A Phase 1, Open-Label, 2-Period, Fixed Sequence Study to Estimate the Effect of Itraconazole on the Pharmacokinetics of PF-07817883 in Healthy Adults
Phase: PHASE1
Conditions: Healthy
Sponsor: Pfizer

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1
A P H A S E 1, O P E N -L A B E L, 2- P E RI O D, FI X E D S E Q U E N C E S T U D Y T O 
E S TI M A T E T H E E F F E C T O F I T R A C O N A Z O L E O N T H E P H A R M A C O KI N E TI C S 
O F P F -0 7 8 1 7 8 8 3 I N H E A L T H Y A D U L T S
St u d y I nter ve nti o n N u m ber :
P F -0 7 8 1 7 8 8 3
St u d y I nter ve nti o n N a me:
N A
U S I N D N u m ber:
1 6 2 6 4 4
E u dr a C T N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 0 9 1 0 0 8
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A St u d y  t o Lear n A b o ut H o w Itrac o naz ole Affects t he Bl o o d Le vel of St u d y  
I nter ve nti o n P F -0 7 8 1 7 8 8 3 i n Healt h y  A d ults
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nt s, yo u a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or 
use it f or u na ut h orize d p ur p oses. I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 1
1 9 A pril 2 0 2 3
Ori gi nal pr ot oc ol
1 7 M arc h 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 (1 9 A pril 2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt: 
T o i ncl u de dr u g -pr o d uct acce pt a bilit y assess me nt f oll o wi n g t he d ose of P F -0 7 8 1 7 8 8 3
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
S u bst a nti al M o dific ati o n(s)
A d de d t he acti vit y of 
“ dr u g-pr o d uct
acce pta bilit y”.
U p date d t o reflect t he 
c ha n ge i n sc he d ule of 
acti vities
Secti o n 1. 3 Sc he d ule of 
Acti vities a n d Secti o n 1 0. 9 
A p pe n di x 9 Dr u g Pr o d uct 
Acce pta bilit y  Q uesti o n naire.
A d de d 1 e x pl orat or y  
e n d p oi nt f or t he e val uati o n 
of acce pta bilit y  of 
P F - 0 7 8 1 7 8 8 3 i n healt hy 
partici pa nts.
U p date d t o reflect t he 
a d diti o n of a n e x pl orat or y 
e n d p oi nt
Secti o n 3 O bjecti ves a n d 
E n d p oi nts
A d de d t he dr u g- pr o d uct 
acce pta bilit y q uesti o n naire 
t o t he st u d y desi g n of 
Peri o d 1.
T o assess acce pta bilit y  of 
t he f or m ulati o n 
Secti o n 4. 1 O verall Desi g n
N o n -s u bst a nti al M o dific ati o n(s)
C orrecte d t he visit i de ntifier 
i n t he S o A Ta ble 1
C orrecte d err ors
Secti o n 1. 3 Ta ble 1
A d de d “at t he site” i n 
“a d mi nistrati o n of st u d y 
i nter ve nti o n(s) at t he site”
U p date d per c ha n ges i n 
pr ot oc ol te m plate f or 
clarificati o n
Secti o n 6. 1. 1 A d mi nistrati o n
U p date d t he p ote ntial cases 
of ac ute ki d ne y  i nj ur y, an d 
U p date d per c ha n ges i n 
pr ot oc ol te m plate
Secti o n 7. 1. 1 P ote ntial 
Cases of Ac ute Ki d ne y  
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
t he assess me nt of ki d ne y  
f u ncti o n
I nj ur y, Secti o n 1 0. 7. 1 
La b orat or y  Assess me nt of 
C ha n ge i n Ki d ne y  F u ncti o n 
a n d Detecti o n of Ki d ne y 
I nj ur y, a n d Secti o n 1 0. 7. 3 
A d verse E ve nt Gra di n g f or 
Ki d ne y  Safety La b orat or y 
A b n or malities
U p date d t he ti me peri o d f or 
S A E c ollecti o n
U p date d per c ha n ges i n 
pr ot oc ol te m plate
Secti 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 mati o n
Re m o ve d “ D P -0 0 5 8 0 6 or 
D P -0 0 5 8 0 8” fr o m t he 
c urre nt na me of t he st u d y 
i nter ve nti o n
P A C L  date d 0 7 A pr 2 0 2 3
Secti o n 6. 1 St u d y  
I nter ve nti o n(s) 
A d mi nistere d
Re m o ve d “ O nl y if uri ne 
di pstic k is p ositi ve f or 
bl o o d, pr otei n, nitrites, or 
le u k oc yte esterase a n d 
c ult ure o nl y if bacteri uria” 
fr o m f o ot n ote b i n Ta ble 7
P A C L  date d 0 7 A pr 2 0 2 3
Secti o n 1 0. 2 A p pe n di x 2: 
Cli nical L a b orat or y Tests
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4
T A B L E O F C O N T E N T S
LI S T O F T A B L E S .....................................................................................................................9
1. P R O T O C O L  S U M M A R Y................................................................................................... 1 0
1. 1. S y n o psis .................................................................................................................. 1 0
1. 2. Sc he ma .................................................................................................................... 1 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 3
2. 1. St u d y  Rati o nale....................................................................................................... 2 3
2. 2. Bac k gr o u n d ............................................................................................................. 2 3
2. 2. 1. Disease O ver vie w ....................................................................................... 2 3
2. 2. 2. C urre nt Treat me nt O pti o ns......................................................................... 2 3
2. 2. 3. Rati o nale f or De vel o p me nt of P F -0 7 8 1 7 8 8 3.............................................. 2 4
2. 2. 4. N o ncli nical O ver vie w ................................................................................. 2 4
2. 2. 5. Bi o p har mace utics a n d N o ncli nical P har mac o ki netics ................................ 2 4
2. 2. 5. 1. Bi o p har mace utics ...................................................................... 2 4
2. 2. 5. 2. N o ncli nical P har mac o ki netics a n d i n vitr o Meta b olis m ........... 2 4
2. 2. 6. T o xic ol o g y  of P F-0 7 8 1 7 8 8 3....................................................................... 2 5
2. 2. 7. Cli nical O ver vie w ....................................................................................... 2 5
2. 2. 7. 1. S u m mar y  of P F-0 7 8 1 7 8 8 3 P har mac o ki netics i n H u ma ns ........ 2 6
2. 2. 7. 2. Safet y O ver vie w ........................................................................ 2 6
2. 3. Be nefit/ Ris k Assess me nt ......................................................................................... 2 7
2. 3. 1. Ris k Assess me nt ......................................................................................... 2 8
2. 3. 2. Be nefit Assess me nt ..................................................................................... 2 9
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................2 9
3. O BJ E C TI V E S A N D E N D P OI N T S ..................................................................................... 2 9
4. S T U D Y D E SI G N ................................................................................................................. 2 9
4. 1. O verall Desi g n ......................................................................................................... 2 9
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n..................................................................... 3 1
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................3 1
4. 3. J ustificati o n f or D ose ..............................................................................................3 1
4. 4. E n d of St u d y  Defi niti o n .......................................................................................... 3 2
5. S T U D Y P O P U L A T I ON ......................................................................................................3 2
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 1. I ncl usi o n Criteria ..................................................................................................... 3 3
5. 2. E xcl usi o n Criteria .................................................................................................... 3 3
5. 3. L ifest yle C o nsi derati o ns.......................................................................................... 3 5
5. 3. 1. C o ntrace pti o n ..............................................................................................3 5
5. 3. 2. Meals a n d Dietar y  Restricti o ns................................................................... 3 6
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o ................................................................. 3 7
5. 3. 4. Acti vit y ....................................................................................................... 3 7
5. 4. Scree n Fail ures ........................................................................................................ 3 7
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y ................................. 3 7
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................ 3 8
6. 1. 1. A d mi nistrati o n ............................................................................................ 3 9
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ............................................... 3 9
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................ 4 0
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ........................................................................... 4 0
6. 4. Bli n di n g ................................................................................................................... 4 1
6. 5. St u d y  Inter ve nti o n C o m plia nce ............................................................................... 4 1
6. 6. D ose M o dificati o n ................................................................................................... 4 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 ...................... 4 1
6. 8. Treat me nt of O ver d ose ............................................................................................ 4 1
6. 9. Pri or a n d C o nc o mita nt T hera p y .............................................................................. 4 1
6. 9. 1. Resc ue Me dici ne ......................................................................................... 4 2
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 PA R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ........................................................................... 4 2
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n .................................................................... 4 2
7. 1. 1. P ote ntial Cases of Ac ute Ki d ne y  Inj ur y .....................................................4 2
7. 1. 2. E C G C ha n ges ..............................................................................................4 4
7. 1. 3. C O V I D-1 9 ................................ ..................................................................4 4
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................4 4
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................4 5
7. 3. L ost t o F oll o w -U p ................................................................................................... 4 5
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...............................................................4 6
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures ................................................................. 4 6
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 2. Efficac y  Assess me nts..............................................................................................4 7
8. 3. Safet y Assess me nts .................................................................................................4 7
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................ 4 7
8. 3. 2. Vital Si g ns .................................................................................................. 4 8
