ g
D os a ge Le vel(s)
1 0 0 m g, si n gle d ose
1 0 0 m g, si n gle d ose
µ g, si n gle d ose
R o ute of 
A d mi nistr ati o n
Oral
Oral
I V i nf usi o n
St u d y Ar m(s)
A r m  Title
C o h ort 1
C o h ort 2
A r m  T y pe
E x peri me ntal
E x peri me ntal
A r m  Descri pti o n
Oral d ose of 1 0 0 m g 
P F -0 7 2 2 0 0 6 0 c o ntai ni n g  
 n Ci 
[1 4C] ([1 4C] P F -0 7 2 2 0 0 6 0) w ill be
a d mi nistere d as a n 
e xte m p ora ne o usl y pre pare d li q ui d 
f or m ulati o n.
U nla bele d oral d ose of P F -0 7 2 2 0 0 6 0, 1 0 0 m g 
will be a d mi nistere d as a n e xte m p ora ne o usl y 
pre pare d li q ui d f or m ulati o n. A p pr o xi matel y 
2 h o ur s after t he a d mi nistrati o n of t he 
u nla bele d oral d ose, a si n gle d ose of  
μ g 
P F -0 7 2 2 0 0 6 0 c o ntai ni n g 
 n Ci [ 1 4C] 
([1 4C] P F -0 7 2 2 0 0 6 0) w ill be a d mi nistere d I V, 
as a n i nf usi o n o ver a p pr o xi matel y 3 0 mi n utes
Ass oci ate d 
I nter ve nti o n L a bels
[1 4C] P F -0 7 2 2 0 0 6 0
P F -0 7 2 2 0 0 6 0, [ 1 4C] P F -0 7 2 2 0 0 6 0
T his will be a parallel -c o h ort st u d y i ncl u di n g 2 i n de pe n de nt c o h orts wit h o ut cr oss o ver .
C o h ort 2 will be e nr olle d a p pr o xi matel y 1 5 da y s after C o h ort 1 e nr oll me nt. Eli gi ble 
partici pa nts will be a d mitte d t o t he cli nical researc h u nit ( C R U) o n Da y - 1. I n C o h ort 1 , 
partici pa nts will recei ve a si n gle oral d ose of 1 0 0 m g [ 1 4C] P F -0 7 2 2 0 0 6 0 c o ntai ni n g 
a p pr o xi matel y 
n Ci o n Da y  1. Bl o o d , uri ne, feces, a n d v o mit us (if a ny) will be c ollecte d 
o ver pre defi ne d i nter vals . Partici pa nts d ose d i n C o h ort 1 will be eli gible f or disc har ge
bet wee n Da y s 5 t o 1 4 w he n at least o ne of t he 3 f oll o wi n g criteria are met: ( 1) ≥9 0 % of t he 
a d mi nistere d ra di oacti ve d ose has bee n rec o vere d i n uri ne +feces + v o mit us (if a n y); ( 2) < 1 % 
 
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
of t he a d mi nistere d ra di oacti ve d ose has bee n rec o vere d i n uri ne +feces d uri n g 2 4- h o ur
i nter vals o ver 2 c o nsec uti ve da ys, O R ( 3) t he partici pa nt has reac he d Da y 1 4. I n C o h ort 2 , 
partici pa nts will recei ve a si n gle oral 1 0 0 m g d ose of u nla bele d P F -0 7 2 2 0 0 6 0 o n Da y  1. At 
a p pr o xi matel y 2 h o urs after oral d ose, a si n gl e I V d ose of 
µ g ( micr o d ose) 
[1 4C] P F - 0 7 2 2 0 0 6 0 c o ntai ni n g a p pr o xi matel y 
n Ci will be a d mi nistere d as a n i nf usi o n 
o ver 3 0 mi n utes . Bl o o d , uri ne, feces, a n d v o mit us (if a n y) sa m ples will be c ollecte d as per 
detaile d i n t he sc he d ule of acti vities (S o A ) u p u ntil t he disc har ge da y occ urri n g bet wee n 
D a y s 5 t o 1 4. T he d urati o n of c o nfi ne me nt f or C o h ort 2 partici pa nts will e q ual t he l o n gest 
i n di vi d ual partici pa nts d urati o n of c o nfi ne me nt i n C o h ort 1 s o t hat t he d urati o n of uri ne 
sa m ple c ollecti o ns o ver t he peri o ds is c o nsiste nt t o ai d i n acc urate esti mati o n of t he F a.
St atistic al Met h o ds :
A p pr o xi matel y  6 healt h y a d ult male partici pa nts will be e nr olle d i n eac h of t he 2 c o h orts 
base d o n t he i n d ustr y  sta n dar d sa m ple size f or mass bala nce a n d ra di ola bele d micr otracer 
st u dies. T his sa m ple size was n ot c h ose n base d o n a n y e m pirical data or h yp ot hesis testi n g 
criteria.

M ass B al a nce : Perce nt rec o ver y of a d mi nistere d ra di oacti vit y e xcrete d at eac h ti me 
i nter val a n d t otal ra di oacti vit y rec o ver y i n uri ne a n d feces (a dj uste d f or v o mit us , if a n y)
will be re p orte d.

Me a n A bs ol ute
Or al bi o a v ail a bilit y ( F) will be esti mate d as t he rati o of ge o metric 
mea ns of d ose -n or malize d A U C i nf (area u n der t he c o nce ntrati o n-ti me pr ofile fr o m ti me 0 
t o i nfi nit y) f or oral u nla bele d P F- 0 7 2 2 0 0 6 0 vers us I V ra di ola bele d P F -0 7 2 2 0 0 6 0 (fr o m 
C o h ort 2 o nl y ).

Me a n Fr acti o n A bs or be d ( F
a) will ge nerall y  be esti mate d as t he rati o of t otal 
ra di oacti vit y ( d ose n or malize d) e xcrete d i nt o t he uri ne (fr o m ti me 0 t o t he ti me of last 
meas ura ble c o nce ntrati o n ) f oll o wi n g oral a n d I V a d mi nistrati o n of [1 4C] P F -0 7 2 2 0 0 6 0
micr otracer d oses i n C o h ort s 1 a n d 2, res pecti vel y.

Met a b olic Pr ofili n g a n d Met a b olite I de ntific ati o n : Maj or meta b olites of P F- 0 7 2 2 0 0 6 0
i n plas ma, uri ne, a n d feces will be i de ntifie d, if p ossi ble. Res ults of t he meta b olic 
pr ofili n g a nal ys is will be detaile d i n a se parate re p ort a n d will be s u m marize d wit hi n t he 
cli nical st u d y re p ort ( C S R).

S afet y : 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. 
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
P h ar m ac o ki netics A n al ysis

Mass bala nce will be deter mi ne d b y  c u m ulati ve rec o ver y ( %) of ra di oacti vit y i n uri ne, 
feces a n d v o mit us (if a ny).

T he P K c o nce ntrati o n p o p ulati o n is defi ne d as all partici pa nts all ocate d a n d treate d w h o 
ha ve at least 1 P F -0 7 2 2 0 0 6 0 , [1 4C] P F -0 7 2 2 0 0 6 0 , or 1 4C t otal ra di oacti vit y  c o nce ntrati o n
i n t he w h ole treat me nt peri o d.

T he P K para meter a nal ys is p o p ulati o n is defi ne d as all partici pa nts all ocate d a n d treate d 
w h o ha ve at least 1 of t he P F -0 7 2 2 0 0 6 0, [ 1 4C] P F -0 7 2 2 0 0 6 0 , or 1 4C t otal ra di oacti vit y  P K 
para meters of pri mar y  i nterest i n t he w h ole treat me nt peri o d.

P K para meters f or P F -0 7 2 2 0 0 6 0 will be a nal yz e d usi n g sta n dar d n o nc o m part me ntal 
met h o ds of a nal ys is. Act ual P K sa m pli n g ti mes will be used i n t he deri vati o n of 
P F - 0 7 2 2 0 0 6 0 P K para meters w he n a vaila ble, ot her wise n o mi nal ti mes will be use d. 
Et hic al C o nsi der ati o ns:
P F -0 7 2 2 0 0 6 0 will n ot pr o vi de a n y cli nical be nefit t o healt h y partici pa nts i n t his st u d y . T his 
st u d y is desi g ne d pri maril y t o assess h u ma n P K, a bs or pti o n, meta b olis m, a n d eli mi nati o n of 
P F -0 7 2 2 0 0 6 0. Partici pa nts 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 assess me nts. A si n gle 1 0 0 m g oral d ose of P F -0 7 2 2 0 0 6 0
( C o h ort 1), a n d a si n gle 1 0 0 m g oral d ose f oll o we d b y   
μ g I V d ose of P F- 0 7 2 2 0 0 6 0 
( C o h ort 2) are a ntici pate d t o be safe a n d well t olerate 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 partici pa nts, t he p ote ntial ris ks ass ociate d wit h P F - 0 72 2 0 0 6 0 are j ustifie d b y 
t he a ntici pate d be nefits t hat ma y be aff or de d by f urt heri n g t he u n dersta n di n g of 
P F -0 7 2 2 0 0 6 0.
 
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1. 2. Sc he m a
N ot a p plica ble
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ditio n t o t h ose liste d in t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well -bei n g of t he partici pa nt .
T a ble 1 .
Sc he d ule of Acti vit y ( C o h ort 1 -Or al [ 1 4C] -P F -0 7 2 2 0 0 6 0 A d mi nistr ati o n)
Visit I de nti fier
A b bre viati o ns use d i n 
t his ta ble ma y be f o u n d 
i n A p pe n di x 1 0
Scree n a
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n /
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a ys 
(-2 8 t o 
-2)
D a y - 1
D a y 1
D a y 2
D a y 3
D a y 4 D a y 5- 1 4 b D a y 2 9 -
3 6
 
H o urs After Or al 
[1 4C] -P F -0 7 2 2 0 0 6 0 
D ose
-
-
0
0. 5
1
2
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
I nf or me d c onse nt
X
 
 
 
 
 
 
  
  
 
  
  
  
 
 
Re vie w of  eli gi bilit y 
criteria
X  
X 
  
  
  
  
  
  
  
 
  
  
  
  
 
 
I n patie nt sta y at C R U
   
X
 
 
 
 










X b
X
Me dical hist or y
X
X
 
 
 
 
 
 
 
 
 
 
 
D e m o gra p h y c
X
Re vie w dr u g, 
alc o h ol/t o bacc o use d
X  
X 
  
  
  
  
  
  
  
 
  
  
  
   
Xe
X  
X
Re vie w pri or a n d 
c o nc o mita nt 
me dicati o ns
X  
X














X  
X  
X
P h y sical e xa mi nati o nf
X  
X 
  
  
  
  
  
  
  
 
  
  
  
   
Xe
X
S u pi ne 1 2 -lea d 
E C G (si n gle)
X
X 
  
  
  
   
X 
  
 
  
  
  
   
Xe
X
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 1 .
Sc he d ule of Acti vit y ( C o h ort 1 -Or al [ 1 4C] -P F -0 7 2 2 0 0 6 0 A d mi nistr ati o n)
Visit I de nti fier
A b bre viati o ns use d i n 
t his ta ble ma y be f o u n d 
i n A p pe n di x 1 0
Scree n a
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n /
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a ys 
(-2 8 t o 
-2)
D a y - 1
D a y 1
D a y 2
D a y 3
D a y 4 D a y 5- 1 4 b D a y 2 9 -
3 6
 
H o urs After Or al 
[1 4C] -P F -0 7 2 2 0 0 6 0 
D ose
-
-
0
0. 5
1
2
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
S u pi ne vital si g ns 
( bl o o d press ure a n d 
p ulse rate)
X
X 
  
  
  
   
X 
  
 
  
  
  
   
Xe
X
C o ntrace pti o n C hec k g
X
X
X
X
Seri o us a n d n o n -seri o us 
ad verse e ve nt 
m o nit ori n g
X  
X














X  
X  
X
Oral [ 1 4C] -P F -
0 7 2 2 0 0 6 0 
a d mi nistrati o n h
  
   
X 
  
  
  
  
  
  
 
  
  
  
  
 
 
Taste assess me nt i
  
   
Xi
  
  
  
  
  
  
 
  
  
  
  
 
 
E m esis c ollecti o n f or 
ra di oacti vit y 
meas ure me nt, if occ urs j
  
   
X







 

X

X  
X 
 
 
Bl o o d S a m ples 
P K of P F -0 7 2 2 0 0 6 0 
[ L C M S]/ T otal 1 4C 
ra di oacti vit yk
X l
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X b
X
Meta b olite 
i de ntificati o nm
 
X
  X
X  
X 
   
X
  X
X  
X 
   
X 
   
X
  X
X b ,m
X
Cli nical la b orat or y after 
≥4 h o ur fast
X  
X 
  
 
  
  
  
  
  
  
  
 
X
X e
X
Ser ol o g y: H Bs A g, 
H bs A b, H bc A b , 
H C V A b, a n d HI V n
X 
  
  
 
  
  
  
  
  
  
  
  
  
 
  
  
 
 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 0
T a ble 1 .
Sc he d ule of Acti vit y ( C o h ort 1 -Or al [ 1 4C] -P F -0 7 2 2 0 0 6 0 A d mi nistr ati o n)
Visit I de nti fier
A b bre viati o ns use d i n 
t his ta ble ma y be f o u n d 
i n A p pe n di x 1 0
Scree n a
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n /
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a ys 
(-2 8 t o 
-2)
D a y - 1
D a y 1
D a y 2
D a y 3
D a y 4 D a y 5- 1 4 b D a y 2 9 -
3 6
 
H o urs After Or al 
[1 4C] -P F -0 7 2 2 0 0 6 0 
D ose
-
-
0
0. 5
1
2
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
Researc h Sa m ple f or 
P har m ac o ge n o mics o
X o
Uri ne s a m ples f or
Dr u g test p
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C oti ni ne test p
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S p ot c ollecti o n f or 
uri nal ysis (a n d 
micr osc o p y, if nee de d)
X  
X 
  
  
  
  
  
  
  
  
  
   
X 
 
   
Xe
X
P K of P F -0 7 2 2 0 0 6 0 
[ L C M S]/ T otal 1 4C 
ra di oacti vit y/ Meta b olite 
i de ntificati o nq
   
X 
  X







X

X

X  
X  
X
Feces s a m ples f or
T otal 1 4C 
ra di oacti vit y/Meta b olite 
i de ntificati o nr
   
X 
  X









X

X  
X  
X
 
a.
Scree ni n g will be perf or me d wit hi n 2 8 da ys pri or t o t he si n gle oral d ose of P F -0 7 2 2 0 0 6 0.
b.
See Secti o n 4. 1 f or details o n C o h ort 1 disc har ge criteria.
c.
D e m o gra p hics will i ncl u de partici pa nt race, et h nicit y, a ge, ge n der, hei g ht, a n d wei g ht d uri n g t he scree ni n g visit.
d.
T he re vie w  of dr u g, alc o h ol/t o bacc o use ma y i ncl u de a n alc o h ol breat h test or uri ne alc o h ol test or bl o o d alc o h ol test (at discreti o n of i n vesti gat or), w hic h 
will be perf or me d at scree ni n g, o n Da y - 1 a n d at disc har ge. T hese tests ma y be perf or me d at a n y ot her ti me at t he discreti o n of t he i n vesti gat or. 
e.
Pr oce d ures t o be perf or me d o nl y o n t he da y of d isc har ge or Da y 1 4. N o E C G or vital si g ns will be c ollecte d o n Da y  1 4. (see als o Secti o n 4. 1 ).
f.
C o m plete p h ysical e xa m i ncl u di n g hei g ht a n d wei g ht will be perf or me d b y trai ne d me dical pers o n nel at t he C R U at scree ni n g or Da y -1 o nl y. A brief 
p h ysical e xa mi nati o n ma y be perf or me d pri or t o disc har ge fr o m t he C R U a n d at ot her desi g nate d ti me p oi nts at t he discreti o n o f t he i n vesti gat or.
g.
T he i n vesti gat or or his/ her desi g nee will disc uss wit h t he partici pa nt t he nee d t o use hi g hl y effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectl y acc or di n g t o 
c o ntrace pti o n g ui deli nes. 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 1 .
Sc he d ule of Acti vit y ( C o h ort 1 -Or al [ 1 4C] -P F -0 7 2 2 0 0 6 0 A d mi nistr ati o n)
Visit I de nti fier
A b bre viati o ns use d i n 
t his ta ble ma y be f o u n d 
i n A p pe n di x 1 0
Scree n a
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n /
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a ys 
(-2 8 t o 
-2)
D a y - 1
D a y 1
D a y 2
D a y 3
D a y 4 D a y 5- 1 4 b D a y 2 9 -
3 6
 
H o urs After Or al 
[1 4C] -P F -0 7 2 2 0 0 6 0 
D ose
-
-
0
0. 5
1
2
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
h.
P F -0 7 2 2 0 0 6 0 w ill be a d mi nistere d orall y after o ver ni g ht fasti n g of at least 1 0 h o urs o n Da y 1. 
i.
Q uesti o n naire t o be c o m plete d b y partici pa nts as s o o n as practicall y p ossi ble ( wit hi n   1 mi n) after c o m pleti o n of d osi n g, pl us at 5   mi n, 1 0  mi n, a n d 2 0  mi n 
p ost d ose. P K sa m ples will ta ke t he pri orit y w he n t he 2 pr oce d ures c o nflict.
j.
V o m it us sa m ples will be c ollecte d as descri be d i n Secti o n 8. 5. 3 .
k.
Bl o o d sa m ples will be c ollecte d at pre d ose ( wit hi n a p pr o xi matel y 1 h o ur pri or t o P F -0 7 2 2 0 0 6 0 d osi n g) a n d at p ost -d ose ti me p oi nts i n dicate d i n t he ta ble u p 
t o disc har ge. If E C G a n d bl o o d press ure/ p ulse rate assess me nts are sc he d ule d at t he sa me no m i nal ti me p oi nt as a P K sa m ple, P K sa m ples s h o ul d be 
c ollecte d after c o m pleti o n of t hese assess me nts , wit h bl o o d sa m pli n g f or P K as cl ose as p ossi ble t o t he pla n ne d ti me p oi nt. Bl o o d sa m ples will be pr ocesse d 
t o plas ma as per i nstr ucti o ns of t he la b ma n ual. (See als o Secti o n 8. 5. 1 ).
l.
T his 8 m L scree ni n g sa m ple c ollecti o n will n ot be use d t o a nal yze t he c ol d P F -0 7 2 2 0 0 6 0 b ut will be use d t o assess 1 4C t otal ra di oacti vit y f or scree ni n g a n d 
be st ore d f or p ote ntial use as t he dil ue nt f or p ost -d ose A M S sa m ples.
m.
Bl o o d sa m ples (a p pr o xi matel y 1 0 m L) will be c ollecte d at pre d ose ( w it hi n a p pr o xi matel y 1 h o ur pri or t o P F -0 7 2 2 0 0 6 0 d osi n g) a n d at 0. 5, 1, 2, 4, 6, 8, 1 2, 
2 4, 4 8, 7 2, 9 6, a n d 1 4 4 (if still i n C R U) h o urs p ost -d os e. If E C G a n d bl o o d press ure/ p ulse rate assess me nts are sc he d ule d at t he sa me n o mi nal ti me p oi nt as 
t hese sa m ples, t hese sa m ples s h o ul d be c ollecte d after c o m pleti o n of t hese assess me nts, wit h bl o o d sa m pli n g f or P K as cl ose as p ossi ble t o t he pla n ne d 
ti me poi nt . Bl o o d sa m ples will be pr ocesse d t o plas ma as per i nstr ucti o ns of t he la b ma n ual. ( See als o Secti o n 8. 5. 1 ).
n.
H bs A b will be teste d if H bs A g a n d/ or H bc A b are p ositi ve.
o.
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.
p.
Uri ne dr u g a n d uri ne c oti ni ne ( ma n dat or y) a n d alc o h ol breat h test or uri ne alc o h ol test or bl o o d alc o h ol test (at discreti o n of i n vesti gat or) will be perf or me d 
at scree ni n g, o n Da y -1. T hese tests ma y be perf or me d at a n y ot her ti me at t he discreti o n of t he i n vesti gat or.
q.
“Bla n k” pre d ose uri ne sa m ple t o be c ollecte d w it hi n 2 4 h pri or t o d osi n g a n d at i nter vals of 0 -1 2 h, 1 2 -2 4 h p ost oral d ose, a n d at eac h s u bse q ue nt 2 4 h i nter val 
u p t o disc har ge . F orce d v oi d i nt o t he c ollecti o n c o ntai ner at t he e n d of t he c ollecti o n peri o d. (see als o Secti o n 8. 5. 2 ).
r.
“ Bla n k” fecal sa m ple t o be c ollecte d at baseli ne fr o m at least 1 b o w el mo ve me nt d uri n g t he 4 8 h pre d ose i nter val, w hic h ma y be c ollecte d fr o m h o me. T he 
last c ollecte d fecal sa m ple will be use d as t he pre-d ose sa m ple a n d all pre vi o us pre -d ose sa m ples will be destr o ye d. Fecal sa m ples will als o be c ollecte d at 
i nter vals of 0-2 4 h p ost oral d ose, a n d at eac h s u bse q ue nt 2 4 h i nter val u p t o disc har ge . (see als o Secti o n 8. 5. 2 ).
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 2 .
Sc he d ule of Acti vit y ( C o h ort 2 -Or al u nl a bele d P F -0 7 2 2 0 0 6 0 a n d I V [1 4C]- P F -0 7 2 2 0 0 6 0 a d mi nistr ati o n)
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble ma y be 
f o u n d i n A p pe n di x 1 0
Scree n a
 
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n/
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a y (-
2 8 t o -
2)
D a y - 1
D a y 1
D a y 2 D a y 3 D a y 4 D a y 5-
1 4 b
D a y 
2 9 -3 6
 
H o urs Rel ati ve t o Or al D osi n g of 
U nl a bele d P F -0 7 2 2 0 0 6 0
-
-
0 0. 5
1
2
2. 5 2. 7 5
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
H o urs Rel ati ve t o D osi n g of [1 4C]- P F -
0 7 2 2 0 0 6 0 (I V  i nf usi o n st art)
0
0. 5 0. 7 5
1
2
4
6
1 0
1 4
2 2
3 4
4 6
7 0
9 4 - 3 1 0
-
I nf or me d c o nse nt
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Re vie w of  eli gi bilit y criteria
X  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
I n patie nt sta y at C R U
   
X



X b
X
Me dical hist or y
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D e m o gra p h y c
X
Re vie w dr u g, alc o h ol/t o bacc o use d
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X e
X
X
Re vie w pri or a n d c o nc o mita nt 
me dicati o ns
X  
X



X  
X  
X
P h y sical e xa mi nati o nf
X  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
   
X e
X
S u pi ne 1 2 -lea d E C G (si n gle)
X
X
 
 
 
 
 
X
 
 
 
 
 
 
 
 
X e
X
S u pi ne vital si g ns ( bl o o d press ure a n d 
p ulse rate)
X  
X   
  
  
  
   
X   
  
  
  
  
  
  
   
X e
X
C o ntrace pti o n C hec k g
X
X
X
X
Seri o us a n d n o n -seri o us a d verse e ve nt 
m o nit ori n g
X  
X



X  
X  
X
Oral U nla bele d P F -0 7 2 2 0 0 6 0 
a d mi nistrati o n h
  
   
X   
  
  
  
  
  
  
  
  
  
  
  
  
 
 
I V i nf usi o n of [1 4C ]-P F -0 7 2 2 0 0 6 0
X i
Taste assess me nt j
  
   
Xh
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
E m esis c ollecti o n f or ra di oacti vit y 
meas ure me nt, if occ urs k
  
   
X X

X  
X 
 
 
Bl o o d S a m ples f or
P K of P F -0 7 2 2 0 0 6 0 [ L C M S] l
  X X
X  
X
X
X
X
X
X  
X  
X  
X  
X  
X  
X
X
P K of [ 1 4C] P F -0 7 2 2 0 0 6 0 m
  X 
  
  
   
X  
X   
X  
X
X
X
X
X  
X  
X  
X  
X  
X   
X
X
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 2 .
Sc he d ule of Acti vit y ( C o h ort 2 -Or al u nl a bele d P F -0 7 2 2 0 0 6 0 a n d I V [1 4C]- P F -0 7 2 2 0 0 6 0 a d mi nistr ati o n)
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble ma y be 
f o u n d i n A p pe n di x 1 0
Scree n a
 
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n/
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a y (-
2 8 t o -
2)
D a y - 1
D a y 1
D a y 2 D a y 3 D a y 4 D a y 5-
1 4 b
D a y 
2 9 -3 6
 
H o urs Rel ati ve t o Or al D osi n g of 
U nl a bele d P F -0 7 2 2 0 0 6 0
-
-
0 0. 5
1
2
2. 5 2. 7 5
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
H o urs Rel ati ve t o D osi n g of [1 4C]- P F -
0 7 2 2 0 0 6 0 (I V  i nf usi o n st art)
0
0. 5 0. 7 5
1
2
4
6
1 0
1 4
2 2
3 4
4 6
7 0
9 4 - 3 1 0
-
Meta b olite i de ntificati o n
   
X   X X   
X 
   
X
X
X
X 
   
X  
X  
X  
X b ,n
Cli nical la b orat or y after ≥4 h o ur fast
X  
X 
  
  
  
  
 