8. 3. 2. 1. Bl o o d Press ure a n d P ulse Rate .................................................. 4 8
8. 3. 2. 2. Res pirat or y  Rate........................................................................ 4 8
8. 3. 3. Electr ocar di o gra ms ..................................................................................... 4 8
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts.................................................... 4 9
8. 3. 5. C O VI D -1 9 S pecific Assess me nts............................................................... 5 0
8. 3. 6. Pre g na nc y  Testi n g ...................................................................................... 5 0
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 0
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 1
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ............................................... 5 1
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F ................... 5 1
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es .......................................................... 5 2
8. 4. 3. F oll o w -U p of A Es a n d S A Es ...................................................................... 5 2
8. 4. 4. Re g ulat or y  Re p orti n g Re q uire me nts f or S A Es........................................... 5 2
8. 4. 5. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure ..................................................... 5 3
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ...................................................... 5 3
8. 4. 5. 2. E x p os ure D u ri n g Breastfee di n g ................................................ 5 4
8. 4. 5. 3. Occ u pati o nal E x p os ure ............................................................. 5 5
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................5 5
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 .............................................................................. 5 5
8. 4. 8. A d verse E ve nts of S pecial I nterest ............................................................. 5 5
8. 4. 8. 1. Lac k of Efficac y ........................................................................ 5 5
8. 4. 9. Me dical De vice Deficie ncies ......................................................................5 5
8. 4. 1 0. Me dicati o n Err ors ..................................................................................... 5 5
8. 5. P har mac o ki netics .................................................................................................... 5 6
8. 5. 1. Plas ma f or A nal ys is of P F-0 7 8 1 7 8 8 3......................................................... 5 6
8. 5. 2. Uri ne f or A nal ys is of P F-0 7 8 1 7 8 8 3 ........................................................... 5 7
8. 6. Ge netics ................................................................................................................... 5 8
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 6. 1. S pecifie d Ge netics ...................................................................................... 5 8
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics ................................................... 5 8
8. 7. Bi o mar kers .............................................................................................................. 5 8
8. 8. I m m u n o g e nicit y Assess me nts ................................................................................. 5 8
8. 9. Healt h Ec o n o mics ................................................................................................... 5 8
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 5 8
9. 1. Statistical H y p ot heses ............................................................................................. 5 8
9. 2. A nal y sis Sets ........................................................................................................... 5 9
9. 3. Statistical A nal y ses ................................................................................................. 5 9
9. 3. 1. P har mac o ki netic A nal y ses .......................................................................... 5 9
9. 3. 1. 1. Deri vati o n of P har mac o ki netic Para meters ............................... 5 9
9. 3. 2. Statistical Met h o ds f or P K Data ................................................................. 6 1
9. 3. 3. Ot her Safet y A nal yses ................................................................................ 6 1
9. 3. 4. Ot her A nal ys es ............................................................................................ 6 1
9. 4. I nteri m A nal ys es ..................................................................................................... 6 1
9. 5. S a m ple Size Deter mi nati o n..................................................................................... 6 2
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S .......................................................................................................... 6 3
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns............... 6 3
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns .................................................... 6 3
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P ......................................................................... 6 3
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................ 6 4
1 0. 1. 3. Data Pr otecti o n ......................................................................................... 6 5
1 0. 1 . 4. C o m mittees Str uct ure ............................................................................... 6 5
1 0. 1. 4. 1. Data M o nit ori n g C o m mittee ................................................... 6 5
1 0. 1. 5. Disse mi nati o n of Cli nical St u d y  Data ...................................................... 6 5
1 0. 1. 6. Data Q ualit y Ass ura nce ............................................................................ 6 6
1 0. 1. 7. S o urce D oc u me nts .................................................................................... 6 8
1 0. 1. 8. Use of Me dical Rec or ds ............................................................................6 8
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................6 9
1 0. 1. 1 0. P u blicati o n P olic y ...................................................................................6 9
1 0. 1. 1 1. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................7 0
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests................................................................. 7 1
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 ..................................................................... 7 2
1 0. 3. 1. Defi niti o n of A E ....................................................................................... 7 2
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................ 7 3
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............................................................................ 7 4
1 0. 3. 4. Re p orti n g of S A Es .................................................................................... 7 8
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................ 7 9
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................... 7 9
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria ................................. 7 9
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................ 8 0
1 0. 4. 4. C o ntrace pti o n Met h o ds ............................................................................. 8 1
1 0. 5. A p pe n di x 5: Ge netics ............................................................................................ 8 3
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 ....... 8 4
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 ............................................ 8 6
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 .............................................................................. 8 6
1 0. 7. 2. A g e-S pecific Ki d ne y  F u ncti o n Calc ulati o n Rec o m me n dati o ns............... 8 6
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........................................................................................... 8 6
1 0. 7. 3. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ................................................................................................... 8 6
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 ................................... 8 8
1 0. 9. A p pe n di x 9: Dr u g Pr o d uct Acce pta bilit y  Q uesti o n naire ...................................... 9 0
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns ............................................................................... 9 2
1 1. R E F E R E N C E S ..................................................................................................................9 7
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
LI S T O F T A B L E S
Ta ble 1.
Peri o d 1 ( P F- 0 7 8 1 7 8 8 3 Al o ne): Scree ni n g T hr o u g h Peri o d 1 Da y  5.......1 8
Ta ble 2.
Peri o d 1 ( P F- 0 7 8 1 7 8 8 3 Al o ne): Detaile d Sa m pli n g Sc he d ule ................. 2 0
Ta ble 3.
Peri o d 2 ( P F- 0 7 8 1 7 8 8 3 Wit h I trac o naz ole): Da y 1 T hr o u g h Da y 8 ........ 2 1
Ta ble 4.
Peri o d 2 ( P F- 0 7 8 1 7 8 8 3 Wit h I trac o naz ole): Detaile d Sa m pli n g 
Sc he d ule .................................................................................................... 2 2
Ta ble 5.
Plas ma P F -0 7 8 1 7 8 8 3 P K Para meter Defi niti o ns...................................... 6 0
Ta ble 6.
Uri ne P F -0 7 8 1 7 8 8 3 P K para meter defi niti o ns ......................................... 6 0
Ta ble 7.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts............................................. 7 1
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: A P hase 1, O pe n -La bel, 2- Peri o d, Fi xe d Se q ue nce St u d y  t o Esti mate t he 
Effect of Itrac o naz ole o n t he P har mac o ki netics of P F- 0 7 8 1 7 8 8 3 i n Healt h y A d ults
Brief Title: A St u d y  t o Lear n A b o ut H o w Itrac o naz ole Affects t he Bl o o d Le vel of St u d y 
I nter ve nti o n P F -0 7 8 1 7 8 8 3 i n Healt h y  A d ults
Re g ul at or y A ge nc y I de ntific ati o n N u m ber(s):
U S I N D N u m ber:
1 6 2 6 4 4
E u dr a C T N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 0 9 1 0 0 8
P h ase:
1
R ati o n ale :
P F -0 7 8 1 7 8 8 3 is a p ote nt a n d selecti ve i n hi bit or of t he S A R S -C o V -2 M pr o t hat is c urre ntly 
bei n g de vel o pe d as a n oral treat me nt of C O VI D -1 9.
I n vitr o a n d i n vi v o (i n rats) meta b olite pr ofili n g s u g gests t hat t he pri mar y  meta b olic r o ute
f or P F-0 7 8 1 7 8 8 3 is C Y P -me diate d o xi dati o n. I n vitr o st u dies usi n g h u ma n li ver micr os o mes
i n dicate d meta b olis m of P F -0 7 8 1 7 8 8 3 was pre d o mi na ntl y  me diate d b y C Y P 3 A 4 
.
T he p ur p ose of t his st u d y is t o esti mate t he effect of a str o n g i n hi bit or of C Y P 3 A 4 o n t he P K 
of P F -0 7 8 1 7 8 8 3 i n healt h y  a d ult partici pa nts. Res ults of t his st u d y will pr o vi de g ui da nce f or 
d osi n g rec o m me n dati o ns wit h c o nc o mita nt me dicati o ns t hat ha ve C Y P 3 A i n hi bit or y  
p ote ntial .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 esti mate t he effect of m ulti ple d oses of 
itrac o naz ole 2 0 0 m g Q D o n t he P K of P F - 0 7 8 1 7 8 8 3 
f oll o wi n g a si n gle oral d ose of P F -0 7 8 1 7 8 8 3
3 0 0 m g