X  
X e
X
Ser ol o g y: H Bs A g, H Bs A b, H Bc A b, 
H C V A b, a n d HI V o
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
Researc h Sa m ple f or 
P har m c o ge n o mics p
X p
Uri ne s a m ples f or
Dr u g test q
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C oti ni ne test q
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S p ot c ollecti o n f or uri nal ysis (a n d 
micr osc o p y, if nee de d)
X  
X 
  
  
  
  
  
  
  
  
  
   
X 
  
   
X e
X
T otal 1 4C ra di oacti vit y/ Meta b olite 
i de ntificati o nr
   
X 
   
X
X
X

X  
X 
X
Feces s a m ples f or
T otal 1 4C ra di oacti vit y/ Meta b olite 
i de ntificati o ns
   
X 
   
X
X

X  
X 
X
 
a.
Scree ni n g will be perf or me d wit hi n 2 8 da ys pri or t o t he si n gle oral d ose of P F -0 7 2 2 0 0 6 0.
b.
See Secti o n 4. 1 f or details o n C o h ort 2 disc har ge criteria.
c.
D e m o gra p hics will i ncl u de partici pa nt race, et h nicit y, a ge, ge n der, hei g ht, a n d wei g ht d uri n g t he scree ni n g visit.
d.
T he re vie w  of dr u g, alc o h ol/t o bacc o use ma y i ncl u de a n alc o h ol breat h test or uri ne alc o h ol test or bl o o d alc o h ol test (at discreti o n of i n vesti gat or), w hic h 
will be perf or me d at scree ni n g, o n Da y - 1 a n d at disc har ge . T hese tests ma y be perf or me d at a n y ot her ti me at t he discreti o n of t he i n vesti gat or.
e.
Pr oce d ures t o be perf or me d o nl y o n t he da y of disc har ge or Da y 1 4. N o E C G or vital si g ns will be c ollecte d o n Da y   1 4. (see als o Secti o n 4. 1 ).
f.
C o m plete p h ysical e xa m i ncl u di n g hei g ht a n d wei g ht will be perf or me d b y trai ne d me dical pers o n nel at t he C R U at scree ni n g or Da y -1 o nl y. A brief 
p h ysical e xa mi nati o n ma y be perf or me d pri or t o disc har ge fr o m t he C R U a n d at ot her desi g nate d ti me p oi nts at t he discreti o n of t he i n vesti gat or .
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 2 .
Sc he d ule of Acti vit y ( C o h ort 2 -Or al u nl a bele d P F -0 7 2 2 0 0 6 0 a n d I V [1 4C]- P F -0 7 2 2 0 0 6 0 a d mi nistr ati o n)
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble ma y be 
f o u n d i n A p pe n di x 1 0
Scree n a
 
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n/
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a y (-
2 8 t o -
2)
D a y - 1
D a y 1
D a y 2 D a y 3 D a y 4 D a y 5-
1 4 b
D a y 
2 9 -3 6
 
H o urs Rel ati ve t o Or al D osi n g of 
U nl a bele d P F -0 7 2 2 0 0 6 0
-
-
0 0. 5
1
2
2. 5 2. 7 5
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
H o urs Rel ati ve t o D osi n g of [1 4C]- P F -
0 7 2 2 0 0 6 0 (I V  i nf usi o n st art)
0
0. 5 0. 7 5
1
2
4
6
1 0
1 4
2 2
3 4
4 6
7 0
9 4 - 3 1 0
-
g.
T he i n vesti gat or or his/ her desi g nee will disc uss wit h t he partici pa nt t he nee d t o use hi g hl y effecti ve c o ntrace pti o n c o nsist e ntl y a n d c or rectl y acc or di n g t o 
c o ntrace pti o n g ui deli nes.
h.
P F -0 7 2 2 0 0 6 0 w ill be a d mi nistere d orall y after o ver ni g ht fasti n g of at least 1 0 h o urs o n Da y 1.
i.
I V [1 4C] P F -0 7 2 2 0 0 6 0 d ose t o be a d mi nistere d as a n i nf usi o n o ver a p pr o xi matel y 3 0 mi n utes (starti n g at a p pr o xi matel y 2 h o ur after t he a d mi nistrati o n of t he 
oral u nla bele d P F -0 7 2 2 0 0 6 0 d ose ).
j.
Q uesti o n naire t o be c o m plete d b y partici pa nts as s o o n as practicall y p ossi ble ( wit hi n   1 mi n) after c o m pleti o n of d osi n g, pl us at 5   mi n, 1 0  mi n, a n d 2 0  mi n 
p ost d ose. P K sa m ples will ta ke t he pri orit y if t he 2 pr oce d ures start t o c o nflict.
k.
V o m it us sa m ples will be c ollecte d as descri be d i n Secti o n 8. 5. 3 .
l.
Bl o o d sa m ples ( a p pr o xi matel y 4 m L) will be c ollecte d at pre d ose ( wit hi n a p pr o xi matel y 1 h o ur pri or t o P F-0 7 2 2 0 0 6 0 d osi n g) a n d at p ost -d ose ti me p oi nts 
i n dicate d i n t he ta ble u p t o disc har ge . If E C G a n d bl o o d press ure/ p ulse rate assess me nts are sc he d ule d at t he sa me n o mi nal ti me p oi nt as a P K sa m ple, P K 
sa m ples s h o ul d be c ollecte d after c o m pleti o n of t hese assess me nts , wit h bl o o d sa m pli n g f or P K as cl ose as p ossi ble t o t he pla n ne d ti me p oi nt . Bl o o d sa m ples 
will be pr ocesse d t o plas ma as per i nstr ucti o ns of t he la b ma n ual. ( See als o Secti o n 8. 5. 1 ).
m.
A 8 m L scree ni n g sa m ple c ollecti o n will be use d t o assess [ 1 4C] P F -0 7 2 2 0 0 6 0 f or scree ni n g o nl y a n d will be st ore d f or p ote ntial use as t he dil ue nt f or p ost -
d ose A M S sa m ples . Bl o o d sa m ples (a p pr o xi matel y 4 m L) will be c ollecte d at prei nf usi o n ( wit hi n a p pr o xi matel y 1 5 m i n pri or t o [1 4C] P F -0 7 2 2 0 0 6 0 i nf usi o n) 
a n d at p ost-i nf usi o n ti me p oi nts i n dicate d i n t he ta ble u p t o disc har ge. If E C G a n d bl o o d press ure/ p ulse rate assess me nts are sc he d ule d at t he sa me n o mi nal 
ti me p oi nt as a P K sa m ple, P K sa m ples s h o ul d be c ollecte d after c o m pleti o n of t hese assess me nts , wit h bl o o d sa m pli n g f or P K as cl ose as p ossi ble t o t he 
pla n ne d ti me p oi nt . Bl o o d sa m ples w ill be pr ocesse d t o plas ma as per i nstr ucti o ns of t he la b ma n ual. ( See als o Secti o n 8 . 5. 1).
n.
C o h ort 2 bl o o d sa m ples ( a p pr o xi matel y 1 0 m L) f or c o nti ge nt use will be c ollecte d at pre d ose ( wit hi n a p pr o xi matel y 1 h o ur pri or t o P F -0 7 2 2 0 0 6 0 d osi n g) 
a n d at 0. 5, 1, 2, 4, 6, 8, 1 2, 2 4, 4 8, 7 2, 9 6, a n d 1 4 4 (if still i n C R U) h o urs p ost -d ose. If E C G a n d bl o o d press ure/ p ulse rate assess me nts are sc he d ule d at t he 
sa me n o mi nal ti me p oi nt as t hese sa m ples, t hese sa m ples s h o ul d be c ollecte d after c o m pleti o n of t hese assess me nts wit h bl o o d sa m pli n g f or P K as cl ose as 
p ossi ble t o t he pla n ne d ti me p oi nt . Bl o o d sa m ples will be pr ocesse d t o plas ma as per i nstr ucti o ns of t he la b ma n ual. ( See als o Secti o n 8. 5. 1 ).
o.
H Bs A b will be teste d if H Bs A g a n d/ or H Bc A b are p ositi ve.
p.
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.
q.
Uri ne dr u g a n d uri ne c oti ni ne ( ma n dat or y) a n d alc o h ol breat h test (at discreti o n of i n vesti gat or) w ill be perf or me d at scree ni n g, o n Da y -1. T hese tests ma y 
be perf or me d at a n y ot her ti me at t he discreti o n of t he i n vesti gat or.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 5
T a ble 2 .
Sc he d ule of Acti vit y ( C o h ort 2 -Or al u nl a bele d P F -0 7 2 2 0 0 6 0 a n d I V [1 4C]- P F -0 7 2 2 0 0 6 0 a d mi nistr ati o n)
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble ma y be 
f o u n d i n A p pe n di x 1 0
Scree n a
 
St u d y Peri o d
F U 
p h o ne 
c all
E arl y 
Ter mi n ati o n/
Disc o nti n u ati o n
D a ys rel ati ve t o D a y 1
D a y (-
2 8 t o -
2)
D a y - 1
D a y 1
D a y 2 D a y 3 D a y 4 D a y 5-
1 4 b
D a y 
2 9 -3 6
 
H o urs Rel ati ve t o Or al D osi n g of 
U nl a bele d P F -0 7 2 2 0 0 6 0
-
-
0 0. 5
1
2
2. 5 2. 7 5
3
4
6
8
1 2
1 6
2 4
3 6
4 8
7 2
9 6 - 3 1 2
-
-
H o urs Rel ati ve t o D osi n g of [1 4C]- P F -
0 7 2 2 0 0 6 0 (I V  i nf usi o n st art)
0
0. 5 0. 7 5
1
2
4
6
1 0
1 4
2 2
3 4
4 6
7 0
9 4 - 3 1 0
-
r.
“Bla n k” pre d ose uri ne sa m ple t o be c ollecte d w it hi n 2 4 h pri or t o d osi n g a n d at i nter vals of 2- 1 2 h, 1 2 -2 4 h p ost oral d ose, a n d at eac h s u bse q ue nt 2 4 h i nter val 
u p t o disc har ge. F orce d v oi d i nt o t he c ollecti o n c o ntai ner at t he e n d of t he c ollecti o n peri o d. (see als o Secti o n 8. 5. 2 ).
s.
“ Bla n k” fecal sa m ple t o be c ollecte d at baseli ne fr o m at least 1 b o w el mo ve me nt d uri n g t he 4 8 h pre d ose i nter val, w hic h ma y be c ollecte d fr o m h o me. T he 
last c ollecte d fecal sa m ple will be use d as t he pre-d ose sa m ple a n d all pre vi o us pre -d ose sa m ples will be destr o ye d. Fecal sa m ples will als o be c ollecte d at 
i nter vals of 2 -2 4 h p ost oral d ose, a n d at eac h s u bse q ue nt 2 4 h i nter val u p t o disc har ge. (see als o Secti o n 8. 5. 2 ).
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. I N T R O D U C TI O N
P F -0 7 2 2 0 0 6 0 is a selecti ve C D K 4 i n hi bit or t hat is c urre ntl y bei n g i n vesti gate d i n P hase 1 
st u dies ( C 4 3 9 1 0 0 1 a n d C 4 3 9 1 0 0 2) i n partici pa nts wit h metastatic or a d va nce d s oli d t u m ors.
2. 1. St u d y R ati o n ale 
T he p ur p ose of t he st u d y  will be t o i n vesti gate t he meta b olis m a n d e xcreti o n f oll o wi n g a 
si n gle oral a d mi nistrati o n of [1 4C]- P F - 0 7 2 2 0 0 6 0 u n der faste d c o n diti o n i n healt h y  male 
partici pa nt s. T he data ge nerate d fr o m t his st u d y will be use d t o assess t he cleara nce 
mec ha nis ms f or P F -0 7 2 2 0 0 6 0 as well as i de ntif y meta b olites t hat s h o ul d be q ualifie d t o 
a d here t o t he I CH ( M 3) R 2 g ui da nce. I n a d diti o n, t his st u d y  will c haracterize t he fracti o n of 
d ose a bs or be d a n d bi oa vaila bilit y of orall y a d mi nistere d P F- 0 7 2 2 0 0 6 0 u n der t he faste d 
c o n diti o n , i n refere nce t o a n I V i nf usi o n of [ 1 4C] P F - 0 7 2 2 0 0 6 0 ( gi ve n as a micr otracer 
micr o d ose i nf usi o n f oll o wi n g a d mi nistrati o n of a n oral u nla belle d d ose ), a n d will als o assess 
P K para meters of P F -0 7 2 2 0 0 6 0 f oll o wi n g b ot h oral a n d I V a d mi nistrati o n of 
[1 4C] P F - 0 7 2 2 0 0 6 0.
T his st u d y  will als o e val uate se ns or y a n d taste attri b utes (e g, bitter ness a n d t o n g ue/ m o ut h 
se nsati o n) of t he P F-0 7 2 2 0 0 6 0 oral s us pe nsi o n t o g ui de t he de vel o p me nt of p e diatric-frie n dly 
f or m ulati o ns. 
2. 2. B ac k gr o u n d 
P F -0 7 2 2 0 0 6 0 is a selecti ve C D K 4 i n hi bit or t hat is c urre ntly bei n g i n vesti gate d i n partici pa nts 
wit h metastatic or a d va nce d s oli d t u m ors. P F- 0 7 2 2 0 0 6 0 differs fr o m c urre ntl y  a p pr o ve d d ual 
C D K 4/ 6 i n hi bit ors i n t hat it dis pla y s greater C D K 4-o ver -C D K 6 selecti vit y  a n d is t heref ore 
h y p ot hesize d t o dri ve t u m or gr o wt h i n hi biti o n t hr o u g h greater C D K 4 selecti vit y, w hile 
mi ni mizi n g C D K 6 dri ve n he mat o p oietic e ffects. T his ma y tra nslate t o i m pr o ve d efficac y a n d 
t olera bilit y o ver ot her C D K 4/ 6 i n hi bit ors. T he n o ncli nical P K/t o xic o ki netic, A D M E 
pr o perties of P F - 0 72 2 0 0 6 0 ha ve bee n e val uate d i n vitr o a n d i n vi v o t o s u p p ort n o ncli nical 
safety e val uati o ns a n d t o assess t he p ote ntial rele va nce t o h u ma ns. T he oral P K of 
P F -0 7 2 2 0 0 6 0 i n n o ncli nical s pecies i n dicate d
oral bi oa vaila bilit y . T he
meta b olic pat h wa y s of P F - 0 7 2 0 0 6 0 i n vitr o a n d i n vi v o i ncl u de d gl uc ur o ni dati o n me diate d 
b y  U G T 2 B 7 a n d o xi dati o n me diate d b y C Y P 3 A 4 . Meta b olites were f o u n d c o nsiste nt 
bet wee n h u ma n i n vitr o s y ste m a n d ot her e val uate d t o xic ol o g y s pecies ( b ot h i n vitr o a n d i n 
vi v o matrices). R e nal e xcreti o n of P F - 0 7 2 2 0 0 6 0 was
 i n rats a n d d o gs. 
T he c urre nt st u d y  will i n vesti gate t he a bs or pti o n, meta b olis m a n d e xcreti o n of 
[1 4C]- P F - 0 7 2 2 0 0 6 0 as well as t he a bs ol ute bi oa vaila bilit y a n d fracti o n a bs or be d of 
P F - 0 7 2 2 0 0 6 0 usi n g micr otracer a p pr oac h i n healt h y male partici pa nts.
2. 2. 1. N o ncli nic al P h ar m ac ol o g y
Details of t he n o ncli nical p har mac ol o g y  of P F-0 7 2 2 0 0 6 0 ca n be f o u n d i n t he c urre nt I B.
 
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 2. 2. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
F oll o wi n g I V d osi n g i n m o use, rat, a n d d o g, P F-0 7 2 2 0 0 6 0 de m o nstrate d 
t o
plas ma C L  (
%-
% of he patic bl o o d fl o w), 
 Vss ( 
t o 
 L/ k g), a n d t½ val ues 
ra n gi n g fr o m  
t o 
 h o urs. Si n gle-d ose P K st u dies wit h P F -0 7 2 2 0 0 6 0 i n t hese s pecies 
i n dicate d P F-0 7 2 2 0 0 6 0 ha d 
oral bi oa vaila bilit y  ( %F i n t he ra n ge of  
-
%). I n 
1- m o nt h t o xicit y  st u dies, s yste mic e x p os ure ( C ma x a n d A U C 2 4) of P F-0 7 2 2 0 0 6 0
 a n d
 was o bser ve d i n rats a n d d o gs. 
P F -0 7 2 2 0 0 6 0 ha d
 plas ma pr otei n bi n di n g (f u ra n gi n g fr o m 
-
; 
 i n 
h u ma n plas ma) a n d t here was
of P F -0 7 2 2 0 0 6 0 i nt o 
 i n all e val uate d s pecies ( m o use, rat, d o g, a n d h u ma n).
I n vitr o a n d i n vi v o (after oral a d mi nistrati o n), t he
meta b oli c pat h wa ys of 
P F - 0 7 2 2 0 0 6 0 were gl uc ur o ni dati o n a n d o xi dati o n. T he meta b olite pr ofile o bser ve d i n h u ma n 
he pat oc y tes was  
t hat i n m o use, rat, a n d m o n ke y he pat oc ytes; t here were 
 
 t hat were 
 h u ma n. T he  
meta b olis m pat h wa ys o bser ve d i n h u ma n 
he pat oc y tes
 i n t he plas ma of t he rat a n d d o g t o xic ol o g y s pecies. I n vitr o 
st u dies i n dicate d t he meta b olis m of P F- 0 7 2 2 0 0 6 0 was
 U G T-me diate d (
%) wit h 
t he  
meta b olis m via C Y P 3 A 4  
%); i n a d diti o n, U G T 2B 7 was t he 
 e nz y me 
i n v ol ve d i n t he f or mati o n of t he 
P F- 0 7 2 2 0 0 6 0 gl uc ur o ni de meta b olite. Re nal e xcreti o n 
of P F -0 7 2 2 0 0 6 0 was 
i n rats a n d d o gs. I n vitr o st u dies i n dicate P F -0 7 2 2 0 0 6 0 t o be a 
s u bstrate of 
 a n d 
P F - 0 7 2 2 00 6 0 has t he p ote ntial f or 
of  
i n t he g ut a n d li ver a n d t o  
 
 at t he rele va nt 
cli nical e x p os ures of 
a n d 3 0 0 m g BI D. P F -0 7 2 2 0 0 6 0 als o has t he p ote ntial f or 
of 
 i n t he g ut a n d li ver at t he rele va nt cli nical e x p os ures of 3 0 0 m g BI D. 
Treat me nt wit h P F - 0 7 2 2 0 0 6 0 
i n d uce d 
 i n 
cr y o preser ve d h u ma n he pat oc y tes. Treat me nt wit h P F- 0 7 2 2 0 0 6 0 
or 
at t he
or
 i n h u ma n he pat oc ytes. I n d ucti o n of 
 
 si nce it
 It is t h us
t hat P F-0 7 2 2 0 0 6 0 will
A d diti o nal i nf or mati o n o n t he n o ncli nical P K a n d meta b olis m of P F- 0 7 2 2 0 0 6 0 is a vaila ble i n 
t he c urre nt I B.
2. 2. 3. N o ncli nic al S afet y
T he t o xicit y  pr ofile of P F-0 7 2 2 0 0 6 0 was assesse d i n e x pl orat or y  a n d 1-m o nt h pi v otal G L P 
t o xicit y st u dies i n rats a n d d o gs.
 
 res pecti vel y. T he pri mar y 
tar get or ga ns i de ntifie d were
 
 
0
 
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
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
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
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 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
P F -0 7 2 2 0 0 6 0 was assesse d i n a series of ge netic t o x icit y assa ys. All i n vitr o tests were 
c o n d ucte d wit h a n d wit h o ut e x o ge n o us meta b olic acti vati o n usi n g c o nce ntrati o ns u p t o t h ose 
li mite d b y c yt ot o xicit y, i ns ol u bilit y, or t he acce pta ble li mits of t he test s yste m. P F-0 7 2 2 0 0 6 0 
was ne gati ve f or m uta ge nicit y  in b ot h t he prese nce a n d a bse nce of meta b olic acti vati o n i n t he 
G L P micr o bial re verse m utati o n assa y s. A d diti o nall y, P F- 0 7 2 2 0 0 6 0 was ne gati ve i n t he 
e x pl orat or y i n vitr o micr o n ucle us assa y i n T K 6 cells u n der all test c o n diti o ns. In t he G L P i n 
vi v o micr o n ucl e us assess me nt, P F -0 7 2 2 0 0 6 0 di d n ot i n d uce str uct ural c hr o m os o me 
a berrati o ns or p ol ypl oi d y i n n ucleate d cells fr o m t he b o ne marr o w of male a n d fe male rats at 
m g/ k g/ da y , a n d was t heref ore, n ot c o nsi dere d clast o ge nic i n t hat assa y. 
H o we ve r, P F-0 7 2 2 0 0 6 0 i n d uce d s mall b ut statisticall y  si g nifica nt i ncreases i n micr o n ucle us 
f or mati o n i n p ol yc hr o matic er yt hr oc ytes fr o m b o ne marr o w i n male rats ≥ 
m g/ k g/ da y  a n d 
i n fe male rats at  
m g/ k g/ da y. P F-0 7 2 2 0 0 6 0 is n o n -m uta ge nic ( ne gati ve i n A mes) a n d n o n -
clast o ge nic ( ne gati ve i n c hr o m os o me a berrati o n), P F -0 7 2 2 0 0 6 0 p os es n o ge n ot o xicit y  ris k 
f or si n gle-d ose lifeti me e x peri me ntati o n i n healt h y  Partici pa nt s.
P F -0 7 2 2 0 0 6 0 ha d mi ni mal acti vit y  i n sec o n dar y p har mac ol o g y a n d e x vi v o safety 
p har mac ol o g y  assa ys, i ncl u di n g wea k acti vit y (IC 5 0 >
µ M) t o war d t he h E R G c ha n nel. 
N o car di o vasc ular effects ( E C G or hist o pat h ol o g y ) were o bser ve d u p t o t he hi g hest d ose 
teste d (  
m g/ k g/ da y) i n t he pi v otal d o g st u d y. I n a c o nsci o us-tele metere d d o g G L P st u d y, 
m g / k g/ da y pr o d uce d a n
o nl y after t he sec o n d d ose; n o effects were see n after t he first d ose. Relati ve t o 
t he Cma x at t he h u ma n d ose of 1 0 0 m g, t he N O E L f or car di o vasc ular effect is 
x.
I n a G L P ne ur o p ul m o nar y safety st u d y i n rats, P F -0 7 2 2 0 0 6 0 a d mi nistrati o n di d n ot res ult i n 
a n y ne ur of u ncti o nal or p ul m o nar y effects u p t o t he hi g hest d ose teste d. Relati ve t o t he Cma x at 
t he h u ma n d ose of 1 0 0 m g, t he N O E L f or ne ur o p ul m o nar y  safety is
× .
A d diti o nal i nf or mati o n of t he n o ncli nical safet y of P F - 0 7 2 2 0 0 6 0 is a vaila ble i n t he c urre nt 
I B.
2. 2. 4. Cli nic al O ver vie w
P F -0 7 2 2 0 6 0 0 is bei n g e val uate d as a si n gle a ge nt a n d i n c o m bi nati o n wit h E T i n st u d y  
C 4 3 9 1 0 0 1 a n d i n c o m bi nati o n wit h P F - 0 7 1 0 4 0 9 1 (a selecti ve C D K 2 i n hi bit or) i n st u d y 
C 4 3 9 1 0 0 2. I ncl u de d i n t his secti o n are s u m maries of t he i nteri m res ults of t he 2 o n g oi n g 
st u dies.
St u d y  C 4 3 9 1 0 0 1 is a P hase 1/ 1 b st u d y of P F-0 7 2 2 0 0 6 0 i n partici pa nts wit h a d va nce d s oli d 
t u m ors wit h t he p ur p ose of e valuati n g safet y, t olera bilit y , P K, P D a n d a nti-t u m or acti vit y of 
P F -0 7 2 2 0 0 6 0 as a si n gle a ge nt a n d i n c o m bi nati o n wit h E T. St u d y  C 4 3 9 1 0 0 2 is a P hase 1 b / 2 
st u d y of P F-0 7 2 2 0 0 6 0 a n d P F -0 7 1 0 4 0 9 1 i n partici pa nts wit h m B C or ot her a d va nce d s oli d 
t u m ors a n d i n c o m bi nati o n wit h E T (tri plet c o m bi nati o ns) i n partici pa nts wit h 
metastatic/a d va nce d m B C t o e val uate t he safet y, t olera bilit y, P K, P D, a n d a ntit u m or acti vit y 
of P F -0 7 2 2 0 0 6 0 a n d P F - 0 7 1 0 4 0 9 1 c o m bi nati o n.
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 2. 4. 1. S afet y O ver vie w
As of t he data c ut -off date of 0 2 Se pte m be r 2 0 2 2 f or C 4 3 9 1 0 0 1, a t otal of 6 6 partici pa nts 
ha ve bee n treate d wit h P F- 0 7 2 2 0 0 6 0; 3 4 partici pa nts ha ve bee n treate d wit h 1 0 0, 2 0 0, 3 0 0, 
4 0 0, a n d 5 0 0 m g BI D si n gle a ge nt P F - 0 7 2 2 0 0 6 0. T hirtee n partici pa nts ha ve bee n treate d 
wit h 3 0 0 m g BI D, a n d 4 0 0 m g BI D P F - 0 7 2 2 0 0 6 0 i n c o m bi nati o n wit h letr oz ole. T hirtee n 
partici pa nts ha ve bee n treate d wit h 3 0 0 m g BI D a n d 4 0 0 m g BI D P F -0 7 2 2 0 0 6 0 i n 
c o m bi nati o n wit h f ul vestra nt. Si x partici pa nts ha ve bee n treate d wit h 4 0 0 m g BI D si n gle 
a ge nt P F- 0 7 2 2 0 0 6 0 wit h f o o d. F or t he C 43 9 1 0 0 1 st u d y , t he m o n ot hera p y M T D f or P F-
0 7 2 2 0 0 6 0 was deter mi ne d t o be 4 0 0   m g BI D. T he R D E f or m o n ot hera py was deter mi ne d t o 
be 3 0 0 m g BI D.
As of 0 2 Se pte m ber 2 0 2 2 f or C 4 3 9 1 0 0 1, 5 9 ( 8 9. 4 %) partici pa nts re p orte d a t otal of 3 7 5 all-
ca usalit y T E A Es. T we nt y-three partici pa nts re p orte d all -ca usalit y Gra de 3 ( 2 2 [ 3 3. 3 %]) or 4 
( 1 [ 1. 5 %]) T E A Es a n d 1 ( 1. 5 %) partici pa nt e x perie nce d Gra de 5 all-ca usalit y T E A Es. A t otal 
of 5 4 ( 8 1. 8 %) partici pa nts re p orte d treat me nt -relate d T E A Es d uri n g t he st u d y. 1 6 ( 2 4. 2 %) of 
partic i pa nts re p orte d Gra de 3 treat me nt-relate d T E A Es. N o Gra de 4 or 5 treat me nt-relate d 
T E A E were re p orte d. A t otal of 4 ( 7. 3 %) partici pa nts of t he 5 5 D L T e val ua ble partici pa nts 
e x perie nce d D L Ts. A t otal of 1 3 ( 1 9. 7 %) partici pa nts re p orte d all -ca usalit y S A Es; of t hese 3 
( 4. 5 %) partici pa nts re p orte d S A Es w hic h were c o nsi dere d t o be relate d t o t he st u d y dr u g by 
t he i n vesti gat or. A t otal of 3 ( 4. 5 %) partici pa nts disc o nti n ue d t he st u d y d ue t o A Es. O ne 
( 1. 5 %) partici pa nt disc o nti n ue d st u d y d ue t o A Es (le u k o pe nia a n d ne utr o pe nia) i n 3 0 0 m g 
BI D + Letr oz ole c o h ort t hat were relate d t o treat me nt dr u g, as per t he i n vesti gat or.
As of t he data c ut - off date of 1 2 Se pte m ber 2 0 2 2 f or C 4 3 9 1 0 0 2, a t otal of 1 2 partici pa nts 
ha ve recei ve d P F- 0 7 2 2 0 0 6 0 i n c o m bi nati o n wit h P F - 0 7 1 0 4 0 9 1 (selecti ve C D K 2 i n hi bit or) 
acr oss 4 d ose c o h orts. Of t he 1 2 treate d partici pa nts, 1 0 ( 8 3. 3 %) partici pa nts re p orte d a t otal 
of 8 8 T E A Es. M ost fre q ue ntl y  re p orte d (≥2 0 %) all -ca usalit y were na usea ( 5 8. 3 %), diarr h oea, 
ne utr o p hil c o u nt decrease d a n d w hite bl o o d cell c o u nt decrease d ( 5 0. 0 % eac h), a nae mia 
( 4 1. 7 %), ly m p h oc y te c o u nt decrease d ( 3 3. 3 %), fati g ue, platelet c o u nt decrease d a n d 
v o miti n g ( 2 5. 0 % eac h). N o Gra de 4 T E A Es were re p orte d. O ne Gra de 5 T E A E of disease 
pr o gressi o n was re p orte d d uri n g t he st u d y. A t otal of 1 0 ( 8 3. 3 %) of t he 1 2 partici pa nts 
re p orte d treat me nt-relate d T E A Es. M ost fre q ue ntl y re p orte d (≥2 0 %) treat me nt -relate d A Es 
were na usea ( 5 8. 3 %), diarr h oea, ne utr o p hil c o u nt decrease d a n d w hite bl o o d cell c o u nt 
decrease d ( 5 0. 0 % eac h), l y m p h oc y te c o u nt decrease d ( 3 3. 3 %), a nae mia, fati g ue, platelet 
c o u nt decrease d a n d v o miti n g ( 2 5. 0 % eac h). N o Gra de 4 or 5 treat me nt -relate d T E A Es were 
re p orte d d uri n g t he st u dy. As of t he data c ut -off date, t here was 1 D L T ( Gra de 3 fati g ue) 
re p orte d i n 1 partici pa nt w h o recei ve d P F-0 7 2 2 0 0 6 0 3 0 0 m g BI D + P F -0 7 1 0 4 0 9 1 1 5 0 m g 
BI D.
F urt her details o n t he cli nical safet y i nf or mati o n wit h P F -0 7 2 2 0 0 6 0 are pr o vi de d i n t he 
c urre nt I B.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 2. 4. 2. Effic ac y O ver vie w
P F -0 7 2 2 0 0 6 0 has de m o nstrate d earl y  si g ns of a nti-t u m or acti vit y i n c o m bi nati o n wit h E T i n 
H R +/ Her 2 - metastatic breast ca ncer patie nt p o p ulati o n. Efficac y  e val uati o n i n d ose 
e x pa nsi o n c o h orts at R D E i n c o m bi nati o n wit h f ul vestra nt a n d letr oz ole is o n g oi n g.
2. 2. 4. 3. S u m m ar y of P F -0 7 2 2 0 0 6 0 P h ar m ac o ki netics i n H u m a ns
I n t he o n g oi n g st u dy C 4 3 9 1 0 0 1 , as of 3 0 A u g ust 2 0 2 2, preli mi nar y P K data f or P F- 0 7 2 2 0 0 6 0 
as m o n ot hera p y a n d i n c o m bi nati o n wit h E T was a vaila ble fr o m 6 0   partici pa nts wit h 
a d va nce d s oli d t u m ors. P F -0 7 2 2 0 0 6 0 was a d mi nistere d orall y  as a si n gle a ge nt at d oses 
ra n gi n g fr o m 1 0 0 t o 5 0 0 m g BI D, a n d i n c o m bi nati o n wit h eit her letr oz ole or f ul vestra nt at 
3 0 0 t o 4 0 0 m g BI D. A vaila ble plas ma c o nce ntrati o n- ti me data of P F-0 7 2 2 0 0 6 0 were 
a nal yz e d usi n g n o nc o m part me ntal met h o ds.
Preli mi nar y  P K res ults s h o we d t hat P F- 0 7 2 2 0 0 6 0 was ra pi dly a bs or be d f oll o wi n g oral 
a d mi nistrati o n, wit h me dia n T ma x val ues of 1 t o 4 h o urs. T he plas ma e x p os ure para meters of 
P F -0 7 2 2 0 0 6 0, i ncl u di n g C ma x, A U C, a n d Cmi n , ge nerall y i ncrease d wit h d ose fr o m 1 0 0 t o 
3 0 0   m g BI D f or b ot h C ycle 1 Da y 1 a n d C ycle 1 Da y 1 5. T he stea d y  state e x p os ure was 
i ncrease d i n a less t ha n d ose pr o p orti o nal ma n ner. N o s u bsta ntial i ncrease i n plas ma e x p os ure 
was o bser ve d at d oses hi g her t ha n 3 0 0 m g BI D. M o derate acc u m ulati o n of t he A U C was 
o bser ve d f oll o wi n g re peate d BI D d osi n g . P K of P F -0 7 2 2 0 0 6 0 as m o n ot hera p y  a n d i n 
c o m bi nati o n wit h letr oz ole or f ul vestra nt were ge nerall y c o m para ble. P F -0 7 2 2 0 0 6 0 e x hi bite d 
m o derate i nter -s u bject varia bilit y wit h ge o metric mea n C V of 1 1-7 7 % f or stea d y  state Cma x
a n d 4 0-7 0 % f or A U C ta u i n t he m o n ot hera py c o h orts, 2 4 - 4 2% f or stea d y C m a x a n d 1 5-2 8 % f or 
A U C ta u i n t he c o m bi nati o n wit h E T c o h orts.
F urt her details o n t he cli nical P K of P F-0 7 2 2 0 0 6 0 are pr o vi de d i n t he c urre nt I B.
2. 3. Be nefit/ Ris k Assess me nt
P F - 0 7 2 2 0 0 6 0 will n ot pr o vi de a n y cli nical be nefit t o healt h y partici pa nts i n t his st u d y. T his 
st u d y is desi g ne d pri maril y t o assess h u ma n P K, a bs or pti o n, meta b olis m, a n d eli mi nati o n of 
P F - 0 72 2 0 0 6 0 f oll o wi n g oral a n d IV a d mi nistrati o ns . Partici pa nts 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 assess me nts. Ta ki n g i nt o 
acc o u nt t he meas ures t o mi ni mize ris k t o partici pa nts i ncl u di n g si n gle d ose a d mi nistrati o n 
a n d cl ose m o nit ori n g at C R U , t he p ote ntial ris ks ass ociate d wit h P F- 0 7 2 2 0 0 6 0 are j ustifie d 
b y  t he a ntici pate d be nefits t hat ma y be aff or de d by f urt heri n g t he u n dersta n di n g of 
P F - 0 7 2 2 0 0 6 0.
St u d y  C 4 3 9 1 0 1 0 is t he first ti me t hat [1 4C] P F - 0 7 2 2 0 0 6 0 will be a d mi nistere d t o healt h y a d ult 
partici pa nts , a n d will be t he first ti me t hat I V i nf usi o ns of P F-0 7 2 2 0 0 6 0 are a d mi nistere d t o 
h u ma ns . Pri or t o t his st u d y , P F-0 7 2 2 0 0 6 0 has bee n a d mi nistere d as m o n ot hera p y or i n 
c o m bi nati o n wit h ot her a nti -ca ncer a ge nts t o patie nts wit h a d va nce d ca ncer at starti n g d os es 
ra n gi n g fr o m 1 0 0 m g t o 5 0 0 m g BI D c o nti n u o usl y. Base d o n t he a vaila ble data fr o m St u d y 
C 4 3 9 1 0 0 1, t he cli nical safet y  pr ofile fa v ors f urt her de vel o p me nt of P F-0 7 2 2 0 0 6 0. Base d o n 
t he res ults of t he n o ncli nical t o xicit y st u dies (Secti o n 2. 2. 3 ), t he p ote ntial ris k of 
P F -0 7 2 2 0 0 6 0 a d mi nistrati o n t o healt h y partici pa nts ca n be ma na ge d a de q uatel y , a n d be 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
miti gate d wit h pre ve nti ve meas ures i n place t hat i ncl u des r o uti ne m o nit ori n g of A Es a n d 
c ha n ges i n cli nical la b orat or y  test para meters f or cli nical ma na ge me nt.
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 Es of P F-0 7 2 2 0 0 6 0 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. 
Ref er 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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
Mit i g ati o n Str ate g y
St u d y I nter ve nti o n: P F -0 7 2 2 0 0 6 0
P ote ntial effects of P F -0 7 2 2 0 0 6 0 o n fertilit y, 
pre g na nc y, a n d lactati o n.
At t his ti me, it is n ot k n o w n w het her P F -0 7 2 2 0 0 6 0 
ca n ca use fetal har m w he n a d mi nistere d t o pre g na nt 
w o me n. A ni mal re pr o d ucti ve st u dies ha ve n ot bee n 
c o n d ucte d wit h P F -0 7 2 2 0 0 6 0. It is als o n ot k n o w n 
w het her P F -0 7 2 2 0 0 6 0 ca n affect male or fe male 
fertilit y, or w het her P F-0 7 2 2 0 0 6 0 is secrete d i n 
h u ma n mil k. P F -0 7 2 2 0 0 6 0 
i n rats a n d d o gs o n re peat a d mi nistrati o n a n d 
t heref ore, ma y p ote ntiall y i m pact
Eli gi bilit y criteria a n d t he c o ntrace pti ve lifest yle 
re q uire me nts ( d urati o n of ca uti o n of c o ntrace pti o n 
da ys f or  
partici pa nts ) f or t his pr ot oc ol ha ve 
bee n crafte d t o miti gate t hese i de ntifie d p ote ntial 
ris ks. Partici pa nts will be i nstr ucte d a n d m o nit ore d 
o n t he c o ntrace pti ve re q uire me nts i m ple me nte d t o 
mi ni mize p ote ntial ris ks.
P ote ntial ris ks ass ociate d wit h P F -0 7 2 2 0 0 6 0 i ncl u de 
t he f oll o wi n g: he mat ol o gical t o xicities (i ncl u di n g 
a ne mia a n d ne utr o pe nia) a n d gastr oi ntesti nal 
t o xicities (s uc h as na usea, v o miti n g a n d diarr hea).
T he ris ks are base d o n e mer gi n g cli nical data fr o m t he 
o n g oi n g cli nical st u d y C 4 3 9 1 0 0 1 f oll o wi n g 
c o nti n u o us a d mi nistrati o n of P F -0 7 2 2 0 0 6 0 t o 
a d va nce d ca ncer patie nts at d oses ra n gi n g fr o m 1 0 0 t o 
5 0 0 m g BI D.
T he prese nt st u d y will o nl y test si n gle 1 0 0 m g oral 
d ose of P F -0 7 2 2 0 0 6 0
A E s a n d cli nical la b orat or y res ults will be m o nit ore d 
o n a n o n g oi n g basis.
St u d y Pr oce d ures
E x p os ure t o ra diati o n
T his st u d y i n v ol ves usi n g ra di oacti ve mar kers (la bels) 
d uri n g oral a d mi nistrati o n i n C o h ort 1 a n d I V i nf usi o n 
i n C o h ort 2 . Ra diati o n ma y ca use si de effects 
i ncl u di n g fati g ue, hair l oss, na usea, v o miti n g, l o w 
bl o o d c o u nts, s ki n pr o ble ms a n d e ve n ca ncer. 
T h e a m o u nt of ra diati o n a d mi nistere d t o eac h 
partici pa nt is ver y l o w,  
 n Ci, eit her p. o. or i. v., 
a n d bel o w t he li mit s u g geste d i n t he F D A G ui da nce 
t hat c o ul d be e xe m pte d fr o m d osi metr y calc ulati o ns. 
Base d o n l o n g -sta n di n g e x perie nce, t he ra diati o n 
b ur de n will be bel o w  0. 1 mS v, ie, I C R P Cate g or y I, 
tri vial ris k of healt h da ma ge d ue t o t he e x p os ure t o 
i o nisi n g ra diati o n. 
 
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 3. 2. Be nefit Assess me nt
P F -0 7 2 2 0 0 6 0 will n ot pr o vi de a n y cli nical be nefit t o healt h y partici pa nts i n t his st u d y . T his 
st u d y is desi g ne d pri maril y t o f urt her t he u n dersta n di n g of h u ma n P K, a bs or pti o n, 
meta b olis m, a n d eli mi nati o n of P F -0 7 2 2 0 0 6 0 f oll o wi n g oral a n d I V a d mi nistrati o ns .
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
Base d o n a vaila ble cli nical data wit h P F - 0 72 2 0 0 6 0 (Secti o n 2. 2. 4 a n d c urre nt I B), a si n gle
1 0 0 m g oral d ose ( C o h ort 1), a n d a si n gle 1 0 0 m g  oral d ose f oll o we d by  
μ g I V d ose
( C o h ort 2) are a ntici pate d t o be safe a n d well t olerate d. Eac h partici pa nt will be e x p ose d t o
a p pr o xi matel y 
n Ci o ver t he e ntire st u d y d urati o n, w hic h i ncl u des d osi n g
[1 4C] P F - 0 7 2 2 0 0 6 0 i n C o h ort 1 a n d C o h ort 2. T his is classe d as a micr otracer d ose, wit h o ut
a n y a ntici pate d ris k t o st u d y partici pa nts.
Base d o n t he pr ofile of P F- 0 7 2 2 0 0 6 0 o bser ve d i n n o ncli nical a n d cli nical st u dies t o date, a n d
t he meas ures ta ke n as part of t he st u d y t o mi ni mize ris k t o st u d y partici pa nts, t he p ote ntial 
ris ks ass ociate d wit h P F- 0 7 22 0 0 6 0 are j ustifie d b y  t he a ntici pate d be nefits t hat ma y be 
aff or de d b y f urt heri n g t he u n dersta n di n g of P F -0 7 2 2 0 0 6 0.
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 c haracterize t he rate a n d e xte nt of 
e xcreti o n of t otal ra di oacti vit y f oll o wi n g 
a d mi nistrati o n of a si n gle oral d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 . 

Mass Bala nce: C u m ulati ve rec o ver y ( %) of ra di oacti vit y 
i n uri ne a n d feces (a dj uste d f or v o mit us, if a n y), 
e x presse d as a perce nt of t otal oral ra di oacti ve d ose 
a d mi nistere d (q ua ntificati o n b y A M S) .

T o c haracterize t he meta b olic pr ofile f or 
P F -0 7 2 2 0 0 6 0 a n d i de ntif y t he circ ulati n g 
a n d e xcrete d meta b olites of P F -0 7 2 2 0 0 6 0
f oll o wi n g a d mi nistrati o n of a si n gle oral 
d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 .

Meta b olic pr ofili n g/ meta b olite i de ntificati o n a n d 
deter mi nati o n of relati ve a b u n da nce of [1 4C] P F -
0 7 2 2 0 0 6 0 a n d its meta b olites i n plas ma, uri ne a n d feces, 
if p ossi ble ( C o h ort 1).
Sec o n d ar y: 
Sec o n d ar y:

T o deter mi ne t he a bs ol ute oral 
bi oa vaila bilit y ( F) of P F -0 7 2 2 0 0 6 0 fr o m a 
si n gle oral d ose of P F-0 7 2 2 0 0 6 0 u n der 
faste d c o n diti o ns f oll o we d b y a si n gle I V 
micr o d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 .

T he rati o of d ose -n or m alize d plas ma A U C i nf of oral 
P F -0 7 2 2 0 0 6 0 ( L C M S) a n d I V [1 4C] P F -0 7 2 2 0 0 6 0
( H P L C-A M S) [ C o h ort 2 o nl y ].

T o deter mi ne t he fracti o n of P F -0 7 2 2 0 0 6 0
d ose a bs or be d ( F a) fr o m a si n gle oral d ose 
of [ 1 4C] P F -0 7 2 2 0 0 6 0 u n der faste d 
c o n diti o ns.

F a calc ulate d fr o m t he rati o of t otal rec o vere d 
ra di oacti vit y [1 4C] i n uri ne f oll o wi n g si n gle d ose 
a d mi nistrati o n of [ 1 4C] P F -0 7 2 2 0 0 6 0 orall y i n C o h ort 1 
a n d via I V i nf usi o n i n C o h ort 2 ( q ua ntificati o n b y 
A M S).

T o deter mi ne t he safet y a n d t olera bilit y of 
P F -0 7 2 2 0 0 6 0 , a d mi nistere d as a si n gle oral 
d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 or a si n gle oral 
d ose of P F -0 7 2 2 0 0 6 0 f oll o we d b y 
a d mi nistrati o n of a si n gle I V d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 .

A E m o nit ori n g, p h ysical e xa mi nati o n, cli nical 
la b orat or y meas ure me nts, vital si g ns a n d 1 2 -lea d E C Gs.
Terti ar y/ E x pl or at or y:
Terti ar y/ E x pl or at or y:

T o c haracterize t he meta b olic pr ofile a n d 
i de ntif y t he circ ulati n g a n d e xcrete d 
meta b olites of P F -0 7 2 2 0 0 6 0 f oll o wi n g 
a d mi nistrati o n of a si n gle oral d ose of 
P F -0 7 2 2 0 0 6 0 f oll o we d b y a d mi nistrati o n 
of a si n gle I V d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0
(as nee de d).

C o nti n ge nt m eta b olic pr ofili n g/ meta b olite i de ntificati o n 
an d deter mi nati o n of relati ve a b u n da nce of 
[1 4C] P F -0 7 2 2 0 0 6 0 a n d t he meta b olites of 
[1 4C] P F -0 7 2 2 0 0 6 0 i n plas ma, uri ne a n d feces, if p ossi ble 
(C o h ort 2).

T o deter mi ne t he plas ma P K para meters of 
a si n gle oral d ose of P F -0 7 2 2 0 0 6 0
f oll o wi n g a d mi nistrati o n as a si n gle oral 
d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 or a si n gle oral 
d ose of P F -0 7 2 2 0 0 6 0 f oll o we d b y 
a d mi nistrati o n of a si n gle I V micr o d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 .

Plas ma P K para meters of P F -0 7 2 2 0 0 6 0 fr o m L C M S 
a nal yses ( C o h ort 1 a n d C o h ort 2): 

A U C last, Cma x , Tma x . 

If data per mits: A U C i nf, t½ , Vz/ F, C L/ F.

T o deter mi ne plas ma P K para meters of 
[1 4C] P F -0 7 2 2 0 0 6 0 f oll o wi n g a d mi nistrati o n 

Plas ma P K para meters of [ 1 4C] P F -0 7 2 2 0 0 6 0 fr o m 
H P L C -A M S a nal yses ( C o h ort 2): 

A U C last, Cma x , T ma x .
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
O bjecti ves
E n d p oi nts
of a si n gle I V m icr od ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 .

If data per mits: A U Ci nf, t½ , C L, Vss.

T o deter mi ne t he uri ne P K para m eters of 
P F -0 7 2 2 0 0 6 0 f oll o wi n g a d mi nistrati o n as a 
si n gle oral d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 (if 
meas ure d)

Uri ne P K para meters of P F -0 7 2 2 0 0 6 0 fr o m L C M S 
(C o h ort 1):

C L R , Ae(∞), a n d A e %.

T o deter mi ne plas ma P K para meters of 
t otal ra di oacti vit y f oll o wi n g a d mi nistrati o n 
of a si n gle oral d ose of [ 1 4C] P F -0 7 2 2 0 0 6 0 .

Plas ma P K para meters of t otal ra di oacti vit y [ 1 4C] fr o m 
A M S a nal yses ( C o h ort 1): 

A U C last, Cma x , Tma x of t otal ra di oacti vit y.

If data per mit: A U Ci nf, t½ .

T o deter mi ne plas ma P K para meters of 
t otal ra di oacti vit y f oll o wi n g a si n gle oral 
d ose of P F -0 7 2 2 0 0 6 0 f oll o we d b y 
a d mi nistrati o n of a si n gle I V d ose of 
[1 4C] P F -0 7 2 2 0 0 6 0 (as nee de d).

Plas ma P K para meters of t otal ra di oacti vit y [ 1 4C] f r o m 
A M S a nal yses ( C o h ort 2): 

A U C last, Cma x , Tma x of t otal ra di oacti vit y.

If data per mit: A U Ci nf, t½ .

T o e x pl ore t he i m pact of 
p har mac o ge n o mics o n a bs or pti o n, 
distri b uti o n, meta b olis m a n d e xcreti o n of 
[1 4C]- P F -0 7 2 2 0 0 6 0 a n d t he a bs ol ute 
bi oa vaila bilit y a n d fracti o n a bs or be d of 
P F -0 7 2 2 0 0 6 0.

Allelic varia nts of dr u g meta b olizi n g e nz y mes a n d 
tra ns p orters

T o e val uate t he se ns or y a n d taste attri b utes 
of t he P F -0 7 2 2 0 0 6 0 oral s us pe nsi o n i n 
healt h y partici pa nts u n der faste d 
c o n diti o ns.