P F -0 7 8 1 7 8 8 3 plas ma P K para meters : Cma x a n d A U C i nf (if 
data per mit s, ot her wise A U Clast) wit h itrac o naz ole (test) 
vers us wit h o ut itrac o naz ole (refere nce)
Sec o n d ar y: 
Sec o n d ar y:

T o e val uate t he safet y a n d t olera bilit y of 
P F - 0 7 8 1 7 8 8 3 i n healt h y partici pa nts i n t he a bse nce 
a n d prese nce of m ulti ple d oses of itrac o naz ole

T o c haracterize a d diti o nal P K  para meters of 
P F - 0 7 8 1 7 8 8 3 w he n a d mi nistere d al o ne or wit h 
itrac o naz ole i n healt h y partici pa nts

Assess me nt of T E A Es, cli nical la b orat or y a b n or malities, 
vital si g ns, p h ysical e xa ms, a n d 1 2- lea d E C Gs

P F -0 7 8 1 7 8 8 3 plas ma P K para meters : Tma x , a n d if data 
per mits , t½ , C L/ F , V z/ F, wit h a n d wit h o ut c oa d mi nistrati o n 
of itrac o naz ole
O ver all Desi g n :
T his is a P hase 1, o pe n -la bel, 2-peri o d, fi xe d se q ue nce st u d y  t o esti mate t he effect of 
itrac o naz ole, a str o n g C Y P 3 A 4 i n hi bit or, o n t he plas ma P K of P F -0 7 8 1 7 8 8 3 i n healt h y  
a d ults. T he st u d y will c o nsist of 2 treat me nts: a si n gle oral d ose of P F -0 7 8 1 7 8 8 3 3 0 0 m g 
al o ne a n d a si n gle oral d ose of P F - 0 7 8 1 7 8 8 3 3 0 0 m g i n c o m bi nati o n wit h m ulti ple oral d oses 
of itrac o naz ole 2 0 0 m g Q D . A t otal of a p pr o xi matel y 1 2 healt h y a d ults will be e nr olle d t o 
e ns ure at least 1 0 partici pa nts c o m plete t he st u d y. Partici pa nts w h o disc o nti n ue fr o m t he 
st u d y f or n o n-safet y reas o ns ma y be re place d at t he s p o ns or’s discreti o n i n c olla b orati o n wit h 
t he i n vesti gat or.
Healt h y partici pa nts will be scree ne d t o deter mi ne eli gi bilit y  wit hi n 2 8 da ys pri or t o st u d y 
treat me nt. Me dical hist or y an d res ults of p h y sical e xa mi nati o n, p h ysical meas ure me nts, vital 
si g ns, 1 2-lea d E C Gs, a n d cli nical la b orat or y e val uati o ns will deter mi ne eli gi bilit y. 
Partici pa nts will re p ort t o t he P C R U o n Peri o d 1 Da y  - 1 ( St u d y D a y -1) a n d will be re q uire d 
t o sta y i n t he P C R U f or 1 3 da y s a n d 1 2 ni g hts.
I n Peri o d 1, eac h e nr olle d partici pa nt will recei ve a si n gle oral d ose of P F -0 7 8 1 7 8 8 3 3 0 0 m g 
i n t he m or ni n g of Da y 1. Serial plas ma P K sa m ples will be c ollecte d u p t o 9 6 h o urs a n d uri ne 
will be c ollecte d u p t o 2 4 h o urs after P F -0 7 8 1 7 8 8 3 d ose o n Da y  1. 
Partici pa nts will recei ve itrac o naz ole 2 0 0 m g a d mi nistere d orall y Q D o n Peri o d 2 Da ys 1 -7
( St u d y Da ys 5- 1 1), i ncl usi ve. P artici pa nts will recei ve a si n gle oral d ose of P F - 0 7 8 1 7 8 8 3 
3 0 0 m g i n t he m or ni n g of Peri o d 2 Da y 4 ( St u d y D a y 8). F oll o wi n g t he a d mi nistrati o n of 
P F -0 7 8 1 7 8 8 3 o n Peri o d 2 D a y  4, partici pa nts will u n der g o serial P K sa m pli n g u p t o 9 6 h o urs
a n d uri ne c ollecti o n u p t o 2 4 h o urs. As a res ult, t he was h o ut i nter val bet wee n d osi n g of 
P F -0 7 8 1 7 8 8 3 i n Peri o d 1 a n d Per i o d 2 is 7 da ys. Partici pa nts ma y be c o nfi ne d at t he P C R U 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
d uri n g t he e ntire d urati o n of t he st u d y , a n d t he y will be disc har ge d fr o m t he P C R U o n 
Peri o d 2 Da y 8 ( St u d y D a y 1 2) f oll o wi n g c o m pleti o n of all assess me nts.
A f oll o w -u p ( w hic h ma y be a p h o ne call) will be ma de t o partici pa nts a p pr o xi matel y  2 8 t o 
3 5 da y s fr o m a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n.
N u m ber of P artici p a nts:
A p pr o xi matel y  1 2 partici pa nts will be e nr olle d i n t he st u d y.
N ote: “E nr olle d ” mea ns a partici pa nt ’s, or t heir legall 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 assi g n me nt t o st u d y i nter ve nti o n. A partici pa nt will be c o nsi dere d e nr olle 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. 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.
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 k e 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:
A ge a n d Se x:
1.
Male a n d fe male partici pa nts a ge d 1 8 t o 6 5 ye ars of a ge, i ncl usi ve, at scree ni n g w h o 
are o vertl y healt h y as deter mi ne d by me dical e val uati o n i ncl u di n g me dical hist or y, 
p h y sical e xa mi nati o n, la b orat or y tests, a n d sta n dar d 1 2-lea d E C G. 
Ot her I ncl usi o n Criteri a: 
2.
B MI of 1 7. 5 t o 3 2 k g/ m 2; a n d a t otal b od y  wei g ht > 5 0 k g ( 1 1 0 l b). 