T aste Assess me nt S ur ve y Sc ori n g Metrics: m o ut hfeel, 
bitter ness, s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h 
b ur n, t hr oat b ur n, a n d o verall li ki n g.
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  will be a P hase 1, o pe n- la bel, parallel- gr o u p, si n gle -d ose st u d y of P F - 0 7 2 2 0 0 6 0 t o 
c haracterize t he meta b olic pr ofile a n d r o utes of e xcreti o n f or oral [1 4C] P F - 0 7 2 2 0 0 6 0 a n d t o 
e val uate F of P F -0 7 2 2 0 0 6 0 a n d F a of [ 1 4C] P F -0 7 2 2 0 0 6 0 , i n refere nce t o I V mictr otracer 
[1 4C] P F - 0 7 2 2 0 0 6 0 i n faste d healt hy male partici pa nts. 
I n or der t o ac hie ve s ufficie nt bi oa nal ytical se nsiti vit y f or t he micr otracer d ose a n d 
differe ntiate t he plas ma c o nce ntrati o ns res ulti n g fr o m t he ra di ola bele d I V d ose a n d t h ose 
res ulti n g fr o m t he oral d ose, t he ultra-se nsiti ve A M S met h o d will be use d t o q ua ntif y plas ma 
c o nce nt rati o ns of ra di ola bele d pare nt dr u g as well as t otal ra di oacti vit y [1 4C] deri ve d fr o m 
t he micr otracer d ose base d o n meas ure me nt of 1 4C. T he oreticall y , Fa w o ul d be e x pecte d t o be 
greater t ha n F. I n t he e ve nt t hat F is esti mate d t o be greater t ha n Fa ( beca use of t he p ossi bilit y 
t hat F is li kel y t o be m ore precisel y esti mate d d ue t o a nal ytical tec h ni q ues), t he greater of t he 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2 val ues will be use d t o re prese nt t he fracti o n of P F - 0 7 2 2 0 0 6 0 a bs or be d. P F- 0 7 2 2 0 0 6 0 will 
be c o nsi dere d hi g hl y per mea ble if eit her F or F a is greater t ha n 0. 9 (as per B C S g ui da nce).2
A p pr o xi matel y  6 healt h y a d ult male partici pa nts will be e nr olle d i n eac h of t he 2 c o h orts.
P artici pa nts i n C o h orts 1 a n d 2 will recei ve treat me nt re gi me n A a n d B, res pecti vel y. If t here 
are partici pa nts w h o wit h dra w or disc o nti n ue treat me nt a n d are c o nsi dere d t o be n o n -
e val ua ble wit h res pect t o t he pri mar y a n d sec o n dar y P K o bjecti ve (s), a d diti o nal partici pa nts 
ca n be e nr olle d at t he discreti o n of t he i n vesti gat or u p o n c o ns ultati o n wit h t he s p o ns or. T he 
S o A f or C o h orts 1 a n d 2 (Ta ble 1 a n d Ta ble 2 , res pecti vely) descri bes
pr oce d ures/assess me nts t o be c o n d ucte d fr o m c hec k-i n t o t he C R U o n Da y - 1 u p t o t he 
disc har ge da y occ urri n g bet wee n Da y s 5 t o 1 4 of eac h c o h ort.
Scree ni n g will occ ur wit hi n 2 8 da y s of t he first d ose of i n vesti gati o nal pr o d uct. All
partici pa nts will pr o vi de i nf or me d c o nse nt a n d u n der g o scree ni n g e val uati o ns t o deter mi ne
t heir eli gi bilit y. Eli gi ble partici pa nts will be a d mitte d t o t he C R U o n Da y - 1. Pri or t o d osi n g 
i n b ot h C o h orts , pre-d ose uri ne sa m ples m ust be c ollecte d wit hi n 2 4 hrs pri or t o d osi n g a n d 
pre -d ose fecal sa m ples m ust be c ollecte d wit hi n 4 8 hrs pri or t o d osi n g ( ma y  be c ollecte d at 
h o me). T he last c ollecte d fecal sa m pl e will be use d as pre-d ose sa m ple a n d all pre vi o us pre -
d ose sa m ples will be destr o y e d. 
Re gar dless of w het her or n ot t he disc har ge criteria f or eac h c o h ort ha ve bee n met, n o 
partici pa nt will be c o nfi ne d b e y o n d Da y  1 4 f or b ot h C o h orts. T he ma xi m u m t otal i n -h o use 
partici pati o n ti me f or eac h partici pa nt i n t his st u d y is a p pr o xi matel y  1 5 d a y s a n d 1 4 ni g hts. 
Partici pa nts will ha ve a f oll o w-u p p h o ne call at 2 8 - 3 5 d a y s after t he last d ose of st u d y 
i nter ve nti o n.
C o h ort 1 : A s i n gle oral d ose of 10 0 m g 1 4C -la bele d P F - 0 7 2 2 0 0 6 0 c o ntai ni n g a p pr o xi matel y 
 n Ci 1 4C (ie, “li g htl y ra di ola bele d” or micr otracer [1 4C ]P F - 0 7 2 2 0 0 6 0) will be
a d mi nistere d f oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs . D osi n g will i n v ol ve 
a d mi nistrati o n of m ulti ple ri nses of t he d osi n g c o ntai n er, a n d a n assess me nt of t he resi d ual 
ra di oacti vit y o n t he d osi n g c o ntai ner will be re q uire d t o be assesse d a n d d oc u me nte d i n t he 
st u d y C R F (see als o Secti o n 6. 1. 1 ). Bl o o d, uri ne, feces, a n d v o mit us (if a ny) sa m ples will be
c ollecte d as detaile d i n t he S o A u p u ntil t he disc har ge da y  occ ur s bet wee n Da y s 5 t o 1 4. 
Disc har ge ma y  occ ur f or partici pa nts w h o meet at least o ne of t he 2 ra di oacti vit y rec o ver y 
criteria or reac he d t he ma xi m um d urati o n of i n -h o use sta y . T he disc har ge criteria are: ( 1) at 
least 9 0 % of t he a d mi nistere d ra di oacti ve d ose has bee n rec o vere d i n uri ne +feces + v o mit us 
(if a ny) , ( 2) < 1 % of t he a d mi nistere d ra di oacti ve d ose has bee n rec o vere d i n uri ne +feces 
d uri n g 2 4 -h o ur i nter vals o ver 2 c o nsec uti ve da ys, or ( 3) t he partici pa nt has reac he d Da y  1 4. 
Eac h b o wel m o ve me nt m ust be c ollecte d , a n d ti me a n d date m ust be rec or de d. If a n 
i n di vi d ual partici pa nt has n ot e x perie nce d a b o wel m o ve me nt wit hi n 3 6 hrs of t heir pre vi o us 
b o wel m o ve me nt, fl ui d i nta ke s h o ul d be i ncrease d a n d a d mi nistrati o n of a mil d la xati ve (e g, 
pr u ne j uice or a mil d st o ol s ofte ner) s h o ul d be i m ple me nte d, wit h t he g oal t o facilitate at least 
o nce dail y b o wel m o ve me nt. T he use of t he la xati ve s h o ul d be rec or de d i n t he C R F.
V o mit us, if a n y , will be c ollecte d i n f ull d uri n g t he 
h o urs after oral d osi n g i n C o h ort 1 a n d 
will be re q uire d t o be pr os pecti vel y  teste d f or rec o vere d ra di oacti vity. F or e mesis t hat occ urs 
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
after 
h o urs u p t o  
h o urs p ost d ose, sa m ples wil l be c ollecte d i n f ull a n d st ore d f or 
p ote ntial refle x testi n g f or rec o vere d ra di oacti vit y . T he ti me a n d date of a n y v o miti n g e ve nt 
wit hi n t he first 
 h o urs p ost- d ose m ust be rec or de d. Partici pa nts w h o e x perie nce e mesis 
f oll o wi n g oral d osi n g will n ot necessaril y be e xcl u de d fr o m a nal ysis (see Secti o n 9. 3 f or 
a d diti o nal details o n e val ua ble partici pa nts).
C o h ort 2 : A s i n gle oral d ose of 10 0 m g u nla bele d P F -0 7 2 2 0 0 6 0 will be a d mi nistere d 
f oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs f oll o we d b y a n I V micr otracer micr o d ose of 
µ g [1 4C] P F - 0 7 2 2 0 0 6 0 c o ntai ni n g a p pr o xi matel y   
n Ci 1 4C at t he a p pr o xi mate ti me of 
a ntici pate d pea k plas ma c o nce ntrati o n ( T ma x ). T he 1 4C I V d ose will be a d mi nistere d as a n 
i nf usi o n o ver a p pr o xi matel y 3 0 mi n utes starti n g at a p pr o xi matel y 2 h o ur ( a ntici pate d T ma x ) 
after t he a d mi nistrati o n of t he u nla bele d oral d ose. Bl o o d, uri ne, feces, a n d v o mit us (if a n y) 
sa m ples will be c ollecte d as detaile d i n t he S o A u p u ntil t he disc har ge da y occ urs bet wee n 
D a y s 5 t o 1 4. T he d urati o n of c o nfi ne me nt f or C o h ort 2 will e q ual t he l o n gest i n di vi d ual 
partici pa nt d urati o n of c o nfi ne me nt i n C o h ort 1 s o t hat t he d urati o n of uri ne sa m p le 
c ollecti o ns o ver t he peri o ds is c o nsiste nt t o ai d i n acc urate esti mati o n of t he Fa. 
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 he st u d y  is t o assess t he meta b olis m a n d e xcreti o n of [1 4C] P F - 0 7 2 2 0 0 6 0
f oll o wi n g oral a d mi nistrati o n u n der faste d state c o n diti o ns i n healt h y male partici pa nts. T his 
i nf or mati o n will e na ble assess me nt of pri mar y a n d sec o n dar y cleara nce mec ha nis ms of 
P F - 0 7 2 2 0 0 6 0 as well as i de ntif y dis pr o p orti o nate meta b olites t hat s h o ul d be q ualifie d t o 
a d here t o t he I CH ( M 3) R 2 g ui da nce. I n a d diti o n, t his st u d y  will esti mate t he t he fracti o n 
a bs or be d a n d bi oa vaila bilit y of oral P F- 0 7 2 2 0 0 6 0 a d mi nistere d u n der faste d c o n diti o ns i n 
refere nce t o a n I V d ose of [1 4C] P F - 0 7 2 2 0 0 6 0 a n d- will als o assess plas ma a n d uri ne P K 
para meters of P F -0 7 2 2 0 0 6 0 f oll o wi n g b ot h oral a n d I V a d mi nistrati o n of [1 4C] P F - 0 7 2 2 0 0 6 0. 
T his c haracterizati o n of a bs or pti o n a n d oral bi oa vaila bilit y  will e na ble t he n o mi nati o n of 
a p pr o priate B C S desi g nati o n f or P F- 0 7 2 2 0 0 6 0.
T he st u d y is bei n g desi g ne d as a parallel -c o h ort st u d y i ncl u di n g 2 i n de pe n de nt c o h orts
wit h o ut cr oss o ver . C o h ort 2 will be e nr olle d a p pr o xi matel y 1 5 da y s after C o h ort 1 
e nr oll me nt. C o h orts 1 a n d 2 are e nr olle d se q ue ntiall y usi n g a si n gle d ose lifeti me 
e x peri me ntati o n ( o ne si n gle P F -0 7 2 2 0 0 6 0 d ose, n o cr oss o ver ) 
O nl y  males will be i ncl u de d i n t his st u d y gi ve n t he desire t o e nr oll a h o m o ge ne o us 
p o p ulati o n d ue t o t he s mall sa m ple size of t his st u d y . D osi n g of P F -0 7 2 2 0 0 6 0 is pla n ne d t o 
occ ur i n t he f aste d state, w hic h is c o nsiste nt wit h t he a d mi nistrati o n c o n diti o n i n t he d ose 
fi n di n g a n d d ose o pti mizati o n parts o f P hase 1 st u d y C 4 3 9 1 0 0 1 i n patie nts wit h ca ncer .
D ue t o lac k of data o n t he eli mi nati o n half li ves of P F - 0 7 2 2 0 0 6 0 meta b olites , t he mi ni m u m 
d urati o n of c o nfi ne me nt of
da y s was set as t he ti mefra me w he n circ ulati n g P F- 0 7 2 2 0 0 6 0 is 
e x pecte d t o reac h B L Q le vels as deter mi ne d base d o n t he plas ma half -life esti mate fr o m
p o p ulati o n P K m o deli n g. A n a d diti o nal  da y s of per mitte d e xte n de d sta y is t o all o w f or 
e xcreti o n of a n y u n k n o w n meta b olites wit h l o n ger half -li ves.
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T he d urati o n of c o nfi ne me nt a n d c ollecti o n of bl o o d, uri ne, a n d fecal sa m ples f or t he 
partici pa nt s i n C o h ort 2 will be matc he d wit h as t he l o n gest o ne fr o m C o h ort 1 i n or der t o 
best esti mate t he F a of P F - 0 7 2 2 0 0 6 0. 
I n t his st u dy, a “ micr otracer” a p pr oac h will be use d w her e t he [ 1 4C] d ose is m uc h l o wer t ha n 
tra diti o nal A D M E st u dies. Wit h t his a p pr oac h, [1 4C] will be q ua ntifie d usi n g a n A M S 
detecti o n tec h ni q ue. T his tec h n ol o g y  all o ws A D M E st u dies t o be c o n d ucte d wit h o ut W B A 
data, as c o nce ntrati o ns of [ 1 4C] a n d res ulti n g e x p o s ures are s o mi n ute t hat d osi metr y 
calc ulati o ns are n ot nee de d .1
C o h ort 1 of t he st u d y is desi g ne d t o e val uate t he meta b olic fate a n d mass bala nce of 
P F - 0 7 2 2 0 0 6 0 f oll o wi n g t he i nte n de d cli nical r o ute of a d mi nistrati o n ( oral) of 
[1 4C] P F - 0 7 2 2 0 0 6 0. In or der t o assess t he meta b olic fate of [ 1 4C] P F -0 7 2 2 0 0 6 0, meta b olites of 
[1 4C] P F -0 7 2 2 0 0 6 0 circ ulati n g i n plas ma a n d eli mi nate d i n uri ne a n d feces f oll o wi n g oral 
a d mi nistrati o n will be deter mi ne d usi n g A M S. A d diti o nall y , mass bala nce will be deter mi ne d 
b y  rec o ver y of t otal ra di oacti vit y e xcrete d i n uri ne a n d feces. Lastly, t he plas ma P K of 
P F - 0 7 2 2 0 0 6 0 ( via L C M S) will be c o m pare d t o plas ma P K of t otal ra di oacti vit y ( via A M S) 
f or deter mi nati o n of relati ve a b u n da nce as a n a d diti o nal wa y t o q ua ntif y circ ulati n g 
meta b olites.
C o h ort 2 of t he st u d y is desi g ne d t o e val uate t he F a n d esti mate F a of t he oral P F - 0 7 2 2 0 0 6 0
d ose. A micr otracer micr o d ose (
n Ci, 
µ g) of [1 4C] P F - 0 7 2 2 0 0 6 0 will be a d mi nistere d 
via a 3 0 mi n utes I V i nf usi o n at t he a p pr o xi mate T ma x f oll o wi n g a n oral u nla bele d
1 0 0 m g - d ose of P F -0 7 2 2 0 0 6 0 a n d la bele d [1 4C] P F - 0 7 2 2 0 0 6 0 i n plas ma will be assesse d via 
A M S f oll o wi n g c hr o mat o gra p hic se parati o n ( H P L C -A M S). F will be calc ulate d as t he rati o 
of d ose -n or malize d plas ma A U C i nf f oll o wi n g orall y a d mi nistere d P F-0 7 2 2 0 0 6 0 (ie, u nla bele d
P F - 0 7 2 2 0 0 6 0 assesse d b y LC M S) t o d ose -n or malize d- plas ma A U C i nf f oll o wi n g 
i ntra ve n o usl y a d mi nistere d [1 4C] P F -0 7 2 2 0 0 6 0 (ie [1 4C] P F - 0 7 2 2 0 0 6 0 assesse d b y H P LC-
A M S). 
I n C o h ort 2 , uri ne sa m ples will als o be c ollecte d at pre-s pecifie d i nter vals as descri be d i n t he 
S o A a n d t otal ra di oacti vit y e xcrete d i n uri ne f oll o wi n g i ntra ve n o usl y a d mi nistere d 
[1 4C] P F - 0 7 2 2 0 0 6 0, will be meas ure d via A M S. T he rati o of d ose-n or malize d t otal 
ra di oacti vit y rec o vere d i n uri ne f oll o wi n g oral a d mi nistrati o n of [1 4C] P F -0 7 2 2 0 0 6 0 i n C o h ort
1 t o t hat rec o vere d i n uri ne f oll o wi n g I V a d mi nistrati o n of [1 4C] P F - 0 7 2 2 0 0 6 0 i n C o h ort 2 
will esti mate t he F a f oll o wi n g oral a d mi nistrati o n of [1 4C] P F - 0 7 2 2 0 0 6 0. N ote, I V a n d oral 
ra di oacti vities will be c ollecte d fr o m partici pa nts i n differe nt c o h orts. Als o, t his calc ulati o n 
of F a ass u mes t hat meta b olites ge nerate d d uri n g first pass are n ot re nall y el i mi nate d a n d t hat 
pare nt dr u g e xcreti o n i n uri ne is mi ni mal f or dr u gs t hat u n der g o first pass meta b olis m. 
T heref ore, t he c o m p ute d F a s h o ul d be c o nsi dere d a n a p pr o xi mati o n. T here is n o safet y 
c o ncer n at ti me of disc har ge of C o h ort 2 gi ve n t hat o nl y  a micr otracer is d ose d i n t his st u d y.
Feces i n C o h ort 2 will be c ollecte d a n d will be assa y e d o nl y after mass bala nce of 
[1 4C] P F - 0 7 2 2 0 0 6 0 fr o m C o h ort 1 a n d uri nar y  ra di oacti vit y data fr o m C o h ort 2 is a vaila ble 
a n d o nl y if t he st u d y tea m deter mi nes t hat a nalys is of t otal ra di oacti vit y fr o m feces of 
C o h ort 2 w o ul d f urt her i nf or m dis p ositi o n of P F -0 7 2 2 0 0 6 0 i n h u ma ns.
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 9
T o ai d i n t he f ut ure de vel o p me nt of a p ote ntial pe diatric d osa ge f or m of P F- 0 7 2 2 0 0 6 0 , t he 
c urre nt st u d y will assess t he taste attri b utes of t he li q ui d f or m ulati o n i m me diatel y after 
( wit hi n 1 mi ns) a n d o ver 2 0 mi ns p ost oral d ose a d mi nistrati o n i n b ot h c o h orts. 
Ba n ke d bi os peci me ns i n b ot h c o h orts will be c ollecte d a n d st ore d f or f ut ure e x pl orat or y  
a nal ys es. P har mac o ge n o mic sa m p les fr o m b ot h c o h orts will be c ollecte d a n d a nal yz e d f or t he 
p ur p ose of assessi n g t he i m pact of allelic varia nts of ge nes e nc o di n g meta b olic e nz y mes s uc h 
as C Y P 3 A a n d U G T 2 B 7 (t he maj or meta b olizi n g e nz y mes i n v ol ve d i n t he meta b olis m of 
P F - 0 7 2 2 0 0 6 0 [Secti o n 2. 2. 2 ]).
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 2 2 0 06 0 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 (see A p pe n di x 4
a n d Secti o n 5. 3 ).
4. 3. J ustific ati o n f or D ose
I n t he P hase 1 st u dy C 4 3 9 1 0 0 1, P F -0 7 2 2 0 0 6 0 e x hi bite d a 
i n stea dy state plas ma e x p os ures a n d 
 
. 1 0 0 a n d 3 0 0 m g are t he selecte d rec o m me n de d 
d ose s f or e x pa nsi o n c o h orts a n d are c urre ntl y bei n g e val uate d i n a ra n d o mize d fas hi o n f or 
d ose o pti mizati o n wit h t he i nte nti o n of o ne bei n g selecte d as t he d ose f or f ut ure P hase 3 
trials. B ot h d ose le vels ha ve bee n f o u n d t o be safe a n d well t olerate d i n t he P hase 1 st u d y 
C 4 3 9 1 0 0 1. F or t h is st u d y, a si n gle d ose le vel will pr o vi de t he re q uire d data t o a de q uatel y 
c haracterize t he A D M E pr ofile of P F - 0 7 2 2 0 0 6 0 a n d 1 0 0 m g was selecte d base d o n its greater 
e x pos ure relati ve t o d ose size a n d li kel y hi g her oral bi oa vaila bilit y  i n c o m paris o n t o 
m g.
T he a ntici pate d plas ma e x p os ures of P F- 0 7 2 2 0 0 6 0 f oll o wi n g a d mi nistrati o n of a si n gle 
1 0 0 m g d ose t o male healt h y  v ol u nteers i n t his st u d y pr o vi de s ufficie nt safet y e x p os ure 
mar gi ns (
x) o ver t he e x p os ures o bser ve d at N O A E L d ose le vels i n t he rat n o ncli nical 
safety st u d y f or si n gle-d ose lifeti me e x peri me ntati o n i n healt h y  partici pa nts (Secti o n 2. 2. 3 ).
T he ra di oacti ve d ose a d mi nistere d i n b ot h c o h orts w o ul d be a p pr o xi matel y 
 n Ci of 1 4C. 
T his d ose of ra di oacti vit y  will all o w q ua ntificati o n of t he [1 4C] P F ‑ 0 7 2 2 0 0 6 0 b y hi g hly 
se nsiti ve A M S a nal ytical met h o d ol o g y (see Secti o n 4. 2 f or details).
A micr otracer micr o d ose of 
 µ g [1 4C] P F ‑ 0 7 2 2 0 0 6 0 is pla n ne d i n t his st u d y f or I V 
a d mi nistrati o n i n C o h ort 2. T he I V d ose of  
 µ g is 
% ( or a p pr o xi matel y
) of t he 
oral u nla bele d d ose of 1 0 0 m g a n d t heref ore e x pe cte d t o ha ve ne gli gi ble effect o n t he plas ma 
P K of u nla bele d P F ‑ 0 72 2 0 0 6 0 . As per t he I C H M 3 ( R 2), h u ma n a d mi nistrati o n of a n I V 
micr o d ose of u p t o 
 µ g ca n be s u p p orte d wit h n o ncli nical t o xic ol o g y st u dies w here t he 
dr u g is a d mi nistere d orall y  a n d wit h o ut t he nee d f or a d diti o nal n o ncli nical t o xic ol o g y st u dies 
via I V r o ute of a d mi nistrati o n.
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 partici pat i 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 partici pa nts 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 ys ical 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 t heir 
fe male part ners (Secti o n 1 0. 4. 2 ).
Ot her I ncl usi o n Criteri a : 
2.
B MI of 1 7. 5 -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.
E vi de nce of a pers o nall y  si g ne d a n d date d I C D i n dicati n g t hat t he partici pa nt has 
bee n i nf or me d of all perti ne nt as pects of t he st u d y.
4.
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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 u l m o nar y, gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, asy m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V , 
H b s A g, or H C V A b. He patitis B vacci nati o n is all o we d.
2.
Partici pa nt s wit h a hist or y of irre g ular b o wel m o ve me nts (e g, re g ular e pis o des of 
diarr hea or c o nsti pati o n, I B S or lact ose i nt olera nce).
3.
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 nor malit y  or ot her c o n diti o ns t hat ma y 
i ncrease t he ris k of st u d y partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he 
partici pa nt i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
4.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he si n gle oral d ose of 
st u d y i nter ve nti o n. (Refer t o Secti o n 6. 9 Pri or a n d C o nc o mita nt T hera p y f or 
a d diti o nal details).

C o nc o mita nt use of a n y me dicati o ns or s u bsta nces t hat are str o n g i n d ucers or 
i n hi bit ors of C Y P 3 A 4 or U G T 2 B 7 are pr o hi bite d wit hi n 5 half-li ves pl us 1 4 da ys 
( u p t o 2 8 da ys) pri or t o si n gle oral d ose of P F -0 7 2 2 0 0 6 0.

Use of pr ot o n -p u m p i n hi bit ors is pr o hi bite d fr o m 2 8 da y s pri or t o t he first d osi n g 
of st u d y  i nter ve nti o n, a n d t hr o u g h t he st u dy . Ot her aci d re d uci n g a ge nts i ncl u di n g 
H 2 -rece pt or a nta g o nists or l ocal a ntaci ds s h o ul d n ot be use d f or at least 7 da ys or 
5 half -li ves, w hic he ver is l o n ger, bef ore t he first d osi n g of st u d y  i nter ve nti o n a n d 
are pr o hi bite d wit hi n 5 da ys after t he d osi n g. 
5.
Partici pa nt s u n willi n g or u na ble t o use a re q uire d c o nc o mita nt me dicati o n(s). Refer t o 
Secti o n 6. 9 Pri or a n d C o nc o mita nt T hera p y.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
6.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves ( w hic he ver is 
l o n ger) 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. Pre vi o us 
e x p os ure t o P F -0 7 2 2 0 0 6 0 or partici pati o n i n st u dies re q uiri n g P F -0 7 2 2 0 0 6 0 
a d mi nistrati o n.
7.
Partici pa nt s e nr olle d i n a pre vi o us ra di o n ucle oti de st u d y  or w h o ha ve recei ve d 
ra di ot herap y  wit hi n 1 2 m o nt hs pri or t o scree ni n g or s uc h t hat t otal ra di oacti vit y 
w o ul d e xcee d acce pta ble d osi metr y.
Di a g n ostic Assess me nts:
8.
A p ositi ve uri ne dr u g test. A si n gle re peat f or p ositi ve dr u g scree n ma y  be all o we d.
9.
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 B P is ≥1 4 0 m m H g (s ys t olic) or 1 5 0 m m H g 
( base d o n a ge) or ≥9 0 m m H g ( diast olic), t he B P s h o ul d be re pe ate d 2 m ore ti mes a n d 
t he a vera ge of t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s 
eli gi bilit y.
1 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 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 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 is 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. T otal 1 4C ra di oacti vit y  meas ure d i n plas ma e xcee di n g 1 1 m B q/ m L.
1 2. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
scree ni n g, as assesse d by t he st u d ys pecific la b orat or y a n d c o nfir me d b y a si n gle 
re peat test, if dee me d necessar y:

A L T, A S T, b ilir u bi n ≥1. 0 5 × U L N; partici pa nts wit h a hist or y  of Gil bert’s 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤ U L N;

e G F R < 6 0 m L/ mi n/ 1. 7 3 m 2 base d o n t he 2 0 2 1 C K D -E PI (c o m bi ne d ser u m 
creati ni ne pl us ser u m c y stati n C) e q uati o n;

Bl o o d calci u m or p otassi u m < 0. 9 × L L N or > 1. 1 × U L N ;
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

A bs ol ute ne utr o p hil c o u nt < 0. 8 × L L N .
Ot her E xcl usi o n Criteri a :
1 3. 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) 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 4. Use of t o bacc o or nic oti ne c o ntai ni n g pr o d ucts wit hi n 3 m o nt hs of scree ni n g or a 
p ositi ve uri ne c oti ni ne test (ie, acti ve s m o kers a n d t h ose w h o c urre ntl y  use 
nic oti ne -c o ntai ni n g pr o d ucts are e xcl u de d fr o m partici pati o n i n t his st u d y ). 
1 5. Bl o o d d o nati o n (e xcl u di n g plas ma d o nati o ns) of a p pr o xi matel y  1 pi nt ( 5 0 0 m L ) or 
m ore wit hi n 6 0 da y s pri or t o d osi n g.
1 6. Hist or y  of se nsiti vit y t o he pari n or he pari n -i n d uce d t hr o m b oc yt o pe nia.
1 7. U n willi n g or u na ble t o c o m pl y  wit h t he criteria i n t he Li fest yle C o nsi derati o ns
secti o n of t his pr ot oc ol.
1 8. Partici pa nt s w h ose occ upati o n re q uires e x p os ure t o ra diati o n or m o nit ori n g of 
ra diati o n e x p os ure. 
1 9. 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 gat e e m pl o yees 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. 3 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. T he i n vesti gat or or desi g nee will a d vise t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  i nter ve nti o n, if 
a p plica ble.
At ti me p oi nts i n dicate d i n S o A , t he i n vesti gat or or desi g nee will i nf or m t he partici pa nt of 
t he nee d t o use hi g 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 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 4 h o urs pri or 
t o a n y safet y la b orat or y e val uati o ns a n d 1 0 h o urs pri or t o t he c ollecti o n of t he pre d ose 
P K sa m ple o n Da y  1. N o f o o d will be all o we d f or at least 4 h o urs p ost d ose o n Da y 1.