3.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt .
4.
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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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:
Me dic al C o n diti o ns:
1.
A n y  me dical or psyc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/ be ha vi or or la b orat 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 
partici pa nt i na p pr o priate f or t he st u d y.
2.
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, C V , he patic, psyc hiat ric, 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 ym pt o matic, seas o nal aller gies at 
t he ti me of d osi n g) a n d, i n t he j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he 
partici pa nt i na p pr o priate f or e ntr y  i nt o t his st u d y.
3.
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).
4.
P ositi ve test res ult f or S A R S -C o V -2 i nfecti o n at a d missi o n. 
Pri or/ C o nc o mit a nt T her a p y:
5.
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 
wi t hi n 2 8 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 (refer t o Secti o n 6. 9 f or a d diti o nal details).
6.
Partici pa nts w h o ha ve recei ve d a C O VI D- 1 9/fl u vacci ne(s) wit hi n 7 da y s bef ore 
scree ni n g or a d missi o n, or w h o are t o be vacci nate d wit h a C O VI D- 1 9/fl u vacci ne(s)
at a n y ti me d uri n g t he st u d y c o nfi ne me nt peri o d .
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
7.
Partici pati o n i n ot her st u dies i n v ol vi n g st u d y  i nter ve nti o n wit hi n 3 0 da ys or 
5 half -li ves ( w hic he ver is l o n ger) pri or t o st u d y  e ntr y. A partici pa nt ma y be eli gi ble 
e ve n if t he y are i n t he f oll o w-u p p hase of a n i n vesti gati o nal st u d y  as l o n g as t he y 
ha ve n o t recei ve d treat me nt i n t hat st u d y f or at least 1 m o nt h.
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 m a y  be all o we d.
9.
Pre g na nt or breastfee di n g w o me n or e vi de nce of p ositi ve pre g na nc y test at scree ni n g 
or St u d y  D a y  - 1.
1 0. Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V , H Bs A g, 
or H C V A b. He patitis B vacci nati o n is all o we d.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 4
1 1. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at
scree ni n g, as assesse d by t he st u d y-s pecific la b orat or y a n d c o nfir me d by a si n gle
re peat test, if dee me d necessar y:

A S T or A L T le vel ≥1. 5 × U L N;

T bili le vel ≥1. 5 × U L N; partici pa nts wit h a hist or y of Gil bert’s s yn dr o me 
ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or this st u d y
pr o vi de d t he direct bilir u bi n le vel is ≤U L N.
1 2. Re nal i m pair me nt as defi ne d b y  a n e G F R i n a d ults of <7 5 m L / mi n. Base d u p o n 
partici pa nt a ge at scree ni n g, e G F R or e Cr Cl is calc ulate d usi n g t he rec o m me n de d 
f or m ulas i n Secti o n 1 0. 7. 2 t o deter mi ne eli gi bilit y a n d t o pr o vi de a baseli ne t o 
q ua ntif y  a n y s u bse q ue nt ki d ne y safety e ve nts.   
1 3. 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 n ts < 6 0 ye ars; a n d ≥1 5 0/ 9 0 m m H g f or partici pa nts ≥6 0 y ears ol d, f oll o wi n g 
at least 5 mi n utes of s u pi ne rest. If s yst olic B P is ≥ 1 4 0 or 1 5 0 m m H g ( base d o n a ge ) 
or diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of 
t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s eli gi bilit y .
1 4. Scree ni n g s u pi ne s ta 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 or Q R S i nter val > 1 2 0 ms, c o m plete L B B B, si g ns of a n ac ute or 
i n deter mi nate- a ge m y ocar dial i nfarcti o n, S T -T i nter val c ha n ges s u g gesti ve of 
m y ocar dial isc he mia, sec o n d - or t hir d -de gree A V bl oc k, or ser i o us bra d yarr h yt h mias 
or tac h ya rr hyt h mias). If t he u nc orrecte d Q T i nter val is > 4 5 0 ms, t his i nter val s h o ul d 
be rate -c orrecte d usi n g t he Fri dericia met h o d o nl y a n d t he res ulti n g Q Tc F s h o ul d be 
use d f or decisi o n ma ki n g a n d re p orti n g. If Q Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 
1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 3 Q Tc F or Q R S 
val ues use d t o deter mi ne t he partici pa nt’s eli gi bilit y. C o m p uter -i nter prete d E C Gs 
s h o ul d be o verrea d 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.
St u d y Ar ms a n d D ur ati o n:
Eac h partici pa nt will be e nr olle d i n 2 st u d y peri o ds:

Peri o d 1: A n S D of P F -0 7 8 1 7 8 8 3 3 0 0 m g a d mi nistere d orall y i n t he m or ni n g of 
Peri o d 1 D a y  1; a n d

Peri o d 2: Itrac o naz ole 2 0 0 m g a d mi nistere d orall y Q D o n Peri o d 2 Da y s 1- 7, 
i ncl usi ve, as well as P F-0 7 8 1 7 8 8 3 3 0 0 m g a d mi nistere d as a si n gle oral d ose i n t he 
m or ni n g of Peri o d 2 Da y 4 .
Partici pa nts will be disc har ge d o n Peri o d 2 Da y  8 f oll o wi n g c o m pleti o n of all assess me nts.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T he t otal pla n ne d d urati o n of partici pati o n , fr o m t he scree ni n g visit t o t he last f oll o w-u p, is 
a p pr o xi matel y 1 3 wee ks.
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 7 8 1 7 8 8 3
Itrac o naz ole
Ar m N a me
( gr o u p of p artici p a nts recei vi n g a 
s pecific tre atme nt or n o tre at me nt)
Peri o d 1 a n d Peri o d 2
Peri o d 2
U nit D ose Stre n gt h(s)
3 0 0 m g 
2 0 0 m g 
R o ute of A d mi nistr ati o n
Oral
Oral
Use
E x peri me ntal
Pr o be i n hi bit or
I M P or NI M P/ A x M P
I M P
NI M P
St u d y Ar m(s)
Ar m Title
Peri o d 1
Peri o d 2
Ar m Descri pti o n
Partici pa nts will recei ve P F -0 7 8 1 7 8 8 3 
3 0 0 m g a d mi nistere d as a si n gle ora l
d ose , i n t he m or ni n g of Peri o d 1 
Da y 1 
Partici pa nts will recei ve itrac o naz ole 
2 0 0 m g (i n a 2 0-m L s ol uti o n) Q D 
orall y o n Peri o d 2 Da ys 1 - 7, i ncl usi ve, 
as well as P F -0 7 8 1 7 8 8 3 3 0 0 m g
a d mi nistere d as a si n gle oral d ose i n 
t he m or ni n g o n Peri o d 2 Da y 4
St atistic al Met h o ds :
S a m ple Size Deter mi n ati o n
A sa m ple size of 1 0 partici pa nts will pr o vi de a de q uate precisi o n t o esti mate t he effects of 
itrac o naz ole o n t he P K of P F -0 7 8 1 7 8 8 3. T he e x pecte d wi dt hs of t he 9 0 % CI s wit h 8 0 % 
c o vera ge pr o ba bil it y are s h o w n i n t he f oll o wi n g ta ble f or a ra n ge of p ossi ble effects. 
P a r a m eter
Esti m ate d Effect 
( 1 0 0 * Test/ Refere nce)
9 0 % CI
CI Wi dt h
A U C i nf
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
8 7 %, 1 1 5 %
1 3 0 %, 1 7 3 %
1 7 3 %, 2 3 1 %
2 1 7 %, 2 8 8 %
2 6 0 %, 3 4 6 %
3 4 7 %, 4 6 1 %
2 9 %
4 3 %
5 7 %
7 1 %
8 6 %
1 1 4 %
A U C last
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
8 8 %, 1 1 4 %
1 3 2 %, 1 7 0 %
1 7 6 %, 2 2 7 %
2 2 0 %, 2 8 4 %
2 6 4 %, 3 4 1 %
3 5 2 %, 4 5 4 %
2 6 %
3 8 %
5 1 %
6 4 %
7 7 %
1 0 2 %
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 a r a m eter
Esti m ate d Effect 
( 1 0 0 * Test/ Refere nce)
9 0 % CI
CI Wi dt h
C ma x
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
7 9 %, 1 2 7 %
1 1 8 %, 1 9 0 %
1 5 8 %, 2 5 4 %
1 9 7 %, 3 1 7 %
2 3 6 %, 3 8 1 %
3 1 5 %, 5 0 8 %
4 8 %
7 2 %
9 6 %
1 2 0 %
1 4 4 %
1 9 3 %
T hese esti mates are base d o n t he ass u m pti o n t hat wit hi n-partici pa nt sta n dar d de viati o ns 
are
 a n d
 f orl n A U Ci nf, l n A U Clast a n d l n Cma x , res pecti vel y, as o btai ne d 
fr o m o n g oi n g cli nical st u d y C 5 0 9 1 0 0 1  i n healt hy partici pa nts.
T o all o w f or dr o p o uts , a p pr o xi matel y 1 2 partici pa nts will be e nr olle d i n or der t o ha ve 1 0 P K 
e val uable partici pa nts. Partici pa nts w h o wit h dra w fr o m t he st u d y f or n o n-safety reas o ns m a y  
be re place 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.
P h ar m ac o ki netic A n al ysis
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 w h o ta ke at least 1 d ose of 
st u d y i nter ve nti o n a n d i n w h o m at least 1 c o nce ntrati o n val ue is re p orte 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 w h o ta ke at least 1 d ose 
of st u d y  i nter ve nti o n a n d i n w h o m at least 1 of t he P K para meters of pri mar y  i nterest are 
re p orte d.
P K para meters f or P F -0 7 8 1 7 8 8 3 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 use d i n t he deri vati o n of P F-0 7 8 1 7 8 8 3 P K 
para meters w he n a vaila ble, ot her wise n o mi nal ti mes will be use d. T he P F -0 7 8 1 7 8 8 3 plas ma 
P K para meters will be s u m marize d descri pti vel y  b y treat ment. Plas ma c o nce ntrati o ns will be 
liste d a n d s u m marize d b y treat me nt a n d n o mi nal sa m pli n g ti me. I n di vi d ual partici pa nt a n d 
s u m mar y pr ofiles ( mea n a n d me dia n pl ots) of t he plas ma c o nce ntrati o n vers us ti me data will 
be pl otte d usi n g act ual a n d n o mi nal ti mes, res pecti vel y. B o x a n d w his ker pl ots f or A U Clast, 
A U C i nf (if data per mits) a n d C ma x f oll o wi n g a S D of P F -0 7 8 1 7 8 8 3 will be pl otte d b y  
treat me nt.
Dr u g -Dr u g I nter acti o n
Nat ural l o g -tra nsf or me d C ma x a n d A U C i nf (if data per mits, ot her wise A U Clast) val ues of 
P F -0 7 8 1 7 8 8 3 will be a nal y ze d usi n g a mi xe d -effects m o del, wit h treat me nt as fi xe d effect 
a n d partici pa nt as a ra n d o m effect. Esti mates of t he a dj uste d mea n differe nces 
( Test-Refere nce) a n d c orres p o n di n g 9 0 % CIs will be o btai ne d fr o m t he m o del. T he a dj uste d 
me a n differe nces a n d 9 0 % CIs f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates 
of t he rati o of a dj uste d ge o metric mea ns ( Test/ Refere nce) a n d 9 0 % CI f or t he rati os. 
P F -0 7 8 1 7 8 8 3 a d mi nistere d al o ne will be t he Refere nce treat me nt, a n d P F - 0 7 8 1 7 8 8 3 
coa d mi nistere d wit h itrac o naz ole will be t he Test treat me nt.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
S afet y A n al ysis
A Es, E C Gs, B P, P R, R R, a n d safet y la b orat or y  data will be re vie we d a n d s u m marize d o n a n 
o n g oi n g basis d uri n g t he st u d y  t o e val uate t he safet y of t he partici pa nts. A n y cli nical 
la b orat or y, E C G, B P, P R, or R R a b n or malit y of p ote ntial cli nical c o ncer n will be descri be d. 
Safet y  data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d 
descri pti vel y, w here a p pr o priate.
Et hic al C o nsi der ati o ns:
P F -0 7 8 1 7 8 8 3 is n ot e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y partici pa nts i n t his 
st u d y. T his st u d y is desi g ne d pri marily t o f urt her t he u n dersta n di n g of effect of itrac o naz ole 
o n P K of P F - 0 7 8 1 7 8 8 3.
Base d o n preli mi nar y  safet y data fr o m o n g oi n g st u d y C 5 0 9 1 0 0 1, P F-0 7 8 1 7 8 8 3 was safe a n d 
well t olerate d u p t o 4 0 0 0 m g S D a n d u p t o 1 5 0 0 m g BI D d ose re peate d f or 1 0 d a y s.
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 8 1 7 8 8 3 are a vaila ble i n th e c urre nt I B, w hic h is t he S R S D f or t his 
st u d y.
1. 2. Sc he m a
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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.
Peri o d 1 ( P F -0 7 8 1 7 8 8 3 A l o ne): Scree ni n g T hr o u g h Peri o d 1 D a y 5
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
Peri o d 1
E arl y Ter mi n ati o n/ 
Disc o nti n u ati o n
N otes
St u d y D a y 
-2 8 
t o - 2
- 1
1
2
3
4
5