O n Da y  1, water will be 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. 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 o n Da y  1.

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 o n Da y  1.

A n e ve ni n g s nac k ma y  be per mitte d.

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi n e, 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 he ir t otal dail y n utriti o nal c o m p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat, a n d 1 5 % pr otei n. T he dail y cal oric i nta ke 
per partici pa nt s h o ul d n ot e xcee d a p pr o xi matel y 3 2 0 0 kcal.

Partici pa nt s will be as ke d t o a bstai n fr o m c o ns u mi n g i n di gesti ble materials (e g, c or n, 
n uts, etc) f or 2 da y s pri or t o d osi n g a n d f or t he d urati o n of t he st u d y i n or der t o 
facilitate ease of fecal h o m o ge nizati o n.

If a n i n di vi d ual p artici pa nt has n ot e x perie nce d a b o wel m o ve me nt i n a n y 3 6 h o ur 
peri o d p ost -d ose , fl ui d i nta ke s h o ul d be i ncrease d a n d a d mi nistrati o n of a mil d 
la xati ve (e g, pr u ne j uice or a mil d st o ol s ofte ner) s h o ul d be i m ple me nte d.

I n C o h ort 1, partici pa nt s will be c o nfi ne d fr o m t he e ve ni n g pri or t o t he first d ose u ntil 
at least t he m or ni n g of Da y
h o urs p ost d ose). If necessar y, uri ne a n d/ or fecal 
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
c ollecti o ns will c o nti n ue be yo n d Da y
u ntil Da y  1 4 or u ntil o ne of t he f oll o wi n g 
c o n diti o ns are met:

T he a m o u nt of c u m ulati ve ra di oacti vit y  rec o vere d i n e xcreta is at least 9 0 % of 
a d mi nistere d ra di oacti vit y, or

Less t ha n 1 % of t he a d mi nistere d ra di oacti vit y  has bee n rec o vere d i n e xcreta 
fr o m 2 c o nsec uti ve da ys (ie, t otal f or uri ne + feces s h o ul d < 1 % o n 
2 c o nsec uti ve da ys).
T he d urati o n of c o nfi ne me nt f or C o h ort 2 partici pa nts will e q ual t he l o n gest 
i n di vi d ual partici pa nts d urati o n of c o nfi ne me nt i n C o h ort 1.
5. 3. 3. C affei ne, Alc o h ol, a n d T o b acc o

Partici pa nts will a bstai n fr o m caffei ne -c o ntai ni n g pr o d ucts f or 2 4 h o urs pri or t o 
a d missi o n u ntil disc har ge .

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. 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.

Pa rtici pa nts will a bstai n fr o m t he use of t o bacc o- or nic oti ne -c o ntai ni n g pr o d ucts f or 
a peri o d of 3 m o nt hs bef ore scree ni 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. Act i 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 9 6 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;
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e nr olle d i n t he st u d y. Scree n fail ure data are c ollecte d a n d re mai n as 
s o urce a n d are n ot re p orte d o n t he C R F.
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y be 
rescree ne d.
 
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal, me dical de vices, a n d ot her 
i nter ve nti o ns (e g, s ur gical a n d be ha vi oral) i nte n de d t o be a d mi nistere d t o t he st u d y 
partici pa nts d uri n g t he st u d y  c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o P F -0 7 2 2 0 0 6 0 (eit her u nla bele d 
or [ 1 4C] P F - 0 7 2 2 0 0 6 0).
6. 1. St u d y I nter ve nti o n(s) A d mi nis tere d
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
[1 4C] P F -0 7 2 2 0 0 6 0
P F -0 7 2 2 0 0 6 0
[1 4C] P F -0 7 2 2 0 0 6 0
T y pe
Dr u g
Dr u g
Dr u g
Use
E x peri me ntal
E x peri me ntal
E x peri me ntal
I M P or A x M P
I M P
I M P
I M P
D ose F or m ul ati o n
Oral s us pe nsi o n  
Oral s us pe nsi o n
I V s ol uti o n
U nit D ose Stre n gt h(s)
1 0 0 m g
1 0 0 m g
µ g
D os a ge Le vel(s)
1 0 0 m g, si n gle d ose
1 0 0 m g, si n gle d ose
µ g, si n gle d ose
R o ute of 
A d mi nistr ati o n
Oral
Oral
I V i nf usi o n
S o urci n g
Pr o vi de d ce ntrall y b y 
t he s p o ns or. Refer t o 
E D R
Pr o vi de d ce ntrall y b y t he 
s p o ns or. Refer t o E D R
Pr o vi de d ce ntrall y b y t he s p o ns or.
Refer t o T A.
P ac k a gi n g a n d 
L a beli n g
[1 4C] P F - 0 7 2 2 0 0 6 0 
c o m p o ne nts will be 
s u p plie d b y Pfizer as b ul k 
A P I a n d b ul k e xci pie nts f or 
t he e xte m p ora ne o us 
pre parati o n  of t he [ 1 4C]
la bele d oral li q ui d 
f or m ulati o n.
U nla bele d P F - 0 7 2 2 0 0 6 0 
a n d e xci pie nts will be 
s u p plie d b y Pfizer as b ul k 
p o w ders f or 
e xte m p ora ne o us 
pre parati o n.
[1 4C] P F -0 7 2 2 0 0 6 0 c o m p o ne nts 
will be s u p plie d b y Pfizer, as b ul k 
A P I a n d, w here necessar y, b ul k 
e xci pie nts f or t he ma n u fact ure of 
t he [1 4C]  la bele d I V li q ui d 
f or m ulati o n at a G M P 
ma n ufact uri n g facilit y .
S R S D
I B
I B
I B
C urre nt/ F or mer 
N a me(s) or Ali as(es)
N A
N A
N A
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
St u d y Ar m(s)
A r m  Title
C o h ort 1
C o h ort 2
A r m  T y pe
E x peri me ntal
E x peri me ntal
A r m  Descri pti o n
Oral d ose of 1 0 0 m g P F -0 7 2 2 0 0 6 0
c o ntai ni n g  
n Ci [ 1 4C] ([1 4C] P F -
0 7 2 2 0 0 6 0) w ill be a d mi nistere d as a n
e xte m p ora ne o usl y pre pare d li q ui d
f or m ulati o n.
U nla bele d oral d ose of P F -0 7 2 2 0 0 6 0, 
1 0 0 m g will be a d mi nistere d as a n 
e xte m p ora ne o usl y pre pare d li q ui d 
f or m ulati o n. Ap pr o xi matel y 2 h o ur s
after t he a d mi nistrati o n of t he u nla bele d 
oral d ose, a si n gle d ose of 
μ g 
P F -0 7 2 2 0 0 6 0 c o ntai ni n g 
n Ci [ 1 4C] 
([1 4C] P F -0 7 2 2 0 0 6 0) w ill be 
a d mi nistere d I V, as a n i nf usi o n o ver 
a p pr o xi matel y 3 0 mi n utes
Ass oci ate d I nter ve nti o n 
L a bels
[1 4C] P F -0 7 2 2 0 0 6 0
P F -0 7 2 2 0 0 6 0, [ 1 4C] P F -0 7 2 2 0 0 6 0
F or C o h ort 1, [ 1 4C] P F - 0 7 2 2 0 0 6 0 i n vesti gati o nal pr o d uct f or oral a d mi nistrati o n will be 
s u p plie d b y Pfizer as b ul k A PI a n d, w here necessar y, b ul k e xci pie nts f or t he e xte m p ora ne o us 
pre parati o n of a n oral s us pe nsi o n at t he cli nic a n d will be prese nte d t o partici pa nts i n 
i n di vi d ual d osi n g c o ntai ners at t he C R U. 
F or C o h ort 2, u nla bele d P F - 0 7 2 2 0 0 6 0 i n vesti gati o nal pr o d uct f or oral a d mi nistrati o n will be 
s u p plie d b y Pfizer as b ul k A PI a n d, w here necessar y, b ulk e xci pie nts f or t he e xte m p ora ne o us 
pre parati o n of a n oral s us pe nsi o n at t he cli nic a n d will be prese nte d t o partici pa nts i n 
i n di vi d ual d osi n g c o ntai ners at t he C R U. 
I n a d diti o n, [1 4C] P F -0 7 2 2 0 0 6 0 i n vesti gati o nal pr o d uct will als o be s u p plie d b y  Pfizer as a 
b ul k p o w der f or pre parati o n of a n I V s ol uti o n of [1 4C] P F -0 7 2 2 0 0 6 0 at a G M P ma n ufact uri n g 
facilit y.
T he fi nal pr o d uct c o m p ositi o n s a n d prese ntati o n will be detaile d i n a se parate T A f or t he I V 
dr u g pr o d uct a n d E D R f or t he oral dr u g pr o d uct s.
6. 1. 1. A d mi nistr ati o n
I n C o h ort 1, a n oral d ose of a n e xte m p ora ne o usl y pre pare d oral s us pe nsi o n of 
[1 4C] P F - 0 7 2 2 0 0 6 0 1 0 0 m g i n 1 0 0 m L of 0. 5 % ( w/ v) met h ylcell ul ose i n sterile water will be 
a d mi nistere d o n Da y  1.
I n C o h ort 2, a n oral d ose of a n e xte m p ora ne o usl y pr e pare d oral s us pe nsi o n of u nla bele d 
P F - 0 7 2 2 0 0 6 0 10 0 m g i n 1 0 0 m L of 0. 5 % ( w/ v) met h ylcell ul ose i n sterile water will be 
a d mi nistere d a p pr o xi matel y 2 h o urs bef ore start of a n I V i nf usi o n of [ 1 4C] P F - 0 7 2 2 0 0 6 0
µ g i n 
m L  of 1 0 µ g/ m L P F-0 7 2 2 0 0 6 0 i n 
o n 
D a y 1.
 
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, all partici pa nts will be re q uire d 
t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P , p ulse rate , a n d E C G 
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 o n Da y  1.
[1 4C] P F -0 7 2 2 0 0 6 0 ( 1 0 0 m g d ose; 
n Ci ; C o h ort 1): F oll o wi n g an o ver ni g ht fast of at 
least 1 0 h o urs, partici pa nt s will recei ve i n vesti gati o nal pr o d uct at a p pr o xi matel y 0 8 0 0 h o urs 
( pl us or mi nus 2 h o urs). D osi n g will i n v ol ve a d mi nistrati o n of m ulti ple ri nses of t he d osi n g 
c o ntai ner, a n d a n assess me nt of t he resi d ual ra di oacti vit y  o n t he d osi n g c o ntai ner will be 
re q uire d t o be assesse d a n d d oc u me nte d i n t he st u d y C R F. I n vesti gat or site pers o n nel will 
a d mi nister i n vesti gati o nal pr o d uct acc or di n g t o t he E D R .
U nl a bele d P F - 0 7 2 2 0 0 6 0 ( 1 0 0 m g d ose ; C o h ort 2 ): F oll o wi n g an o ver ni g ht fast of at least 
1 0 h o urs , partici pa nt s will recei ve i n vesti gati o nal pr o d uct 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). I n vesti gat or site pers o n nel will a d mi nister i n vesti gati o nal pr o d uct 
acc or di n g t o t he E D R .
[1 4C] P F - 0 7 2 2 0 0 6 0 (
µ g d ose;
n Ci ; C o h ort 2): 1 0 m L of a n I V s ol uti o n of 
[1 4C ]P F - 0 7 2 2 0 0 6 0 will be a d mi nistere d i ntra ve n o usl y o ver 3 0 mi n as a c o nti n u o us i nf usi o n 
t hr o u g h a n i nf usi o n li ne starti n g 2 h o urs after a d mi nistrati o n of t he oral d ose. A d mi nistrati o n 
of [ 1 4C] P F - 0 7 2 2 0 0 6 0 s ol uti o n will be perf or me d b y q ualifie d i n vesti gat or site pers o n nel (i n 
acc or da nce wit h l ocal re g ulati o ns a n d la ws). F urt her details o n a d mi nistrati o n will be 
o utli ne d i n t he S AI .
I n b ot h c o h orts , eac h partici pa nt will rec or d t he taste assess me nt at ti me d i nter vals of 0 MI N 
(ie, as s o o n as practically p ossi ble b ut wit hi n 1 mi n ute p ost c o m pleti o n of d osi n g ) as 
s pecifie d i n t he S AI, a n d at 5, 1 0, a n d 2 0 mi n utes after d osi n g usi n g t he s p o ns or pr o vi de d 
Taste Assess me nt Q uesti o n naire.
A d mi nistrati o n of la bele d a n d u nla bele d P F- 0 7 2 2 0 0 6 0 via oral a n d i ntra ve n o us d osi n g r o utes 
will be perf or me d b y q ualifie d i n vesti gat or si te pers o n nel (i n acc or da nce wit h l ocal 
re g ulati o ns a n d la ws). Please refer t o t he S AI f or f urt her details.
A d mi nistrati o n of st u d y  i nter ve nti o n(s) at t he site will be perf or me d b y a n a p pr o priatel y 
q ualifie d a n d trai ne d me m ber of t he st u d y staff as all o we d b y l ocal, state, a n d i nstit uti o nal 
g ui da nce. 
F oll o wi n g a d mi nistrati o n of st u d y i nter ve nti o n(s) at t he site, partici pa nts will be o bser ve d f or 
3 0 mi n 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 dy 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. 
 
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ocatio 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 usl y 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 dy i nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, as s o o n as p ossi ble. 
O nce a n e xc ursi o n is i de ntifie d, t he st u d y  i nter ve nti o n m ust be q uara nti ne d a n d n ot use d 
u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  i nter ve nti o n. S pecific details re gar di n g 
t he e xc ursi o n defi niti o n a n d i nf or mati o n t o re p ort f or eac h e xc ursi o n will be pr o vi de d t o 
t he site i n t he C R U l ocal/site pr oce d ures.
5.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge c o n diti o ns 
state d o n t he la bel.
6.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners.
7.
T he i n vesti gat or, i nstit uti o n, hea d of t he me dical i nstit uti o n ( w here a p plica b le), or 
a ut h orize d site staff is res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y, rec o nciliati o n, 
a n d rec or d mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds) , s uc h as 
t he IP A L or s p o ns or -a p pr o ve d e q ui vale nt . All st u d y  i nter ve nti o ns will be acc o u nte d f or 
usi n g a st u d y i nter ve nti o n acc o u nta bilit y f or m/rec or d.
8.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  i nter ve nti o ns 
are pr o vi de d i n t he C R U’s l ocal/site pr oce d ures . All destr ucti o n m ust be a de q uatel y 
d oc u me nte d. If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or site, t he 
i n vesti gat or m ust e ns ure t hat t he materials are destr o ye d i n c o m plia nce wit h a p plica ble 
e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns pr o vi de d b y  
Pfizer.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y t he s p o ns or w it 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 vi der, 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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.
[1 4C] P F - 0 7 2 2 0 0 6 0 a n d u nla bele d P F - 0 7 2 2 0 0 6 0 oral s us pe nsi o n will be pre pare d i n t he C R U 
b y  2 trai ne d pers o n nel . 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.
[1 4C ] P F- 0 7 2 2 0 0 6 0 s ol uti o n f or t he I V a d mi nistrati o n will be pre pare d at a G M P facilit y b y 
2 o perat ors. Details of d ose pre parati o n will be gi ve n i n a se parate tec h nical a gree me nt. T he 
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 la beli n g re q uire me nts.
O nl y  q ualifie d pers o n nel w h o are fa miliar wit h pr oce d ures t hat mi ni mize u n d ue e x p os ure t o 
t he msel ves a n d t o t he e n vir o n me nt s h o ul d u n derta ke t he pre parati o n, ha n dli n g, a n d safe 
dis p osal of I ps. Left o ver c o ntai ners f oll o wi n g b ot h oral a n d I V a d mi nistrati o n, i ncl u di n g 
t u bi n g use d f or i nf usi o n, s h o ul d be retai ne d f or assess me nt of ra di oacti vit y if nee de d. 
6. 3. Assi g n me nt t o St u d y I nter ve nti o n
T he i n vesti gat or’s k n o wle d ge of t he treat me nt s h o ul d n ot i nfl ue nce t he decisi o n t o e nr oll a 
partic ular partici pa nt or affect t he or der i n w hic h partici pa nt s are e nr olle d.
T he i n vesti gat or will assi g n partici pa nt n u m bers t o t he partici pa nt s as t he y are scree ne d f or 
t he st u d y. Pfizer will pr o vi de a ra n d o mizati o n sc he d ule to t he i n vesti gat or t o all ocate 
partici pa nts t o c o h orts a n d, i n acc or da nce wit h t he ra n d o mizati o n (all ocati o n) n u m bers, t he 
partici pa nt will recei ve t he st u d y  treat me nt re gi me n assi g ne d t o t he c orres p o n di n g 
ra n d o mizati o n (all ocati o n) n u m ber.
6. 4. Bli n di n g
T his is a n o pe n-la bel st u d y. 
6. 4. 1. Bli n di n g of t he S p o ns or
As t his is a n o pe n -la bel st u d y, t he s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g 
t he c o urse of t he st u d y f or t he p ur p ose of safety assess me nt, facilitati n g P K/ P D m o deli n g, 
a n d/ or s u p p orti n g cli ni cal de vel o p me nt.
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n partici pa nts are d ose d at t he site, t he y  will recei ve st u d y i nter ve nti o n directl y fr o m t he 
i n vesti gat or or desi g nee, u n der me dical s u per visi o n. T he date a n d ti me of eac h d ose 
a d mi nistere d i n t he C R U 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 xa mi ne eac h partici pa nt’s m o ut h t o e ns ure t hat 
t he st u d y i nter ve nti o n was i n geste d.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T he site will c o m plete t he re q uire d d osa ge Pre parati o n Rec or d l ocate d i n t he E D R . T he use 
of t he Pre parati o n Rec or d is preferre d , b ut i t d oes n ot precl u de t he use of a n e xisti n g 
a p pr o priate cli nical site d oc u me ntati o n s y ste m. T he e xisti n g cli nical site’s d oc u me ntati o n 
s yste m s h o ul d ca pt ure all perti ne nt/re q uire d i nf or mati o n o n t he pre parati o n a n d 
a d mi nistrati o n of t he d ose. T his ma y be use d i n place of t he Pre parati o n Rec or d after 
a p pr o val fr o m t he s p o ns or a n d/ or desi g nee.
6. 6. D ose M o dific ati o n
N o d ose m o dificati o n is a ntici pate d.
6. 7. C o nti n ue d Access t o St u d y 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 2 2 0 0 6 0 greater t ha n 
m g 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 P F- 0 7 2 2 0 0 6 0 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/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 of t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E.
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y  
i nter ve nti o n. 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 by t he s p o ns or. Ac eta mi n o p he n/ paraceta m ol ma y be use d at d oses of 
≤1 g/ da y .
As P F -0 7 2 2 0 0 6 0 is pri maril y  meta b olize d b y U G T 2 B 7 a n d C Y P 3 A 4, as deter mi ne d i n i n 
vitr o st u dies, c o nc o mita nt use of a n y me dicati o ns or s u bsta nces t hat are str o n g i n d ucers a n d 
i n hi bit ors of U G T 2 B 7 a nd C Y P 3 A 4 are pr o hi bite d wit hi n 1 8 da y s ( u p t o 2 8 da ys) a n d 2 8 
da y s pri or t o d osi n g of st u d y  i nter ve nti o n res pecti vel y a n d wit hi n 4 da ys after t he si n gle oral 
d ose of P F - 0 7 2 2 0 0 6 0. Per i n vitr o st u dies, P F-0 7 2 2 0 0 6 0 is als o i n dicate d t o be a 
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
, t h us, c o nc o mita nt me dicati o ns t hat are 
se nsiti ve s u bstrates f or t hese e nz ymes s h o ul d be use d wit h ca uti o n.
Aci d re d uci n g a ge nts ma y 
P F -0 7 2 2 0 0 6 0 a bs or pti o n a n d s ys te mic e x p os ure. Use of 
 is pr o hi bite d d uri n g t he st u d y  a n d 2 8 d a y s pri or t o d osi n g of st u d y 
i nter ve nti o n. Ot her aci d re d uci n g a ge nts i ncl u di n g H 2-rece pt or a ntag o nists or l ocal a ntaci ds 
s h o ul d be was he d o ut f or at least 7 d a y s or 5 half -li ves, w hic he ver is l o n ger, bef ore t he 
d osi n g of st u d y  i nter ve nti o n a n d are pr o hi bite d wit hi n 5 da y s after t he d osi n g. 
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, r o ute of a d mi nistrati o n, 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
As t his is a si n gle d ose st u d y , it s h o ul d be n ot a p plica ble f or t his secti o n.
7. 1. 1. P ote nti al C ases of Ac u te Ki d ne y I nj ur y
Partici pa nts e x p ose d t o I M P de m o nstrati n g tra nsie nt or s ustai ne d i ncrease i n Screat ( wit h 
decrease i n Screat -base d e G F R or e Cr C l) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter-me diate d effect r elate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
A KI m a y  be d ue t o o ne or m ore ty pes of i nj ur y, i ncl u di n g DI KI. Differe ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y c o ns ultati o n.
F oll o w -u p Assess me nts
T he partici pa nt s h o ul d ret ur n t o t he site f or e val uati o n as s o o n as p ossi ble, prefera bl y wit hi n 
4 8 h o urs of a ware ness of t he a b n or mal res ults. 
E val uati o n s h o ul d i ncl u de p h y sical e xa mi nati o n, la b orat or y tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs a n d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, an 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 Sc ys a n d 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 u ati o n descri be d i n A p pe n di x 7 .
 