Da y relati ve t o start of st u d y i nter ve nti o n (Peri o d 1 Da y 1).

St u d y Da y 5 is Peri o d 1 Da y 5 a n d Peri o d 2 Da y 1.
Peri o d 1 D a y
- 1
1
2
3
4
5
I nf or me d c o nse nt
X

T o be o btai ne d pri or t o u n der g oi n g a n y st u d y -s pecific pr oce d ures.

See Secti o n 1 0. 1. 2 f or a d diti o nal i nf or mati o n.
P C R U c o nfi ne me nt
X






Partici pa nts will re p ort t o t he P C R U o n St u d y Da y -1, at least 1 2 h o urs pri or t o 
Da y 1 d osi n g i n Peri o d 1 .

Partici pa nt s will be c o nfi ne d bet wee n Peri o d 1 Da y -1 ( St u d y Da y - 1) t o Peri o d 2 
Da y 8 ( St u d y Da y 1 2). 
I ncl usi o n/e xcl usi o n criteria
X
X
Me dical/ me dicati o n hist or y
X  
X

Me dical hist or y will i ncl u de a hist or y of 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 t he p ri or 6 0 da ys. Me dical hist or y will be rec or de d 
at Scree ni n g a n d u p date d o n Da y -1 of Peri o d 1. 
P h ysical e xa m
X  
X

A c o m plete p h ysical e xa m will be perf or me d at Scree ni n g or Da y -1 of Peri o d 1 . A 
brief p h ysical e xa m ma y be perf or me d at ot her ti me p oi nts at t he discreti o n of t he 
i n vesti gat or.
Safet y la b orat or y
X  
X
X  
X

A d diti o nal assess me nts ma y be perf or me d at a n y ti me at t he discreti o n of t he 
i n vesti gat or.

See A p pe n di x 2 f or safet y la bs.
De m o gra p hics (i ncl u di n g hei g ht 
a n d wei g ht)
X
Pre g na nc y test ( W O C B P o nl y)
X
X
X
C o ntrace pti o n c hec k
X
X
X
F S H
X

F or p ost me n o pa usal fe male partici pa nt s o nl y.
Uri ne dr u g testi n g
X
X
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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.
Peri o d 1 ( P F -0 7 8 1 7 8 8 3 A l o ne): Scree ni n g T hr o u g h Peri o d 1 D a y 5
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
Peri o d 1
E arl y Ter mi n ati o n/ 
Disc o nti n u ati o n
N otes
St u d y D a y 
-2 8 
t o - 2
- 1
1
2
3
4
5

Da y relati ve t o start of st u d y i nter ve nti o n (Peri o d 1 Da y 1).

St u d y Da y 5 is Peri o d 1 Da y 5 a n d Peri o d 2 Da y 1.
Peri o d 1 D a y
- 1
1
2
3
4
5
Ser ol o g y: H Bs A g, H Bs A b, 
H C V A b, a n d HI V
X
Vital si g ns
X  
X  
X  
X

Si n gle s u pi ne B P , P R, a n d R R will be perf or me d f oll o wi n g a p pr o xi matel y a 
5 -mi n ute rest i n a s u pi ne p ositi o n
1 2 -Lea d E C G 
X  
X
X

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 uietl y f or 
at least 5 mi n utes i n a s u pi ne p ositi o n .
C O VI D - 1 9 relate d pr oce d ures
X  
X

As per l ocal re g ulati o ns.

See Secti o n 8. 3. 5 .
P F -0 7 8 1 7 8 8 3 a d mi nistrati o n
X
Dr u g - pr o d uct acce pta bilit y 
q uesti o n naire
X

T he q uesti o n naire will be a d mi nistere d after t he d ose of P F -0 7 8 1 7 8 8 3 .
P K bl o o d sa m pli n g f or 
P F -0 7 8 1 7 8 8 3
X
X
X
X
X  
X

See Ta ble 2 .
P K micr o -sa m pli n g ( Tass o®
M 2 0) f or P F-0 7 8 1 7 8 8 3
X

See Ta ble 2 .
Bl o o d/ plas ma rati o sa m ple f or 
P F -0 7 8 1 7 8 8 3
X

See Ta ble 2 .
P K uri ne c ollecti o n f or 
P F -0 7 8 1 7 8 8 3
X
X

See Ta ble 2 .
Retai ne d Researc h Sa m ple f or 
Ge netics ( Pre p D 1)
X

Pre p D 1 Retai ne d Researc h Sa m ples f or Ge netics: 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.
Seri o us a n d n o nseri o us A E
m o nit ori n g
X  
X
X
X
X
X
X  
X

See Secti o n 8. 4 . 3 f or f oll o w-u p A E a n d S A E assess me nts.
Pri or a n d co nc o mita nt 
treat me nt(s)
X  
X
X
X
X
X
X  
X
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 2.
Peri o d 1 ( P F -0 7 8 1 7 8 8 3 Al o ne ): Det aile d S a m pli n g Sc he d ule
Visit I de ntifier 
Tre at me nt Peri o d 1
N otes
Peri o d 1 D a y
1
2 
3 
4 
5
St u d y Da y 5 is Peri o d 1 Da y 5 a n d Peri o d 2 Da y 1.
St u d y D a y
1
2 
3 
4 
5
H o urs Rel ati ve t o D osi n g at 0 h
0
0. 5
1
1. 5
2 
4 
6 
8
1 2
2 4
4 8
7 2
9 6
P F -0 7 8 1 7 8 8 3 a d mi nistrati o n
X
P K bl o o d sa m pli n g f or P F-0 7 8 1 7 8 8 3
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
T he sa m ple at 0 h will be t he p re-d ose P K bl o o d sa m ple .
T he sa m ple o n St u d y Da y 5 s h o ul d be c ollecte d bef ore d osi n g of itrac o naz ole 
of Peri o d 2.
P K micr o -sa m pli n g ( Tass o® M 2 0) f or 
P F -0 7 8 1 7 8 8 3
X  
X  
X  
X  
X
Bl o o d/ plas ma rati o sa m ple f or 
P F -0 7 8 1 7 8 8 3
X
F or details refer t o La b Ma n ual.
P K u ri ne c ollecti o n f or P F -0 7 8 1 7 8 8 3
X