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ntia te 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 
( whe n a vaila ble)
P r otei n uria
C o nfir me d pr otei n uria i ncrease (1 +
t hr o u g h 4 +)
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 
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 ou n d.
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al F r o m t he St u d y
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at t heir o w n re q uest . Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ures;
 

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

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o atte n d a re q uire d st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble. Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w - u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d;

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, t he partici pa nt will be c o nsi dere d 
t o ha ve wit h dra w n fr o m t he st 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 Pr oce d ures
T he i n ve sti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures. 
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Partici pa nt s will be scree ne d wit hi n 2 8 da y s pri or t o a 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 ollecti o ns, e g, retai ne d researc h sa m ples, 
ma y  n ot nee d t o be re peate d , as a p pr o priate.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma ke it u nfeasi ble t o perf or m t he 
test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
well -bei n g of t he partici pa nt . W he n a pr ot oc ol-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nfor me d of t hese i nci de nts i n a ti mel y  ma n ner.
If a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g n assess me nts 
(p ulse rate a n d B P) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter.
F or sa m ples bei n g c ollecte d a n d s hi p pe d , detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nts i n t his st u d y  will be less t ha n 
5 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 n y 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 nt s 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 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
me as ure me nts m a y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess a n y percei ve d safet y 
iss ues.
8. 3. 1. P h ysic al E x a mi n ati o ns
A c o m plete p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, hea d, ears, e yes, n ose, m o ut h, 
s ki n, heart a n d l u n g e xa mi nati o ns, l ym p h n o des, a n d gastr oi ntesti nal, m usc ul os keletal, a n d 
ne ur ol o gical s ys te ms. 
A brief p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of ge neral a p peara nce, 
t he res pirat or y a nd car di o vasc ular s ys te ms, a n d partici pa nt -re p orte d sy m pt o ms.
P h y sical e xa mi nati o ns ma y be c o n d ucte d b y a p hysicia n, trai ne d p h ys icia n’s assista nt, or 
n urse practiti o ner as acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets s o t hat o nl y
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
li g ht cl ot hi n g re mai ns. T he y m ust als o re m o ve t he c o nte nts of t heir p oc kets a n d re mai n still 
d uri n g meas ure me nt of wei g ht. 
P h y sical e xa mi nati o n fi n di n gs c ollecte d d uri n g t he st u d y will be c o nsi dere d s o urce rec or d 
a n d will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. A n y u nt o war d p h ys ical 
e xa mi nati o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 2. Vit al Si g ns
8. 3. 2. 1. Bl o o d Press ure a n d P ulse R ate
S u pi ne B P will be meas ure d wit h t he partici pa nt ’s ar m s u p p orte d at t he le vel of t he heart, a n d 
rec or de d t o t he nearest m m H g after a p pr o xi matel y 5 mi n utes of rest . T he sa me ar m 
( prefera bly t he d o mi na nt ar m) will be use d t hr o u g h o ut t he st u d y. B P s h o ul d n ot be ta ke n 
fr o m t he ar m wit h a n i ntra ve n o us i nf usi o n. Partici pa nt s s h o ul d be i nstr ucte d n ot t o s pea k 
d uri n g meas u re me nts. 
T he sa me pr o perl y size d a n d cali brate d B P c uff will be use d t o meas ure B P eac h ti me. T he 
use of a n a ut o mate d de vice f or meas uri n g B P a n d p ulse rate is acce pta ble; h o we ver, w he n 
d o ne ma n uall y, p ulse rate will be meas ure d i n t he brac hial/ra dial art er y f or at least 
3 0 sec o n ds. W he n t he ti mi n g of t hese meas ure me nts c oi nci des wit h a bl o o d c ollecti o n, B P 
a n d p ulse rate s h o ul d be o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n.
A d diti o nal c ollecti o n ti mes, or c ha n ges t o c ollecti o n ti mes, of B P a n d p ulse rate will be 
per mitte d, as necessar y, t o e ns ure a p pr o priate c ollecti o n of safet y  data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 3. Electr oc ar di o gr a ms
Sta n dar d 1 2-l ea d EC Gs will be c ollecte d at ti mes s pecifie d i n t he S o A secti o n of t his
pr ot oc ol usi n g a n E C G s yste m t hat a ut o maticall y calc ulates t he H R a n d meas ures P R, Q T, 
Q Tc F, a n d Q R S i nter vals. All sc he d ule d E C Gs s h o ul d be perf or me d after t he partici pa nt has 
reste d q uietly f or at least 5 mi n utes i n a s u pi ne p ositi o n. 
T o e ns ure safet y of t he partici pa nt s, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o baseli ne meas ure me nts. A d diti o nal E C G m o nit ori n g will occ ur if a) a 
p ost d ose Q Tc F i nter val is i ncrease d b y ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a ny sc he d ule d E C G. If eit her of t hese c o n diti o ns occ urs, 
t he n 2 a d diti o nal E C Gs will be c ollecte d a p pr o xi matel y  2 t o 4 mi n utes a part t o c o nfir m t he 
ori gi nal meas ure me nt. If t he Q 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 urly u ntil Q Tc val ues fr o m 
2 s uccessi ve E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat meas ure me nt.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
If a) a p ost d ose Q Tc F i nter val re mai ns ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a ny sc he d ule d E C G f or greater t ha n 4 h o urs ( or s o o ner , at 
t he discreti o n of t he i n vesti gat or); or c) Q Tc F val ue get pr o gressi vel y  l o n ger, t he partici pa nt
s h o ul d u n der g o c o nti n u o us E C G m o nit ori n g. A car di ol o gist s h o ul d be c o ns ulte d if Q TcF
val ues d o n ot ret ur n t o less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
I n s o me cases, it ma y be a p pro 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. 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 olre 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 cli nicall y si g nifica nt a n d a b n or mal d uri n g 
partici pati o n i n t he st u d y  or wit hi n 4 8 h o urs after t he last d ose of st u d y i nter ve nti o n s h o ul d 
be re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l o n ger c o nsi dere d cli nicall y 
si g nifica nt by t he i n vesti gat or or st u d y me dical m o nit or.
If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he i n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d an 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 nt s t o recei ve st u d y 
i nter ve nti o n.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 4. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A E s ma y arise fr o m sy m pt o ms or ot her c o m plai nts re p orte d t o t he i n vest i gat or b y t he 
partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he partici pa nt ’s le gall y 
a ut h orize d re prese ntati ve), or t he y  ma y arise fr o m cli nical fi n di n gs of t he in vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, e tc).
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 (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 pecif ic 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 h e st u d y i nter ve nti o n.
F oll o w -u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut t he acti ve c ollecti o n peri o d a n d u ntil t he 
A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or.
W he n a cli nicall y i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
F or partici pa nts w h o are scree n fai l 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 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 E s or S A Es 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 n y S A E, 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 0
i 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 partici 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 rela te 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 E s a nd 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 .
8. 4. 2.
Met h o d of Detecti n g A E s a n d S A Es
T he met h o d of rec or di n g, e val uati n g, a n d assessi n g ca usalit y  of AEs a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A E s a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 4. 3. F oll o w - 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 d efi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi nati o n of 
p oss i 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 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ur t her i nf or mati o n o n f oll o w-u p pr oce d ures is pr o vi de d i n A p pe n di x 3 .
8. 4. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of an S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war d t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I RBs / Ecs, a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 4. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure, occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or SA E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o vi ders, fa mil y me m bers, a n d ot hers w h o ma y be e x p ose d. A n 
e n vir o n me ntal e x p os ure ma y  i ncl u de E D P, E D B , a n d occ u pati o nal e x p os ure.
A n y  s uc h ex p os ure s t o t he st u d y i nter ve nti o n u n der st u d y  are re p orta ble t o Pfizer Safet y 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
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 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 partic i 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 v i 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 .
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n c o ntact t he n i nse mi nates his fe male 
part ner p ri 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’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 u ntil 2 8 da y s after t he last d ose.

If E D P occ urs i n t he setti n g of e n vir o n mental e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m 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 pr e g na nc y u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w-u p t o t he i nitial re p ort. In t he case of a li ve birt h, t he str uct ural i nte grit y  of t he ne o nate 
ca n be assesse d at t he ti me of birt h. I n t he e ve nt of a ter mi nati o n, t he reas o n(s) f or 
ter mi nati o n s h o ul d be s pecifie d a n d, if cli nically p ossi ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr oss vis ual i ns pecti o n ( u nless pre -pr oce d ure test 
fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o maly a n d t he fi n di n gs are re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. If t he o utc o me of t he pre g na nc y meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
de mise, ne o natal deat h, or c o n ge nita l a n o maly 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 AEs f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n s h o ul d be re p orte d 
as a n S A E ;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es. I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d 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 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
preter m i nfa nts t o i de ntif y de vel o p me ntal dela y s). In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici pa nt wit h t he Pre g na nt Part ner Release of I nf or mati o n 
F or m t o deli ver t o his part ner. T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t hat 
t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his 
part ner.
8. 4. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n E D B occ urs if:

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 mental e x p os ure). A n e xa m ple of 
e n vir o n me ntal E D B is a fe male fa mily me m ber or healt hcare pr o vi der w h o re p orts 
t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y 
i n gesti o n, i n halati o n, or s ki n c o ntact. 
T he i n vesti gat or m ust re p ort E D B t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nf or mati o n m ust be re p 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 nfor mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y , 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 pecificall y a p pr o ve d f or use i n 
breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or d a nce wit h a ut h orize d use. 
H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d 
t o get her wit h t he E D B .
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 ot Q u alif yi n g as A E s 
or S A Es
N ot a p plica ble.
8. 4. 8. A d verse E ve nts of S peci al I nterest
N ot a p plica ble.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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.
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 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 or i nc orrect c o m bi nati o n of ta blet d ose 
stre n gt hs
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 o f t he A E pa ge a n d, if 
a p plica ble, a n y ass ociate d seri o us a n d n o nseri o us A E(s), are rec or de d o n t he A E pa ge of t he 
C R F .
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs .
Me dicati o n err ors s h o ul d be re p orte d t o Pfize r 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 5. P h ar m ac o ki netics 
8. 5. 1. Pl as m a f or P h ar m ac o ki netic A n al ysis of T ot al 1 4C R a di o acti vit y, P F - 0 7 2 2 0 0 6 0, 
[1 4C]- P F - 0 72 2 0 0 6 0 a n d Met a b olic Pr ofili n g
Bl o o d sa m ples of a p pr o xi matel y  8 m L , will be c ollecte d i nt o a p pr o priatel y la bele d t u bes 
c o ntai ni n g K 2E D T A f or meas ure me nt of t otal 1 4C ra di oacti vit y b y A M S a n d P F -0 7 2 2 0 0 6 0 b y  
L C M S i n C o h ort 1 as s pecifie d i n t he S o A . T he 8 m L scree ni n g bl o o d sa m ple will be use d t o 
assess 1 4C t otal ra di oacti vit y  f or scree ni n g o nl y a n d will be st ore d f or p ote ntial use as t he 
dil ue nt f or p ost -d ose A M S sa m ples. Bl o o d sa m ples of a p pr o xi matel y  1 0 m L , will be 
c ollecte d i nt o a p pr o priately la bele d t u bes c o ntai ni n g K 2E D T A f or meta b olite i de ntificati o n i n 
C o h ort 1 as s pecifie d i n t he S o A . 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 
mi ni m u m of 1. 5 m L  plas ma, will be c ollecte d f or meas ure me nt of P F -0 7 2 2 0 0 6 0 b y L C M S i n 
C o h ort 2 as s pecifie d i n t he S o A . 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 
mi ni m u m of 1. 5 m L  plas ma, will be c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of 
[1 4C] P F -0 7 2 2 0 0 6 0 b y  A M S i n C o h ort 2 as s pecifie d i n t he S o A . A 8 m L  scree ni n g sa m ple 
c ollecti o n will be use d t o assess [ 1 4C] P F -0 7 2 2 0 0 6 0 f or scree ni n g o nl y a n d will be st ore d f or 
p ote ntial use as t he dil ue nt f or p ost- d ose A M S sa m ples. Bl o o d sa m ples of a p pr o xi matel y  
1 0 m L , will be c ollecte d i nt o a p pr o priately la bele d t u bes c o ntai ni n g K 2E D T A f or c o nti n ge nt 
use of meta b o lites i de ntificati o n i n C o h ort 2 as s pecifie d i n t he S o A . I nstr ucti o ns f or t he 
c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he la b orat or y  ma n ual or b y 
t he s p o ns or. T he act ual date a n d ti me ( 2 4 h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
T he act ual ti mes ma y  c ha n ge, b ut t he n u m ber of sa m ples will re mai n t he sa me. All eff orts 
will be ma de t o o btai n t he sa m 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 (e g, wit hi n 6 mi n utes of a 6 0 mi n ute sa m ple) 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 data c ollecti o n t o ol (e g, C R F). C ollecti o n of sa m ples m ore t ha n 
1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y fr o m t he n o mi nal ti me 
relati ve t o d osi n g will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he 
c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d data c ollecti o n t o ol (e g, C R F). If a sc he d ule d 
bl o o d sa m ple c ollecti o n ca n n ot be c o m plete d f or a n y  reas o n, t he misse d sa m ple ti me ma y be 
re-sc he d ule d wit h a gree me nt of t he cli nical i n vesti gat or, partici pa nt, a n d s p o ns or.
Sa m ples will be use d t o e val uate t he P K of total 1 4C ra di oacti vit y, P F-0 7 2 2 0 0 6 0 , 
[1 4C] P F - 0 7 2 2 0 0 6 0 a n d m eta b olic p r ofili n g. Sa m ples c ollecte d f or a nal y ses of P F- 0 7 2 2 0 0 6 0, 
t otal 1 4C ra di oacti vit y, a n d 1 4C P F- 0 7 2 2 0 0 6 0 plas ma c o nce ntrati o n ma y  als o be use d t o 
e val uate safet y or efficac y as pects relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y, f or 
meta b olite i de ntificati o n a n d/ or e val uati o n of a bi oa nal yt ical met h o d, or f or ot her i nter nal 
e x pl orat or y p ur p oses.
T he plas ma P K sa m ples c ollecte d f or t he meas ure me nt of [1 4C] P F -0 7 2 2 0 0 6 0 ( b y  H P LC-
A M S) or T otal 1 4C ra di oacti vit y ( by A M S) or P F - 0 7 2 2 0 0 6 0 (b y L C M S/ M S ) ma y  be use d f or 
t he meas ure me nt of T otal 1 4C ra di oacti vit y, [1 4C]- P F - 0 7 2 2 0 0 6 0 or meta b olite pr ofili n g at 
S p o ns or’s discreti o n, as nee de d. 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 2 2 0 0 6 0 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. T otal 
1 4C meas ure me nts, [1 4C] P F - 0 7 2 2 0 0 6 0 a n d meta b olic pr ofili n g will be perf or me d usi n g a 
separate a p pr o priate met h o d base d o n A M S pri nci ples a n d met h o d ol o g y .
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 oc e 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 nati o n as t o w het her sa m ple 
i ntegrit y has bee n c o m pr o mise d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstitute a pr ot oc ol a me n d me nt. T he I R 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.
At t he discreti o n of t he S p o ns or, o ne or m ore pla n ne d a nal ys es ma y n ot be c o n d ucte d if 
dee me d u n nece ssar y b y t he S p o ns or base d o n e mer gi n g data.
8. 5. 2. Uri ne a n d Feces f or A n al ysis of P F - 0 7 2 2 0 0 6 0, T ot al 1 4C R a di o acti vit y a n d 
Met a b olic Pr ofili n g
Uri ne will be c ollecte d f or deter mi nati o n of P F -0 7 2 2 0 0 6 0 , t otal 1 4C ra di oacti vit y  a n d 
meta b olite pr ofili n g i n C o h ort 1 , a n d will be c ollecte d f or deter mi nati o n of t otal 1 4C 
ra di oacti vit y a n d meta b olite pr ofili n g (as nee de d) i n C o h ort 2, res pecti vel y as s pecifie d i n t he 
S o A . T he partici pa nts i n C o h ort 1 a n d 2 will f orce v oi d bef or e oral d osi n g a n d bef ore I V 
d osi n g , res pecti vely . Pri or t o d osi n g o n Da y 1 ( wit hi n 2 4 h o urs), eac h partici pa nt m ust e m pt y  
his uri nar y  bla d der; a n ali q u ot fr o m t his uri ne will ser ve as t he “ uri ne bla n k”. T he details 
re gar di n g t he c ollecti o n, pr ocessi n g, st ora ge a n d s hi p pi n g of t he uri ne sa m ples will be 
pr o vi de d i n t he la b ma n ual. 
Feces will als o be c ollecte d f or deter mi nati o n of t otal 1 4C ra di oacti vit y  a n d meta b olite 
pr ofili n g i n b ot h peri o ds as s pecifie d i n t he S o A . A pre-d ose fecal sa m ple is re q uire d wit hi n 
4 8 h o urs pri or t o d osi n g [ 1 4C] P F - 0 7 2 2 0 0 6 0 i n b ot h c o h orts . If m ulti ple baseli ne fecal sa m ples 
are c ollecte d f or a partici pa nt, t he o ne cl osest t o d osi n g will be use d as t he baseli ne sa m ple 
a n d all ot her fecal sam ples will be discar de d.
Details of t he c ollecti o n of ali q u ots, v ol u me, pr ocessi n g, st ora ge a n d s hi p pi n g of t he uri ne 
a n d feces sa m ples will be pr o vi de d i n t he la b ma n ual. 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
F or C o h ort 1, sa m ples c ollecte d f or meas ure me nt of uri ne c o nce ntrati o ns of P F - 0 7 2 2 0 0 6 0
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.
T otal 1 4C meas ure me nts a n d meta b olic pr ofili n g of uri ne sa m ples will be perf or me d usi n g a 
se parate a p pr o priate met h o d base d o n A M S pri nci ples a n d met h o d ol o g y. A n d t otal 
1 4C meas ure me nts a n d meta b olic pr ofili n g of feces sa m ples will be perf or me d usi n g a 
se parate a p pr o priate met h o d base d o n A M S pri nci ples a n d met h o d ol o g y. F or C o h ort 2, 
a nal y sis of meta b olic pr ofili n g i n uri ne a n d feces sa m ples will be a nal yz e d as nee de d f or 
c o nti n ge nc y as descri be d b y t he la b ma n ual. 
Sa m ples will be use d t o e val uate t he rec o ver y of total 1 4C ra di oacti vit y, P F- 0 7 2 2 0 0 6 0, 
[1 4C ]P F - 0 7 2 2 0 0 6 0 a n d m eta b olic p r ofili n g. Sa m ples c ollecte d f or t hese a nal yses ma y als o be 
use d t o e val uate safet y or efficac y as pects relate d t o c o ncer ns arisi n g d uri n g or after t he 
st u d y, f or meta b olite i de ntificati o n a n d/ or e val uati o n of a bi oa nal yt ical met h o d, or f or ot her 
i nter nal ex pl orat or y  p ur p oses.
At t he discreti o n of t he S p o ns or, o ne or m ore pla n ne d a nal ys es ma y n ot be c o n d ucte d if 
dee me d u n necessar y  b y t he S p o ns or base d o n e mer gi n g data.
8. 5. 3. E mesis (If a n y)
If e mesis occ urs wit hi n
hrs after d osi n g, t he n t he v o mit us m ust be c oll ecte d i n f ull a n d 
st ore d f or a ra di oacti vit y assess me nt. F or e mesis t hat occ urs after  
h o urs u p t o  
h o urs 
p ost d ose, sa m ples will be c ollecte d i n f ull a n d st ore d f or p ote ntial refle x testi n g of 
ra di oacti vit y rec o vere d. All e mesis i ncl u di n g a n y s wa b bi n g, c o nta mi nate d li ne ns a n d facial 
tiss ues use d t o c ollect b o dil y disc har ge; e g, n ose blee di n g clea n u p tiss ue a n d a n y e mesis 
relate d clea n u p is t o be c ollecte d. T he ti me a n d date of a n y v o miti n g e ve nt wit hi n t he first 
 
h o urs p ost -d ose m ust be rec or de d .Part ici pa nts w h o e x perie nce e mesis f oll o wi n g oral d osi n g 
will n ot necessaril y be e xcl u de d fr o m a nal ys is (see Secti o n 9. 3 f or a d diti o nal details o n 
e val ua ble partici pa nts).
8. 5. 4. A n al ysis of D osi n g S ol uti o n a n d Deter mi n ati o n of A d mi nistere d D ose
I n t he I V c o h ort, t he [1 4C]- P F - 0 7 2 2 0 0 6 0 d osi n g s ol uti o n will be a nal y ze d f or t otal 1 4C usi n g 
L S C. Detaile d st ora ge a n d s hi p me nt pr oce d ures will be pr o vi de d i n t he S AI a n d la b orat or y 
ma n ual t o t he cli nical site pri or t o t he start of t he cli nical trial.
F or oral a d mi nistrati o n of [1 4C]- P F - 0 7 2 2 0 0 6 0, t he wei g ht of [1 4C ]-P F - 0 7 2 2 0 0 6 0 A PI  p o w der 
wei g he d i nt o eac h d osi n g b ottle will be use d i n c o nj u ncti o n wit h t he s pecific acti vit y of t he 
A PI t o deter mi ne t he e xact d ose a d mi nistere d. Resi d ual ra di oacti vit y  i n t he oral d osi n g 
c o ntai ner will be re q uire d t o be assesse d i n C o h ort 1 a n d d oc u me nte d i n t he st u d y  C R F.
F or I V a d mi nistrati o n of [1 4C]- P F - 0 7 2 2 0 0 6 0, t he d ose v ol u me a d mi nistere d will be 
c o ntr olle d usi n g pre -cali brate d i nf usi o n p u m ps . The v ol u me of I V d ose (c o m p ute d usi n g 
wei g ht of t he d osi n g s ol uti o n a d mi nistere d a n d t he de nsit y of t he d osi n g s ol uti o ns), a n d 
c o nce ntrati o n of P F- 0 7 2 2 0 0 6 0 a n d ra di oacti vit y  i n d osi n g s ol uti o n will be use d t o deter mi ne 
t he e xact d ose a d mi nistere d f or eac h partici pa nt.
T he act ual d oses will be rec or de d i n t he C R F a n d will be use d f or P K a nal ysis.
 
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 i nt o plastic K 2E D T A t u bes, as 
defi ne d i n t he S o A . T he D N A sa m ple will be a nal yze d f or t he p ur p ose of assessi n g t he 
i m pact of allelic varia nts of ge nes e nc o di n g dr u g meta b olizi n g e nz ymes a n d tra ns p orters 
i ncl u di n g, b ut n ot li mite d t o, C Y P 3 A a n d U G T 2 B 7 o n t he A D M E of t he P F - 0 7 2 2 0 0 6 0. 
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 
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 ye ars after C S R 
fi nalizati o n. In 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 re q 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 s p o ns or -i de ntifie d st u d y-s pecific 
ce ntral La b orat or y Ma n ual.
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 ns tr 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 viati o n.
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
C ollecti o n of retai ne d researc h sa m p les is n ot a p plica ble t o t his st u d y. 
8. 7. Bi o m ar kers
Bi o mar kers are n ot e val uate d i n t his st u d y .
8. 8. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y .
8. 9. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n a n d h ealt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
8. 1 0. T aste Assess me nt
T he se ns or y  attri b utes of P F- 0 7 2 2 00 6 0 will be e val uate d b y  eac h partici pa nt usi n g a Taste 
Assess me nt Q uesti o n naire (A p pe n di x 9 ) f oll o wi n g oral d osi n g i n b ot h c o h orts. Eac h 
partici pa nt will c o m plete t he Taste Assess me nt S ur ve y  i m me diately f oll o wi n g d osi n g 
( wit hi n 1 mi n) pl us at 5, 1 0, a n d 2 0 mi n utes p ost oral a d mi nistrati o n of [1 4C] P F - 0 7 2 2 0 0 6 0 or 
P F - 0 72 2 0 0 6 0 oral s us pe nsi o n.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d f urt her detaile d i n t he S A P, w hic h will be mai ntai ne d b y  t he s p o ns or. 
T he S A P ma y  m o dif y w hat is o utli ne d i n t he pr ot oc ol w here a p pr o priate; h o we ver, a n y  maj or 
m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot heses
T here are n o statistical h yp ot heses f or t his st u d y .
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d/ All ocate d t o 
st u d y i nter ve nti o n 
" E nr olle d" mea ns a partici pa nt's a gree me nt t o partici pate i n a 
cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess a n d scree ni n g. P ote ntial partici pa nts w h o are scree ne d 
f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y, b ut d o 
n ot partici pate i n t he st u d y, are n ot c o nsi dere d e nr olle d, u nless 
ot her wise s pecifie d b y t he pr ot oc ol. A partici pa nt will be 
c o nsi dere d e nr o lle d if t he i nf or me d c o nse nt is n ot wit h dra w n 
pri or t o partici pati n g i n a n y  st u d y acti vit y after scree ni n g.
Mass bala nce a nal ys is 
set 
I n C o h ort 1, t he mass bala nce p o p ulati o n a nal ys is set will be 
defi ne d b y e val ua ble partici pa nts w h o ha ve recei ve d 1 d ose of 
[1 4C] P F - 0 7 2 2 0 0 6 0 a n d w h o ha ve c o m plete d t otal ra di oacti vit y 
c o nce ntrati o n ( uri nar y a n d fecal) data a n d w h o ha d n o pr ot oc ol 
de viati o ns t hat ma y  ha ve affecte d t he mass bala nce a nalys is. 
F urt her details w hat partici pa nts will be q ualifie d as e val ua ble 
par tici pa nts will be pr o vi de d i n t he S A P, h o we ver, it s h o ul d be 
n ote d t hat v o miti n g wit hi n  
h o urs p ost oral d ose or 
si g nifica nt resi d ual acti vit y i n t he d osi n g c o ntai ner d oes n ot 
necessaril y  precl u de p artici pa nt s fr o m bei n g e val ua ble.
P K C o nce ntrati o n
T he P K c o nce ntrati o n p o p ulati o n f or P F -0 7 2 2 0 0 6 0 is defi ne d 
as all partici pa nts d ose d wit h P F - 0 7 2 2 0 0 6 0 (i n b ot h C o h ort 1 
a n d 2), w h o ha ve at least o ne P F - 0 7 2 2 0 0 6 0 c o nce ntrati o n. 
T he P K c o nce ntrati o n p o p ulati o n f or [ 1 4C] is defi ne d as all 
partici pa nts d ose d wit h [ 1 4C] P F - 0 7 2 2 0 0 6 0 (i n b ot h C o h ort 1 
a n d 2), w h o ha ve at least o ne [ 1 4C] meas ure me nt.
T he P K c o nce ntrati o n p o p ulati o n f or [ 1 4C] P F - 0 7 2 2 0 0 6 0 is 
defi ne d as all partici pa nts d ose d wit h [ 1 4C] P F -0 7 2 2 0 0 6 0 i n 
 