X
T he sa m ple at 0 h will be t he pre -d ose uri ne sa m ple. Uri ne c ollecti o n will 
c o nti n ue u p t o 2 4 h o urs p ost -d ose .
See Secti o n 8. 5. 2 .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 3.
Peri o d 2 ( P F -0 7 8 1 7 8 8 3 Wit h Itr ac o n az ole): D a y 1 T hr o u g h D a y 8
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble 
ma y be f o u n d i n A p pe n di x 1 0 .
Peri o d 2
F oll o w -
u p
E arl y 
Ter mi n ati o n/
Disc o nti n u ati o n
N otes
Peri o d 2 D a y
1
2
3
4
5
6
7
8
2 8 -3 5 
D a ys

F oll o w -u p c o ntact ma y occ ur via tele p h o ne a n d m ust occ ur ar o u n d 2 8 -3 5 da ys 
fr o m a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n.

St u d y Da y 5 is Peri o d 1 Da y 5 a n d Peri o d 2 Da y 1.
St u d y D a y
5
6
7
8
9 1 0 1 1 1 2
P C R U c o nfi ne me nt







X
Safet y la b orat or y
X  
X  
X
X

A d diti o nal safet y la b orat or y assess me nts ma y be perf or me d a n y ti me at t he 
discreti o n of t he in vesti gat or.

See A p pe n di x 2 f or safet y la bs.
C o ntrace pti o n c hec k
X
X
X
Pre g na nc y test ( W O C B P o nl y)
X
X
1 2 -Lea d E C G
X
X

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 uietl y 
f or at least 5 mi n utes i n a s u pi ne p ositi o n.
Vital si g ns
X  
X  
X
X

Si n gle s u pi ne B P , P R, a n d R R will be perf or me d f oll o wi n g a p pr o xi matel y a 
5 -mi n ute rest i n a s u pi ne p ositi o n.
Itrac o naz ole a d mi nistrati o n
X
X
X
X
X
X
X

Partici pa nts will recei ve itrac o naz ole 2 0 0 m g (i n a 2 0 -m L s ol uti o n) Q D .
P F -0 7 8 1 7 8 8 3 a d mi nistrati o n
X

P F -0 7 8 1 7 8 8 3 will be a d mi nistere d orall y, as a 3 0 0 -m g S D .
P K bl o o d sa m pli n g f or 
P F -0 7 8 1 7 8 8 3
X
X
X
X
X
X

See Ta ble 4 f or Peri o d 2 detaile d d osi n g a n d sa m pli n g sc he d ule.
P K Uri ne c ollecti o n f or 
P F -0 7 8 1 7 8 8 3
X
X

See Ta ble 4
Seri o us a n d n o nseri o us A E
m o nit ori n g
X
X
X
X
X
X
X
X  
X
X

See Secti o n 8. 4 . 3 f or f oll o w-u p A E a n d S A E assess me nts.
C o nc o mita nt treat me nt(s)
X
X
X
X
X
X
X
X
X
Disc har ge fr o m P C R U
X

Partici p a nts will be eli gi ble f or disc har ge o n Peri o d 2 Da y 8 at t he discreti o n of 
t he i n vesti gat or f oll o wi n g P K sa m pli n g at 9 6 h o urs after t he last d ose of
P F -0 7 8 1 7 8 8 3 .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 4.
Peri o d 2 ( P F-0 7 8 1 7 8 8 3 Wit h Itr ac o n az ole): Det aile d S a m pli n g Sc he d ule
Visit I de ntifier
Tre at me nt Peri o d 2
N otes
Peri o d 2 D a y
1
2
3
4
5 
6 
7 
8
St u d y Da y 5 is Peri o d 1 Da y 5 a n d Peri o d 2 Da y 1.
St u d y D a y
5
6
7
8
9
1 0
1 1
1 2
H o urs Rel ati ve t o D osi n g of 
P F -0 7 8 1 7 8 8 3 at 0 h o n Peri o d 
2 D a y 4
0
0. 5
1
1. 5
2 
4 
6 
8
1 2
2 4
4 8
7 2
9 6
P F -0 7 8 1 7 8 8 3 a d mi nistrati o n
X
O n Peri o d 2 Da y 4, p artici pa nts will recei ve P F -0 7 8 1 7 8 8 3 3 0 0 m g 
a d mi nistere d orall y i m me diatel y after t he itrac o naz ole d ose f or t hat da y .
Itrac o naz ole a d mi nistrati o n
X
X
X
X
X  
X  
X
Partici pa nts will recei ve itrac o naz ole 2 0 0 m g Q D.
T he itrac o naz ole d osi n g o n Peri o d 2 Da y 1 will ta ke place a p pr o xi matel y 
1 h o ur f oll o wi n g t he last P K sa m ple c ollecti o n o n t hat da y ( 9 6 h o urs p ost d ose 
ti me p oi nt f or Peri o d 1) (Ta ble 2 ).
P K bl o o d sa m pli n g f or 
P F -0 7 8 1 7 8 8 3
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
T he P K bl o o d sa m ple at 0 h will be collecte d pri or t o d osi n g of itrac o naz ole 
a n d P F -0 7 8 1 7 8 8 3.
P K uri ne c ollecti o n f or 
P F -0 7 8 1 7 8 8 3
X