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
P artici p a nt A n al ysis 
Set
Descri pti o n
C o h ort 2 , w h o ha ve at least o ne [1 4C] P F - 0 7 2 2 0 0 6 0 pla s ma 
c o nce ntrati o n meas ure me nt.
P K Para meter
T he P K para meter p o p ulati o n f or P F - 0 7 2 2 0 0 6 0 is defi ne d as 
all partici pa nts d ose d wit h P F - 0 7 2 2 0 0 6 0 (i n b ot h C o h ort 1 or 
2), w h o ha ve at least o ne esti mate d P F - 0 7 2 2 0 0 6 0 P K 
para meter of i nterest . 
T he P K para meter p o p ulati o n f or t otal [1 4C] is defi ne d as all 
partici pa nts d ose d wit h [ 1 4C] P F - 0 7 2 2 0 0 6 0 (i n b ot h C o h ort 1 or 
2) , w h o ha ve at least o ne t otal [1 4C] P K para meters of i nterest .
T he P K para meter p o p ulati o n f or [ 1 4C] P F - 0 7 2 2 0 0 6 0 is defi ne d 
as all partici pa nts d ose d wit h [ 1 4C] P F - 0 7 2 2 0 0 6 0 i n C o h ort 2, 
w h o ha ve at least o ne [ 1 4C] P F - 0 7 2 2 0 0 6 0 P K para meter of 
i nterest.
Safet y
All partici pa nts all ocate 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 dy i nter ve nti o n. Partici pa nts will be a nal yz e d 
acc or di n g t o t he pr o d uct t he y act uall y recei ve d.
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y a nalys es are p erf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data.
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal y ses of t he pri mar y a n d sec o n dar y 
e n d p oi nts.
9. 3. 1. Pri m ar y E n d p oi nts
9. 3. 1. 1.
M ass B al a nce 
T ot al R a di o acti vit y i n uri ne will be re p orte d f or C o h ort 1 a n d 2 se paratel y, as t he 
perce nta ge of t he a d mi nistere d ra di oacti vit y  e xcrete d at eac h ti me i nter val a n d as t he
c u m ulati ve t otal perce nt of d ose e xcrete d i n uri ne o ver ti me.
T ot al R a di o acti vit y i n feces will be re p orte d f or C o h ort 1 (a n d if a p plica ble f or C o h or t 2),
as t he perce nta ge of t he a d mi nistere d ra di oacti vit y e xcrete d at eac h ti me i nter val a n d as t he 
c u m ulati vet otal perce nt of d ose e xcrete d i n feces o ver ti me.
T ot al R a di o acti vit y i n v o mit us (if a n y) will be re p orte d f or C o h ort 1 o nl y , as t he 
perce nta ge of t he a d mi nistere d ra di oacti vit y  e xcrete d at eac h ti me i nter val a n d t he t otal 
perce nt of d ose rec o vere d i n v o mit us . 
Perce nt rec o ver y  of t otal ra di oacti vit y i n uri ne, feces a n d v o mit us f or C o h ort 1 o nl y , will be 
deter mi ne d base d o n t ot al a d mi nistere d d ose i n C o h ort 1 . Resi d ual ra di oacti vit y  i n t he oral 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
d osi n g c o ntai ner will be re q uire d t o be assesse d i n C o h ort 1 a n d d oc u me nte d i n t he st u d y 
C R F.
I n di vi d ual partici pa nt a n d me dia n data pr ofiles f or t otal ra di oacti vit y will be gra p hicall y 
p rese nte d f or t he c u m ulati ve rec o ver y of ra di oacti vit y i n uri ne, feces a n d t heir c o m bi nati o n
o ver ti me i n C o h ort 1 o nl y . V o mit us , if a n y, will be c ollecte d i n f ull d uri n g t he 
h o urs 
after oral d osi n g i n C o h ort 1 a n d will be re q uire d t o be pr os pecti vel y teste d f or rec o vere d 
ra di oacti vit y. F or e mesis t hat occ urs after 
 h o urs u p t o 
h o urs p ost d ose, sa m ples will be 
c ollecte d i n f ull a n d st ore d f or p ote ntial refle x testi n g f or rec o vere d ra di oacti vit y . These 
parti ci pa nts will n ot necessaril y  be e xcl u de d fr o m a nalys is. T he t otal rec o ver y of 
ra di oacti vit y i n uri ne, feces (a n d v o mit us , if a ny) a n d t heir c o m bi nati o n will be liste d a n d 
s u m marize d f or C o h ort 1 o nl y . 
9. 3. 1. 2.
Met a b olic Pr ofili n g a n d Met a b olite I de ntific ati o n
Plas ma, uri ne a n d fecal sa m ples c ollecte d i n C o h ort 1 will be a nal yz e d f or meta b olites of 
[1 4C] P F - 0 7 2 2 0 0 6 0. Maj or meta b olites of P F-0 7 2 2 0 0 6 0 i n plas ma, uri ne a n d feces ma y be 
i de ntifie d if p ossi ble. C o ntri b uti o ns of pare nt a n d eac h maj or meta b olite t o t otal radi oacti vit y  
rec o vere d i n uri ne a n d feces a n d t o circ ulati n g ra di oacti vit y i n plas ma will be q ua ntifie d if 
p ossi ble. Res ults of t he meta b olic pr ofili n g a nal ysis will be detaile d i n a se parate re p ort a n d 
will be s u m marize d wit hi n t he C S R. 
9. 3. 2. Sec o n d ar y P h ar m ac o ki netic E n d p oi nts
9. 3. 2. 1. A bs ol ute Or al Bi o a v ail a bilit y
A bs ol ute oral bi oa vaila bilit y  ( F) will be esti mate d as t he rati o of ge o metric mea n of d ose-
n or malize d A U C i nf f or oral u nla bele d a n d I V la bele d P F-0 7 2 2 0 0 6 0 (fr o m C o h ort 2 o nl y ) as 
per t he f oll o wi n g e q uati o n:
F = [ P F -0 7 2 2 0 0 6 0 _ A U C p o/[1 4C]- P F -0 7 2 2 0 0 6 0 _ A U C i v] *[[1 4C]-
P F -0 7 2 2 0 0 6 0 _ D ose i v/ P F-0 7 2 2 0 0 6 0 _ D ose p o]
Ge o metric Mea n Rati o a n d 9 0 % c o nfi de nce i nter val: Nat ural l o g tra nsf or me d A U C i nf( d n) (if 
data per mit) a n d A U C last( d n) fr o m C o h ort 2 will be a nal yz e d usi n g a mi xe d effect m o del wit h 
treat me nt as a fi xe d effect a n d partici pa nt varia ble as a ra n d o m effect. Esti mates of t he 
a dj uste d (least s q uares) mea n differe nces ( Test/ Refere nce) a n d t he c orres p o n di n g 
9 0 % c o nfi de nce i nter val i n l o g -scale will be o btai ne d fr o m t he m o del. T he a dj uste d mea n 
differe nces a n d 9 0 % c o nfi de nce i nter vals f or t he differe nces will be e x p o ne ntiate d t o pr o vi de 
esti mates of t he rati o of a dj uste d ge o metric mea n ( Test/ Refere nce) a n d 9 0 % c o nfi de nce 
i nter val f or t he rati o. I V [1 4C] P F - 0 7 2 2 0 0 6 0 will be c o nsi dere d t he Refere nce f or m ulati o n a n d 
u nla bele d oral P F -0 7 2 2 0 0 6 0 will be c o nsi dere d t he Test f or m ulati o n. 
9. 3. 2. 2. Fr acti o n A bs or be d
Fracti o n of d ose a bs or be d ( F a) will be esti mate d as t he rati o of t otal ra di oacti vit y ( d ose 
n or malize d) e xcrete d i nt o t he uri ne (fr o m ti me 0 t o t he ti me of last meas ura ble c o nce ntrati o n) 
 
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 2
f oll o wi n g oral a n d I V a d mi nistrati o n of [1 4C] P F - 0 7 2 2 0 0 6 0 micr otracer d ose s i n C o h ort 1 a n d 
2, res pecti vely : 
F a = [ % T otal 1 4C _ Uri ne _ P O/ % T otal
1 4C _ Uri ne _I V ]
Ge o metric Mea n Rati o : T he rati o ( Test/ Refere nce) of t he ge o metric mea ns of % T otal 1 4C i n 
Uri ne will be esti mate d. T otal 1 4C _ Uri ne _I V is t he Refere nce a n d T otal 1 4C _ Uri ne _ P O is t he 
Test.
A distri b uti o n -free met h o d ( n o n para metric met h o d, H o d ges-Le h ma n n p oi nt esti mate ) ma y be 
c o n d ucte d if e xtre me val ues are e nc o u ntere d i n t he P K para meters . 
C u m ulati ve uri ne 1 4C a m o u nts , perce nt 1 4C d ose as well as F a (calc ulate d usi n g uri ne 1 4C
data, as descri be d a b o ve) will be liste d b y  treat me nt (Oral i n C o h ort 1 a n d I V i n C o h ort 2 ) 
a n d s u m marize d usi n g descri pti ve statistics. I n di vi d ual a n d s u m mar y  pr ofiles of uri ne 1 4C 
will be gra p hicall y prese nte d. 
I n m ost circ u msta nces, Fa esti mati o n base d o n t he uri ne met h o d pr o vi des relia ble F a
esti mates. T otal ra di oacti vit y  f oll o wi n g oral a nd I V a d mi nistrati o n will be ge nerate d fr o m 
differe nt pe o ple i n se parate c o h orts, w here p h ys i ol o gical varia bilit y m a y lea d t o a less r o b ust 
esti mati o n of F a. Differe nt F a calc ulati o n met h o ds ha ve bee n c o m pare d i n detail a n d 
alter nati ve F a calc ulati o n met h o d s f or t his st u d y m a y  be i n vesti gate d as nee de d base d o n 
e mer gi n g dat a. 3
9. 3. 2. 3. 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.
A E s, E C Gs, B P , p ulse rate , a n d safet y la b orat or y data will be re vie we d a n d s u m marize d o n 
a n o n g oi n g basis d uri n g t he st u d y  t o e val uate t he safety of partici pa nt s. A ny cli nical 
la b orat or y, E C G, B P, a n d p ulse rate a b n or malities of p ote ntial cli ni cal c o ncer n will be 
descri be d. Safet y data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d 
descri pti vel y, w here a p pr o priate.
Me dical hist or y  a n d p h ysical e xa mi nati o n a n d ne ur ol o gical e xa mi nati o n i nf or mati o n, as 
a p plica ble, c ollecte d d uri n g t he c o urse of t he st u d y, will be c o nsi dere d s o urce data a n d will 
n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. H o we ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 3. Terti ar y P h ar m ac o ki netic E n d p oi nts
9. 3. 3. 1. Deri v ati o n of P h ar m ac o ki netic P ar a meters
F or C o h ort 1 , f oll o wi n g a si n gle oral a d mi nistrati o n of a micr otracer d ose of 
[1 4C] P F - 0 7 2 2 0 0 6 0, oral P K para meters f or t otal [1 4C] ra di oacti vit y  will be deri ve d fr o m t he 
c o nce ntrati o n e q ui vale nt -ti me pr ofiles, w here a p pr o priate. A d diti o nall y P K para meters f or 
P F - 07 2 2 0 0 6 0 will be c o m p ute d base d o n L C/ M S/ M S a nal y sis of plas ma sa m ples.
F or C o h ort 2 , f oll o wi n g a si n gle oral d ose of P F- 0 7 2 2 0 0 6 0, P K para meters f or P F- 0 7 2 2 0 0 6 0
will be c o m p ute d base d o n L C/ M S/ M S a nal y sis of plas ma sa m ples.
F or C o h ort 2 , f oll o wi n g a si n gle I V micr otracer d ose of [ 1 4C] P F - 0 7 2 2 0 0 6 0 at 2 h o urs p ost 
oral d ose, I V p las ma P K para meters of [1 4C] P F - 0 7 2 2 0 0 6 0 will be deri ve d fr o m plas ma 
ra di oacti vit y c o nce ntrati o n e q ui vale nt-ti me pr ofiles f oll o wi n g c hr o mat o gra p hic se parati o n of 
[1 4C] P F - 0 7 2 2 0 0 6 0 (ie. H P LC- A M S a nal ys is).
T he f oll o wi n g p las ma P K para meters will be deri ve d (a s data per mits) fr o m t he 
c o nce ntrati o n -ti me data usi n g sta n dar d n o nc o m part me ntal met h o ds as o utli ne d i n Ta ble 3 f or
t he a nalyt es a n d a nal ys is met h o ds liste d i n Secti o n 3 . Act ual P K sa m pli n g ti mes will be use d 
i n t he deri vati o n of P K para meters. I n t he case t hat act ual P K sa m pli n g ti mes are n ot 
a vaila ble, n o mi nal P K sa m pli n g ti me will be use d i n t he deri vati o n of P K para meters. Act ual 
a d mi nistere d [ 1 4C] d oses will be use d f or t he t otal [ 1 4C] a n d [ 1 4C] P F - 0 7 2 2 0 0 6 0 P K para meter 
calc ulati o ns.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T a ble 3 .
Pl as m a P K P ar a meters Defi niti o ns
P a r a m eter
Defi niti o n
M e t h o d of Deter mi n ati o n
A U C lasta
Area u n der t he plas ma 
c o nce ntrati o n-ti me pr ofile fr o m 
ti me 0 t o 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 r ule
A U C last( d n)
D ose n or malize d A U C last i n 
C o h ort 2 o nl y
A U C last/ D ose
A U C i nfa
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, 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
A U C i nf( d n)a
D ose n or malize d 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, i n C o h ort 2 o nl y
A U C i nf/ D ose
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
C ma x ( d n)
D ose n or malize d ma xi m u m 
plas ma c o nce ntrati o n, i n C o h ort 2 
o nl y
C ma x / D ose
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 a
T er m i nal eli mi nati o n half-life
L o g e( 2)/ kel
C L a (I V)
C L: s yste mic cleara nce
D ose/ A U C i nf
V ssa (I V)
V ss: Stea d y state v ol u me of 
distri b uti o n f oll o wi n g I V i nf usi o n
C L × [ M R T -(i nf usi o n ti me/ 2)]
w here M R T is t he Mea n Resi de nce Ti me a n d is 
calc ulate d as A U M C i nf/ A U Ci nf
A U M C i nf is t he area u n der t he first m o me nt c ur ve fr o m 0 
ti me t o i nfi nit y. 
C L/ F a ( oral)
A p pare nt cleara nce f oll o wi n g 
oral a d mi nistrati o n
D ose/ A U C i nf
Vz/ F a ( oral)
A p pare nt v ol u me of distr u b uti o n
f oll o wi n g oral a d mi nistrati o n 
D ose /( A U C i nf* k el)
F
A bs ol ute oral bi oa vaila bilit y
[ A U C p o/1 4C A U Ci v] *[ [1 4C]- P F -
0 7 2 2 0 0 6 0 _ D osei v/ P F -0 7 2 2 0 0 6 0 _ D ose p o]
w here,
A U C p o is P F -0 7 2 2 0 0 6 0 area-u n der -t he-plas ma 
c o nce ntrati o n c ur ve f oll o wi n g oral a d mi nistrati o n of 
u nla belle d P F -0 7 2 2 0 0 6 0
P F -0 7 2 2 0 0 6 0 _ D ose p o: Oral d ose of u nla belle d 
P F -0 7 2 2 0 0 6 0
1 4C A U Ci v is P F -0 7 2 2 0 0 6 0 area-u n der -t he-plas ma 
c o nce ntrati o n c ur ve f oll o wi n g I V a d mi nistrati o n of 
[1 4C] P F -0 7 2 2 0 0 6 0
[1 4C]- P F -0 7 2 2 0 0 6 0 D osei v: I V d ose of [1 4C]-
P F -0 7 2 2 0 0 6 0
A U C i nf will be use d u nless data d o n ot all o w  esti mati o n 
of A U C i nf, i n w hic h case, A U Clast will be use d
a.
If data per mits.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 he f oll o wi n g uri ne P K para meters will be calc ulate d usi n g t he o utlie d met h o ds i n Ta ble 4 . 
T a ble 4
Uri ne P K P ar a meters Defi niti o ns
P a r a m eter
Defi niti o n
M e t h o d of Deter mi n ati o n
T otal 1 4C _ Uri ne _ P O
T otal c u m ulati ve ra di oacti vit y e xcrete d 
i nt o uri ne fr o m ti me 0 t o t he ti me of last 
meas ura ble c o nce ntrati o n f oll o w i n g oral 
a d mi nistrati o n of [ 1 4C] P F -0 7 2 2 0 0 6 0
(C o h ort 1 o nl y) 
Directl y fr o m o bser ve d [ 1 4C] data
T otal 1 4C _ Uri ne _I V
T otal c u m ulati ve ra di oacti vit y e xcrete d 
i nt o uri ne fr o m ti me 0 t o t he ti me of last 
meas ura ble c o nce ntrati o n f oll o w i n g 
i ntra ve n o usl y a d mi nistere d 
[1 4C] P F -0 7 2 2 0 0 6 0 micr otracer d ose 
(C o h ort 2 o nl y)
Directl y fr o m o bser ve d [ 1 4C] data
% 
1 4C _ Uri ne _ P O
% of ra di oacti vit y i n t he uri ne f oll o wi n g 
oral a d mi nistrati o n e x presse d as a perce nt 
of t he ra di oacti ve d ose a d mi nistere d 
(C o h ort 1 o nl y)
( T otal 1 4C _ Uri ne _ P O/[ 1 4C] D ose p o) 
* 1 0 0 
w here,
[1 4C] D ose p o is orall y a d mi nistere d 
d ose of [ 1 4C ]P F -0 7 2 2 0 0 6 0
% 
1 4C _ Uri ne _I V  
% of ra di oacti vit y i n t he uri ne f oll o wi n g 
I V a d mi nistrati o n e x presse d as a perce nt of 
t he ra di oacti ve d ose a d mi nistere d 
(C o h ort 2 o nl y)
( T otal 1 4C _ Uri ne _I V/[ 1 4C] D ose i v) 
* 1 0 0 
w here, 
[1 4C] D ose i v is [1 4C] i ntra ve n o usl y 
a d mi nistere d d ose of [ 1 4C] P F -
0 7 2 2 0 0 6 0
F a
Fracti o n A bs or be d
[ T otal 1 4C _ Uri ne _ P O/ T otal 
1 4C _ Uri ne _I V] *[ 1 4C d osei v/ 1 4C d ose p o]
Ae ( P F -0 7 2 2 0 0 6 0
P O i n C o h ort 1)
A m o u nt of u nc ha n ge d dr u g e xcrete d i n 
uri ne
S u m of [ P F -0 7 2 2 0 0 6 0 uri ne 
c o nce ntrati o n * sa m ple v ol u me] f or 
eac h c ollecti o n i nter val
Ae % ( P F -0 7 2 2 0 0 6 0
P O i n C o h ort 1)
Perce nt of d ose rec o vere d u nc ha n ge d i n 
uri ne
Ae/ D ose * 1 0 0
C Lr ( P F -0 7 2 2 0 0 6 0
P O i n C o h ort 1)
Re nal cleara nce ( oral)
Aet/ A U Ct w here Aet is t he a m o u nt of 
u nc ha n ge d dr u g e xcrete d i n uri ne fr o m 
0 ti me u ntil ti me t f oll o wi n g oral d ose 
of P F -0 7 2 2 0 0 6 0
9. 3. 3. 2. T aste Assess me nt
T he data use d i n t he a nal y sis will be tra nscri be d a n d rescale d t o a sc ore fr o m 0 t o 1 0 0 fr o m
t he ra w meas ure me nts o n t he q uesti o n naire. T he se ns or y attri b utes fr o m t he taste 
q uesti o n naires ( A p pe n di x 9 ) will be liste d a n d descri pti vel y  s u m marize d b y q uesti o n acr oss 
p artici pa nts. Ra dar pl ots f or eac h of t he 4 ti me p oi nts , s u m marizi n g all attri b utes will be 
ge nerate d. B o x pl ots of eac h attri b ute will be pl otte d a gai nst t he ti me p oi nts.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 4. Ot her A n al yses 
N ot a p plica ble t o t his st u d y .
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 p pr o xi matel y  6 healt h y a d ult male partici pa nts will be e nr olle d i n eac h of t he 2 c o h orts
base d o n t he i n d ustr y  sta n dar d sa m ple size f or mass bala nce a n d ra di ola bele d micr otracer 
st u dies. T his sa m ple size was n ot c h ose n base d o n a n y e m pirical data or h yp ot hesis testi n g 
criteria. 
 

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

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nt s a gai nst a n y i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. 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 ntative 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 oc iate d 
wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt ’s 
pers o nal data. 
T he partici pa nt m ust be i nf or me d t hat t heir pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priat e 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 vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt is f ull y i nf or me d a b o ut t heir
ri g ht t o access a n d c orrect t heir pers o nal data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of 
t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C D.
Partici pa 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 are rescree ne d are re q uire d t o si g n a ne w I C D.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 9
1 0. 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 or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt -s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nt s w h o partici pate d i n t he st u d y, li n ki n g eac h 
partici pa nt ’s n u merical c o de t o t heir act ual i de ntit y a n d me dical rec or d I D. I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfide ntialit y  of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he cli nical st u d y agree me nt a n d a p plica ble pri vac y  la ws.
I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are 
sec ure d by t ec h nical a n d or ga nizati o nal sec urit y m eas ures desi g ne d t o pr otect s uc h data 
a gai nst acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access.
T he s p o ns or mai ntai ns S O Ps o n h o w t o res p o n d i n t he e ve nt of u na ut h orize d access, use, or 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 0. 1. 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 nicaltrials . g o v ( Cli nical Trials. g o v), t he E u dra C T/ C TIS , a n d/ or 
w w w. pfizer .c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
w w w.cli nicaltrials . g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer- s p o ns ore d i nter ve nti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a pr o d uct, 
re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. T hese r es ults are 
s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
E u dra C T / C TIS
Pfizer p osts cli nical trial res ults o n E u dra C T / C TIS f or Pfizer-s p o ns ore d i nter ve nti o nal st u dies 
i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y  E U re q uire me nts.
w w w. pfizer .c o m
Pfizer p osts C S R s y n o pses a n d plai n -la n g ua ge st u d y res ults s u m maries o n w w w. pfizer .c o m 
f or Pfizer-s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he c orres p o n di n g st u d y res ults 
are p oste d t o w w w.cli nicaltrials . g o v. C S R s y n o pses will ha ve pers o nall y  i de ntifia ble 
i nf or mati o n a n o ny m ize d.
D oc u me nts wit hi n mar keti n g a p plicati o ns
Pfizer c o m plies wit h a p plica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts i ncl u de d 
i n mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y  d oc u me nts a n d C S Rs 
i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A P s. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt h s 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 nally i de ntifia ble 
i nf or mati o n a n o n y m ize d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal yses. Researc h tea ms m ust i ncl u de a bi 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 y i 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ma na ge me nt a n d 
m iti gati o n strate gies a n d anal yt ical ris k- base d m o nit ori n g), met h o ds, res p o nsi bilities , a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n mai ntai ne d 
a n d utilize d b y t he s p o ns or or desi g nee.
T he s p o ns or or desi g nee is res p o 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 part y 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 p a 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 2
1 0. 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 orized site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; 
t hat t he safety a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 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 
pri or ille gal dr u g, alc o h ol, a n d t o bacc o use, as well as bl o o d d o nati o n wit hi n 6 0 da y s pri or t o 
first d ose of P F-0 7 2 2 0 0 6 0 ma 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), partici 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 s ys te m if a vaila ble). 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T h ere ma y be u n pla n ne d sit uati o ns w here t he s p o ns or ma y re q uest me dical rec or ds (e g, 
s hari n g me dical rec or ds s o t hat t he s p o ns or ca n pr o vi de st u d y-relate d a d vice t o t he 
i n vesti gat or). T he me dical rec or ds s h o ul d be s u b mitte d acc or di n g t o t he pr oce d ure descri be d 
a b o ve.
1 0. 1. 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 nt s a n d st u d y s u p plies ha ve bee n c ollecte d a n d a st u d y-site 
cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he s p o ns or 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 heal t 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 ha ll pr o m ptl y i nf or m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t 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
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.
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 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 xceed 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 pretati 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 Pfizer 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. A ll a ut h ors will ha ve 
access t o t he rele va nt statistical ta bles, fi g ures , a n d re p orts (i n t heir ori gi nal f or mat) re q uire d 
t o de vel o p t he p u blicati 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 C T M S . 
T o facilitate access t o t heir i n vesti gat or a n d t he s p o ns or’s M QI f or st u d y-relate d me dical 
q uesti o ns or pr o ble ms fr o m n o n-st u d y healt hcare pr ofessi o nals, partici pa nts are pr o vi de d 
wit h a n E C C at t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr ot oc ol 
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 n c y p h o ne n u m ber acti ve 2 4 h o urs/ da y, 7 da ys per wee k, a n d ( d) Pfizer C all C e nter 
n u m ber.
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. T he Pfizer Call Ce nter n u m ber is t o be use d w he n t he i n vesti gat or a n d site staff 
are u na vaila ble. T he Pfizer Call Ce nter n u m ber is n ot f or use b y t he partici pa nt directly;  if a 
partici pa nt calls t hat n u m ber directl y , t he y will be directe d bac k t o t he i n vesti gat or site.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 obtai 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 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
Retic ul oc yte c o u nt
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils 
( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
B U N
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
T otal bilir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
F or s us pecte d DI LI:
A S T/ A L T
T bili, al b u mi n, C K, direct a n d 
i n direct bili
G G T, P T/I N R, e osi n o p hils 
( %), al kali ne p h os patase
Aceta mi n o p he n/ paraceta m ol 
He patitis ser ol o g y (e ve n if 
scree ni n g ne gati ve)
F or s us pecte d DI CI/ DI KI:
Creati ni ne ( Screat)
C ystati n C a ( Sc ys)
e G F R ( Screat o nl y a n d 
c o m bi ne d Screat + Sc ys)
e Cr Cl b
L ocal di pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y
c
Uri ne Dr u g S cree ni n g d
Uri ne C oti ni ne
At scree ni n g:

He patitis B s urface 
a nti ge n

He patitis B s urface 
a nti b o d y e

He patitis B c ore 
a nti b o d y

He patitis C a nti b o d y

HI V
a.
C ystati n C ( Sc ys): Scree ni n g or Baseli ne Sc ys is rec o m me n de d t o hel p differe ntiate p ost -baseli ne DI KI 
fr o m DI CI. P ost- baseli ne, Sc ys is meas ure d if a n d o nl y if ser u m creati ni ne i ncrease p ost-baseli ne is 
o bser ve d ( see Secti o n 7. 1. 1 ).
b.
Scree ni n g a n d Baseli ne e G F R or e Cr Cl is meas ure d wit h Screat -base d f or m ula. A ge -s pecific ki d ne y 
f u ncti o n calc ulati o n (see Secti o n 1 0. 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.
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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 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
d.
T he mi ni m u m re q uire me nt f or dr u g scree ni n g i ncl u des c oca ine, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot hers are site - a n d st u d y-s pecific).
e.
H Bs A b will be teste d if H Bs A g a n d / or H Bc A b are p ositi ve. 
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical safety la b orat or y  
meas ure me nts at baseli ne a n d at all ti mes after d ose a d mi nistrati o n ma y  be retai ne d a n d 
st ore d f or t he d urati o n of t he st u d y. U p o n c o m pleti o n of t he st u d y, t hese retai ne d safet y 
sa m ples ma y be use d f or t he assess me nt of e x pl orat or y safety bi o mar kers or u ne x pecte d 
safety fi n di n gs . T hese data will n ot be i ncl u de d i n t he C S R . Sa m ples t o be use d f or t his 
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 fac ilit 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 s i g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or 
uri nal y sis) or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y  
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or. A n y 
a b n or mal test res ul ts 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 ditio 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 u l d be re p orte d re gar dless of 
se q uelae.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 8
E ve nts N O T Meeti n g t he A E Defi niti o n

A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts t hat are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  t he 
i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms 
of t he disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is t he A E.

Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s oci al a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).

A ntici pate d da y -t o-d a y  fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) 
prese nt or detecte d at t he start of t he st u d y  t hat d o n ot w orse n.
1 0. 3. 2. Defi niti o n of a n S A E
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose , meets o ne 
or m ore of t he criteri a liste d bel o w:
a.
Res ults i n de at h
b.
Is life-t hre ate ni n g
T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h 
t he partici pa nt was at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n 
e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere.
c.
Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or 
o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h y sicia n’s 
office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
d.
Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T 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 la b orat or y fi n di n gs 
i n dicati n g a n i nfecti o n i n a partici pa nt e x p ose d t o a Pfizer pr o d uct. T he ter ms 
“s us pecte d tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d s y n o n y m o us. T hese 
cases are c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y 
p har m ac 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 ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d 
d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of 
dr u g de pe n de nc y  or dr u g a b use.
1 0. 3. 3. Rec or di n g / Re p orti n g a n d F oll o w - Up of A Es a n d/ or S A E s D uri n g t he Acti ve 
C ollecti o n Peri o d
A E a n d S A E Rec or di n g / Re p orti n g
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g A Es o n t he C R F a n d f or 
re p orti n g S A Es usi n g t he C T S A E Re p ort F or m t o Pfizer Safet y t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; ( 2) 
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. 
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot 
t he sa me as t he A E pa ge of t he C R F. W he n t he sa me data are c ollecte d, t he f or ms m ust 
be c o m plete d i n a c o nsiste nt ma n ner. A Es s h o ul d be rec or de d usi n g c o ncise me dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m 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 
rep orte d * * *
*
E D P ( wit h or wit h o ut a n ass ociate d S A E): is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort 
F or m a n d E D P S u p ple me ntal F or m. 
* * E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m , w hic h w o ul d als o i ncl u de 
details of a n y S A E t hat mi g ht be ass ociate d w it h t he E D B. 
* * * E n vir o n me nt al or o cc u p ati o n al e x p os ure: A E s or S A Es ass ociate d wit h occ u pati o nal e x p os ure 
are re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m . 

W he n a n A E
or S A E occ urs, it is t he res p o nsi bilit y  of t he i n vesti gat or t o re vie w 
all d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m / A E or S A E C R F pa ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by Pfizer Safet y . I n t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0 . 1.9 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her 
ris k fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n 
a d mi nistrati o n , will be c o nsi dere d a n d i n vesti gate d.

T he i n vesti gat or will als o c o ns ult t he I B a n d/ or p r o d uct inf or mati o n, f or 
mar kete d pr o d ucts, i n t heir assess me nt.

F or eac h A E or S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat 
t he y ha ve re vie we d t he A E or S A E a n d ha v e pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p o ns or. H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he 
s p o ns or.

T he i n vesti gat or ma y  c ha n ge t heiro 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 used w he n deter mi ni n g re g ulat or y  
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or 
re p orti n g p ur p oses, as defi ne d b y t he s p o ns or. I n a d diti o n, if t he i n vesti gat or 
deter mi nes t hat a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or 
m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort 
s uc h a n assess me nt i n t he de dicate d 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.
 

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

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 4
1 0. 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 
da ys after t he last d ose of st u d y i nter ve nti o n, w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safet y ris k of t he st u d y  
i nter ve nti o n(s) pl us a n a d diti o nal 9 0  da ys (a s per mat o ge nesis c ycle):

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 or h o m ose x ual i nterc o urse as t heir preferre d a n d 
us ual lifest y le (a bsti ne nt o n a l o n gter 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 a male c o n d o m w he n e n ga gi n g i n a n y  acti vit y t hat all o ws f or 
passa ge of ejac ulate t o a n ot her pers o n.

T he male partici pa nt s h o ul d be a d vi se d of t he be nefit f or a W O C B P part ner usi n g a 
hi g hl y effecti ve met h o d of c o ntrace pti o n wit h a fail ure rate of < 1 % per ye ar, as 
descri be d i n Secti o n 1 0. 4. 3 .
1 0. 4. 2. W o m a n of C hil d be ari n g P ote nti al 
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea i n a d olesce nts or at hletes) a n d a me nstr ual c ycle ca n n ot 
be c o nfir me d bef ore t he first d ose of st u d y  i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P: 
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y d ue t o a me dical ca use ot her t ha n t he a b o ve 
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
 
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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. In a d diti o n:

A hi 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 ntrac e pti o n or H R T. 

A fe male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o 
use o ne of t he hi g hl y effecti ve n o nestr o ge n h or m o nal c o ntrace pti o n met h o ds 
if s he wis hes t o c o nti n ue her H R T d uri n g t he st u d y. Ot her wise, s he m ust 
disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  
e nr oll me nt.
1 0. 4. 3. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat H a ve L o w User De pe n de nc y 
1.
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
2.
I ntra uteri ne de vice.
3.
I ntra uteri ne h or m o ne-releasi n g sys te m.
4.
Bilateral t u bal occl usi o n.
5.
Vasect o mize d part ner.

Vasect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he W O C B P a n d t he a bse nce of s per m has 
bee n c o nf ir me d. If n ot, a n a d diti o nal hi g hly effecti ve met h o d of c o ntrace pti o n 
s h o ul d be use d. T he s per mat o ge nesis c ycle is a p pr o xi matel y 9 0 da ys.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Hi g hl y Effecti ve Met h o ds T hat A re User D e pe n de nt 
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n:

Oral + b arrier *

I ntra va gi nal + b arrier *

Tra ns der mal + b arrier *
7.
Pr o gest o ge n - o 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 
lifest yle of t he partici pa nt.
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o ns 6 or 7 f or t he st u dy 
i ncl u de a ny of t he f oll o wi n g:

Male or fe male c o n d o m wit h or wit h o ut s per mici de;

Ce r vical ca p, dia p hra g m, or s p o n ge wit h s per mici de;

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m , or s p o n ge 
wit h s per mici de ( d o u ble -barrier met h o ds).
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 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 or ot her peri o d as per l ocal re q uire me nts.

Sa m ples f or ge netic researc h will be la bele d wit h a c o de. T h e 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.
 

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

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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. If o n f urt her eval uati o n 
t he a b n or mal test res ult is re peate d, t he partici pa nt s h o ul d be disc o nti n ue d fr o m t he st u d y a n d 
a de q uate, i m me diate, s u p p orti ve meas ures ta ke n . 
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A LT a n d T b ili f or s us pecte d H y ’s la w 
cases , a d diti onal la b orat or y tests s h o ul d i ncl u de al b u mi n, C K, direct a n d i n direct bilir u bi n, 
G G T, P T/I N R, e osi n o p hils ( %), a n d al kali ne p h os p hatase. C o nsi derati o n s h o ul d als o be 
gi ve n t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or 
furt her testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal ys 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 i tself or as a c of or m ulate d 
pr o d uct i n prescri pti o n or o ver -t he-c o u nter me dicati o ns), recreati o nal dr u g, or s u p ple me nt 
( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact 
wit h a ja u n dice d pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d 
p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d. F urt her testi n g f or ac ute 
he patitis A, B, C, D, a n d E i nfecti o n , t otal bile aci ds, li ver i ma gi n g (e g, biliar y tract), a n d 
c ollecti o n of ser u m sa m ples f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct 
le vels ma y  be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T b ili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( Hy’ 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 de d t o calc ulate 2 0 2 1 C K D- E PI  e G F R b y Screat o nly- base d e q uati o n (see Ta b le 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) 4
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
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 p pr o priate 
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 nite d States Nati o nal Ki d ne y  F o u n dati o n O nli ne Calc ulat ors. 

A d ults ( 1 8 y ears a n d a b o ve) - 2 0 2 1 C K D -E PI  Creati ni ne O nli ne Calc ulat or (e G F R): 
htt ps:// w w w. ki d ne y . or g/ pr ofessi o nals/ K D O QI/ gfr _calc ulat or
I n vesti gati o nal sites are res p o nsi ble t o e ns ure t hat t he acc urate a ge-s pecific e q uati o n is 
selecte d a n d t hat t he c orrect u nits f or ser u m creati ni ne ( m g/ d L o nly), ser u m c ystati n C ( m g/ L 
o nl y ), t otal b o dy wei g ht ( k g o nl y), a n d a ge ( y ears). In vesti gat ors are e x pecte d t o (i) re vie w 
a n d c o nfir m c orrect ness of t he ki d ne y  f u ncti o n calc ulati o n res ults a n d (ii) e val uate t he 
calc ulate d val ue wit hi n t he c o nte xt of hist orical i nf or mati o n a vaila ble t o t he m i n t he 
partici pa nt’s me dical rec or d. I n vesti gat ors are res p o nsi ble f or t he cli nical o versi g ht of t he 
partici pa nt eli gi bilit y  pr ocess, ki d ne y f u ncti o n calc ulati o n, a n d d ose selecti o n a n d 
a dj ust me nts per st u d y pr ot oc ol. In vesti gat ors are e nc o ura ge d t o direct q uesti o ns or 
u ncertai nties re gar di n g ki d ne y  f u ncti o n a n d d osi n g t o t he Pfizer Cli nical Tea m a n d Me dical 
M o nit or, if nee de d.
1 0. 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 .
C T C A E 
Ter m ( 2 0 1 7)
Gra de 1  
Gra de 2  
Gra de 3  
Gra de 4  
Gra de 5
A KI
N A
N A
H os pitalizati o n 
i n dicate d
Life -t hreate ni n g 
c o nse q ue nces; 
dial ysis 
i n dicate d
Deat h
A KI: A dis or der c haracterize d b y ac ute l oss of ki d ne y f u ncti o n ( w it hi n 2 wee ks) a n d is tra diti o nall y 
classifie d as pre -re nal (l o w bl o o d fl o w i nt o ki d ne ys), re nal ( ki d ne y da ma ge), or p ost-re nal ca uses ( ureteral or 
bla d der o utfl o w o bstr ucti o n.
Cre ati ni ne 
i ncre ase d
> U L N t o 1. 5 x 
U L N
> 1. 5 t o 3. 0 ×
baseli ne O R 
> 1. 5 t o 3. 0 ×
U L N
> 3. 0 t o 6. 0 ×
baseli ne O R 
> 3. 0 t o 6. 0 ×
U L N
> 6. 0 × U L N
N A
C K D
e G F R ≥6 0 t o 
8 9 
m L/ mi n/ 1. 7 3 m² 
O R                 
e G F R 3 0 t o 5 9 
m L/ mi n/ 1. 7 3 m² 
O R                  
e G F R 1 5 t o 2 9 
m L/ mi n/ 1. 7 3 m² 
O R                
e G F R < 1 5 
m L/ mi n/ 1. 7 3 m² 
O R               
e Cr Cl < 1 5 
Deat h
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
e Cr Cl ≥6 0 t o 
8 0 m L/ mi n 
e Cr Cl 3 0 t o 5 9 
m L/ mi n
e Cr Cl 1 5 t o 2 9 
m L/ mi n
m L/ mi n            
O R            
dial ysis 
i n dicate d
Pr otei n uri a
A D U L T S: 
Pr otei n uria 1 + 
O R                
Pr otei n uria 
> 0. 5 t o < 1. 0 
g/ 2 4 h
A D U L T S: 
Pr otei n uria 2 + 
or 3 +               
O R                
Pr otei n uria 1. 0 
t o < 3. 5 g/ 2 4 h
P E DI A T RI C S:   
U ri ne Pr otei n-
t o-Creati ni ne 
Rati o ( U P C R) 
0. 5 t o 1. 9
A D U L T S: 
Pr otei n uria 4 +               
O R                
Pr otei n uria 
≥3. 5 g/ 2 4 h
P E DI A T RI C S:  
Uri ne Pr otei n -
t o-Creati ni ne 
Rati o ( U P C R) 
> 1. 9
N A
N A
C K D: A dis or der c haracterize d b y gra d ual a n d us uall y per ma ne nt l oss of ki d ne y f u ncti o n res ulti n g i n ki d ne y 
fail ure.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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. 

Atria l 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.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

S ustai ne d su pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) ( “s ustai ne d” = s h ort 
d urati o n wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute) .

Ve ntric ular r h y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h 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 ve rse 
e x perie nce .
T he maj or e ve nts of p ote ntial cli nical c o ncer n liste d a b o ve are rec o m me n de d as “alerts” or n otificati o ns 
fr o m t he c ore E C G la borat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be c o nsi dere d as all-
i ncl usi ve of w hat is t o re p orte d as A Es/ S A Es.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 9. A p pe n di x 9 : Or al S ol uti o n or S us pe nsi o n P al at a bilit y Q uesti o n n aire
1.
Q uesti o n naire s h o ul d be a d mi nistere d t o a d ult p artici pa nt s, prefera bly b y t he cli nicia n or
t he n urse.
2.
Use c ol ore d c o p y of t he Palata bilit y  Q uesti o n naire.
3.
D o n ot alter (re d uce or e nl ar ge) t he ori gi n al size of t he P al at a bilit y Q uesti o n n aire .
4.
Please c ollect t he f oll o wi n g bac k gr o u n d i nf or mati o n:
B ac k gr o u n d I nf or m ati o n
St u d y  #/ St u d y Site
Peri o d a n d Da y
Partici pa nt I D ( Ra n d I D)
Treat me nt
C ollect Date
Q uesti o n naire F ull y  C o m plete d (circle o ne)
Yes/ N o
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 6
Ple ase a ns wer t he f oll o wi n g q uesti o ns a n d pr o vi de a m ar k ( ) o n t he c ol or b ar at 
1 (i m me di atel y), 5, 1 0 a n d 2 0 mi n utes after d osi n g. Ple ase e ns ure p artici p a nt h as access 
t o t hese descri pti o ns w he n c o m pleti n g t he q uesti o n n aire.
Q 1 : Bitter ness – Ple ase tell us a b o ut t he de gree of bitter ness of t he pr o d uct y o u t aste d.
Q 2 : T o n g ue/ m o ut h b ur n – Ple ase tell us a b o ut t he de gree of t o n g ue/ m o ut h b ur n of t he 
pr o d uct y o u t aste d.
Q 3 : T hr o at b ur n – Ple ase tell us a b o ut t he de gree of t hr o at b ur n of t he pr o d uct y o u 
t aste d.
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 7
E x a m ple: H o w t o pr o vi de a m ar k ( ) o n t he c ol or b ar.

G o o d (sc ore = 0)
B a d (sc ore = 1 0 0)
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 8
Wit hi n 1 mi n ute (i m me di atel y) after d osi n g
Pr o vi de a m ar k ( 
) o n t he c ol or b ar.
Bitter ness
T o n g ue/ M o ut h 
B ur n
T hr o at B ur n
N ot Bitter
N o B ur n  
N o B ur n 
E xtre mel y 
Bitter
E xtre me B ur n 
E xtre me B ur n
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 9
5 mi n utes after d osi n g
Pr o vi de a m ar k ( 
) o n t he c ol or b ar.
Bitter ness
T o n g ue/ M o ut h 
B ur n
T hr o at B ur n
N ot Bitter
N o B ur n  
N o B ur n 
E xtre mel y 
Bitter
E xtre me B ur n 
E xtre me B ur n
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 0
1 0 mi n utes after d osi n g
Pr o vi de a m ar k ( 
) o n t he c ol or b ar .
Bitter ness
T o n g ue/ M o ut h 
B ur n
T hr o at B ur n
N ot Bitter
N o B ur n  
N o B ur n 
E xtre mel y 
Bitter
E xtre me B ur n 
E xtre me B ur n
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 1
2 0 mi n utes after d osi n g
Pr o vi de a m ar k ( 
) o n t he c ol or b ar.
Bitter ness
T o n g ue/ M o ut h 
B ur n
T hr o at B ur n
N ot Bitter
N o B ur n  
N o B ur n 
E xtre mel y 
Bitter
E xtre me B ur n 
E xtre me B ur n
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 2
A d diti o n al Fee d b ac k – After c o m pleti n g t he “ 2 0 mi n ute after d osi n g” palata bilit y q uesti o ns ,
please pr o vi de a n y a d diti o nal descri pti ve fee d bac k i n t he b o x bel o w re gar di n g t he taste or 
o d or of t he pr o d uct .
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 3
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 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verit y sta n dar dizati o n)
A bs
a bs ol ute
A D L
acti vit y/ acti vities of dail y li vi n g
A D M E
A bs or pti o n, Distri b uti o n, Meta b olis m a n d E xcreti o n
A E
a d verse e ve nt
Ae %
Perce nt of d ose rec o vere d u nc ha n ge d i n uri ne
Ae( ∞)
C u m ulati ve a m o u nt of u nc ha n ge d dr u g e xcrete d i n uri ne fr o m ti me 0 
e xtra p olate d t o i nfi nite ti me
A KI
ac ute ki d ne y  i nj ur y
A L T
ala ni ne a mi n otra nsferase
A M S
accelerat or mass s pectr o metr y
A PI
acti ve p har mace utical i n gre die nt
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
A U C 2 4
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m ti me 0 t o 2 4 
h o urs p ost d ose
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 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 pr ofile fr o m ti me 0 t o 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 U C ta u
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve o ver t he d osi n g 
i nter val
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
B B S
Bi os peci me n Ba n ki n g S yste m
B C S
Bi o p har mace utics Classificati o n S y ste m
BI D
t wice daily
B L Q
bel o w t he li mit of q ua ntificati o n
B MI
b o d y  mass i n de x
B P
bl o o d press ure
b p m
beats per mi n ute
B U N
bl o o d urea nitr o ge n
C D K
c ycli n-de pe n de nt ki nase
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 CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 4
A b bre vi ati o n
Ter m
C L
s yste mic cleara nce
C L / F
a p pare nt cleara nce
C L R
re nal cleara nce
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C ma x ( d n)
d ose n or malize d C ma x
C M C
C he mistr y , Ma n ufact uri n g a n d C o ntr ols
C mi n
t he mi ni m u m bl o o d plas ma c o nce ntrati o n reac he d b y a dr u g d uri n g a 
d osi n g i nter val
C O 2
car b o n di o xi de ( bicar b o nate)
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 T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C TI S
Cli nical Trial I nf or mati o n S y ste m
C T M S
Cli nical Trial Ma na ge me nt S y ste m
C V
coefficie nt of variati o n
C Y P
c yt oc hr o me P 4 5 0
D C T
data c ollecti o n t o ol
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 L T
d ose -li miti n g t o xicit y
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
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 S A E
electr o nic seri o us a d verse e ve nt
E T
en d ocri ne t hera p y
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 n ical Trials 
(E ur o pea n Cli nical Trials Data base )
F
oral bi oa vaila bilit y
F a
fracti o n a bs or be d
F D A
F o o d a n d Dr u g A d mi nistrati o n
 

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 5
A b bre vi ati o n
Ter m
F S H
f ollicle-sti m ulati n g h or m o ne
F U
f oll o w-u p
f u
fracti o n u n b o u n d
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
G M P
G o o d Ma n ufact ure
Practice
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C V A b
he patitis C a nti b o d y
Her 2 -
h u ma n e pi der mal gr o wt h fact or rece pt or 2 ne gati ve
h E R G
H u ma n et her -à-g o -g o relate d ge ne
HI V
h u ma n i m m u n o deficie nc y vir us
H P L C
hi g h perf or ma nce li q ui d c hr o mat o gra p h y
H R
heart rate
H R +
h or m o ne rece pt or p ositi ve
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 B S
irrita ble b o wel sy n dr o me
I C 5 0
5 0 % i n hi biti ve c o nce ntrati o n
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use
I C R P
I nter nati o nal C o m missi o n o n Ra di ol o gical Pr otecti o n
I D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal Ne w Dr u g 
I N R
i nter nati o nal n or malize d rati o
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I RB
I nstit uti o nal Re vie w B oar d
I V
intra ve n o us(l y)
K
Pr o p orti o nalit y  c o nsta nt f or Sc h wartz E q uati o ns ( ki d ne y f u ncti o n)
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
K 2E D T A
di p otassi u m et h y le ne dia mi netetraacetic aci d
L B B B
left b u n dle bra nc h bl oc k
L C M S
li q ui d c hr o mat o gra p hy m ass s pectr o metr y
L C/ M S/ M S
Li q ui d c hr o mat o gra p h y t a n de m mass s pectr o metr y
L F T
li ver f u ncti o n test
L L N
l o wer li mit of n or mal
L S C
Li q ui d Sci ntillati o n C o u nti n g 
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 6
A b bre vi ati o n
Ter m
m B C
Metastatic breast ca ncer
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
M R E C
Me dical Researc h Et hics C o m mittee
M T D
m a xi m u m tolerate d d ose
N A
n ot a p plica ble
N L
t he Net herla n ds 
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 B M C
peri p heral bl o o d m o n o n uclear cell
P D
p har mac o d y n a mic(s)
P G x 
p har mac o ge n o mic(s)
P K
p har mac o ki netic(s)
P O
oral(l y)
P R
p ulse rate
P S S A
Pfizer ’s Seri o us A d verse E ve nt S u b missi o n Assista nt
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R D E
Rec o m me n de d d ose f or e x pa nsi o n
R FI
re q uest f or inf or mati o n
R N A
ri b o n ucleic aci d
S A E
seri o us a d verse e ve nt
S AI
Site A d mi nistrati o n I nstr ucti o ns
S A P
Statistical A nal y sis Pla n
S C
s u bc uta ne o us
S C L
s u p pl y c hai n lea d
Screat
ser u m creati ni ne 
Sc y s
ser u m c ystati n C
S o A
sc he d ule of acti vities
S O P
sta n dar d o perati n g pr oce d ure
S P F
su n pr otecti o n fact or
S R S D
Si n gle Refere nce Safet y D oc u me nt
 
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 7
A b bre vi ati o n
Ter m
S T -T
S T se g me nt a n d T wa ve
S U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n
t½
Ter mi nal p hase eli mi nati o n half -life
T A
Tec h nical A gree me nt 
T B
t u berc ul osis 
T bili
t otal bilir u bi n
T E A E
treat me nt-e mer ge nt a d verse e ve nt
T H C
tetra hy dr oca n na bi n ol
T K 6
t h ymi di ne ki nase cells
T ma x
ti me f or Cma x
U A C R
uri ne al b u mi n/creati ni ne rati o
U G T
uri di ne di p h os p ha te-gl uc ur o n os y ltra nsferase
U L N
u p per li mit of n or mal
U P C R
uri ne pr otei n/creati ni ne rati o
U S
U nite d States
U TI
uri nar y  tract i nfecti on
V ss
stea d y state v ol u me of distri b uti o n
V z/ F
a p pare nt v ol u me of distr ib uti o n
W B A
w h ole b o d y  a ut ora di o gra p h y
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
 
C CI
C CI

P F -0 7 2 2 0 0 6 0
Pr ot oc ol C 4 3 9 1 0 1 0
Pr ot oc ol A me n d me nt 1 , 0 6 Dece m ber 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 8
1 1. R E F E R E N C E S
1. 
I C H T o pic M 3 ( R 2). N o n- cli nical safet y st u dies f or t he c o n d uct of h u ma n cli nical trials 
a n d mar keti n g a ut h orizati o n f or p har mace uticals. I nter nati o nal C o nfere nce o n 
Har m o nisati o n of Tec h nical Re q uire me nts f or Re gistrati o n of P har mace uticals f or 
H u ma n Use ( 2 0 0 9).
2. 
F D A G ui da nce “ Wai ver of I n Vi v o Bi oa vaila bilit y  a n d Bi oe q ui vale nce St u dies f or 
I m me diate-Release S oli d Oral D osa g e F or ms Base d o n a Bi o p har mace utics 
Classificati o n S y ste m”. Dece m ber 2 0 1 7. 
3.
M o deli n g S u m mar y  t o S u p p ort Fa Rec o m me n dati o ns, V 2. 
4.
I n ker L A, E nea nya  N D, C ores h J, et al. Ne w Creati ni ne- a n d C ystati n C-Base d 
E q uati o ns t o Esti mate G F R wit h o ut Race. N E n gl J Me d. 2 0 2 1; 3 8 5( 1 9): 1 7 3 7- 4 9 .