X
T he uri ne sa m ple at 0 h will be c ollecte d pri or t o d osi n g of itrac o naz ole a n d 
P F - 0 7 8 1 7 8 8 3. Uri ne c ollecti o n will c o nti n ue u p t o 2 4 h o urs f oll o wi n g t he d ose 
of P F -0 7 8 1 7 8 8 3 o n Peri o d 2 Da y 4 . See Secti o n 8. 5. 2 .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 3
2. I N T R O D U C TI O N
P F -0 7 8 1 7 8 8 3 is a p ote nt a n d selecti ve i n hi bit or of t he S A R S -C o V - 2 Mpr o t hat is c urre ntly 
bei n g de vel o pe d as a n oral treat me nt f or patie nts wit h C O VI D- 1 9.
2. 1. St u d y R ati o n ale 
T he p ur p ose of t he st u d y  is t o esti mate t he effect of itrac o naz ole, a str o n g C Y P 3 A 4 i n hi bit or, 
o n t he P K of P F -0 7 8 1 7 8 8 3 i n healt h y  a d ults. Res ults fr o m t his st u d y will pr o vi de g ui da nce 
f or d osi n g rec o m me n dati o ns wit h c o nc o mita nt me dicati o ns t hat ha ve C Y P 3 A i n hi bit or y 
p ote ntial .
2. 2. B ac k gr o u n d 
2. 2. 1. Dise ase O ver vie w
I n Dece m ber 2 0 1 9, C O VI D-1 9 was i de ntifie d as a ne w, p ote ntiall y  fatal, res pirat or y i nfecti o n 
ca use d b y t he n o vel c or o na vir us S A R S -C o V -2. T he W H O declare d C O VI D - 1 9 a P u blic 
Healt h E mer ge nc y  of I nter nati o nal C o ncer n o n 2 0 Ja n uar y 2 0 2 0 a n d f urt her c haracterize d t he 
disease o ut brea k as a pa n de mic o n 1 1 Marc h 2 0 2 0. [1 ]
C O VI D -1 9 ma nifests as a wi de ra n ge of ill nesses, fr o m as y m pt o matic i nfecti o n t o se vere 
p ne u m o nia, A R D S, a n d deat h. W hile t he maj orit y of cases (a p pr o xi matel y 8 0 %) are 
as ym pt o matic or mil d, [2 ] patie nts w h o ar e h os pitalize d wit h C O VID -1 9 ma y  e x perie nce 
si g nifica nt m or bi dity a n d m ortalit y[ 3 ],[4 ] a n d are at i ncrease d ris k of de vel o pi n g 
c o m or bi dities s uc h as A R D S, ac ute car diac i nj ur y , t hr o m b oe m b olic e ve nts, a n d/ or ki d ne y 
i nj ur y.[5 ],[6 ],[7 ]
2. 2. 2. C urre nt Tre at me nt O pti o ns
Alt h o u g h m A bs a n d a nti virals ha ve si nce bec o me a vaila ble, t here re mai ns a n i m p orta nt nee d 
t o de vel o p t hera pe utics f or t he treat me nt of C O VI D-1 9 i nfecti o n. Se veral m A bs beca me 
a vaila ble u n der E U As, i ncl u di n g be btel o vi ma b f or treat me nt of mil d t o m o derate C O VI D - 1 9 
i nfecti o n i n select p o p ulati o ns. H o we ver, all m A bs ha ve si nce bee n re m o ve d as treat me nt 
o pti o ns d ue t o di mi nis he d efficac y  wit h t he e mer ge nce of S A R S-C o V -2 varia nts. [8 ]
A nti virals, s uc h as nir matrel vir/rit o na vir a n d re m desi vir I V, are a vaila ble a n d c o nsi dere d 
preferre d t hera pies f or n o n h os pitalize d a d ults, w hile m ol n u pira vi r is c o nsi dere d alter nati ve 
t hera py b y  t he C O VI D-1 9 Treat me nt G ui deli nes Pa nel. [9 ] H o we ver, t hese t hera pe utics are 
li mite d t o o ut patie nt p o p ulati ons wit h mil d t o m o derate C O VI D -1 9 i nfecti o n at ris k f or 
pr o gressi n g t o se vere disease. F urt her m ore, s o me hi g h -ris k patie nts ma y be i neli gi ble f or 
nir matrel vir/rit o na vir d ue t o D DI s, a n d re m desi vir ma y be i naccessi ble f or s o me patie nts as it 
re q uires I V a d mi nistrati o n i n a healt hcare setti n g a n d ret ur ni n g f or t hree s u bse q ue nt da ys f or 
a d diti o nal dail y IV d osi n g.
Des pite t hese a d va nces, t here re mai ns a n i m p orta nt nee d f or a d diti o nal safe a n d effecti ve 
t hera pe utic i nter ve nti o ns t hat d o n ot re q uire a d mi nistratio n i n a healt hcare setti n g, are n ot 
li mite d b y D DIs , a n d ha ve a ris k/ be nefit pr ofile s u p p orti ve of a d mi nistrati o n t o a br oa der 
patie nt p o p ulati o n. T he direct re d ucti o n of viral re plicati o n, t hr o u g h i n hi biti o n of ot her 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
critical viral e nz y m es, offers a n i m p o rta nt mec ha nis m, eit her via a m o n ot hera p y or 
c o m bi nati o n, t o ac hie ve greater patie nt be nefit.
2. 2. 3. R ati o n ale f or De vel o p me nt of P F - 0 7 8 1 7 8 8 3
T he c or o na vir us M pr o is a virall y-e nc o de d e nz yme t hat is critical t o t he S A R S -C o V - 2 
re plicati o n c ycle, a nal o g o us t o ot her o bli gat or y  virall y-e nc o de d pr oteases (e g, HI V pr otease 
or H C V pr otease). M uta ge nesis e x peri me nts wit h ot her c or o na vir uses a n d pic or na vir uses t hat 
are relate d t o S A R S -C o V -2 ( pic or na vir us -li ke s u percl uster) ha ve de m o nstrate d t hat t he 
acti vit y of Mpr o is esse ntial f or viral re plicati o n. N o cl ose h u ma n a nal o gs of c or o na vir us Mpr o
e nz ymes are k n o w n, s u g gesti n g t hat a p pr o priate M pr o i n hi bit ors ma y f u ncti o n as selecti ve 
i n hi bit ors of S A R S-C o V -2 a n d ot her c or o na vir uses as t hera pe utic a ge nts.
I n hi biti o n of t he S A R S-C o V - 2 Mpr o b y  nir matrel vir/rit o na vir has de m o nstrate d t he efficac y 
of a n a nti viral i n t he re d ucti o n of h os pitalizati o n a n d deat h i n mil d t o m o derate C O VI D - 1 9 
patie nts wit h hi g h ris k of pr o gressi o n t o se vere disease.
2. 2. 4. N o ncli nic al O ver vie w
P F - 0 7 8 1 7 8 8 3 is a pote nt (I C 5 0 =  
 µ M; K i =  
 µ M) a n d selecti ve i n hi bit or of 
S A R S -C o V - 2 Mpr o, e x hi biti n g br oa d s pectr u m i n hi bit or y acti vity acr oss t he C or o na viri dae 
fa mil y of Mpr o e nz ymes. T he i n vitr o a nti viral acti vit y  of P F-0 7 8 1 7 8 8 3 a gai nst S A R S -C o V - 2 
was de m o n strate d i n se veral cell li nes. I n all cell ular s yste ms teste d, P F-0 7 8 1 7 8 8 3 
de m o nstrate d p ote nt a nti viral acti vit y  a gai nst S A R S-C o V - 2. P F -0 7 8 1 7 8 8 3 als o e x hi bite d 
a nti viral efficac y a gai nst S A R S-C o V -1, H C o V -2 2 9 E, a n d M E R S -C o V i n cell ular s y ste ms. 
 
 
M ore details are prese nte d i n t he
c urre nt I B.
2. 2. 5. Bi o p h ar m ace utics a n d N o ncli nic al P h ar m ac o ki netics 
2. 2. 5. 1. Bi o p h ar m ace utics
P F -0 7 8 1 7 8 8 3 is a ne utral c o m p o u n d e x hi biti n g m o derate a q ue o us a p pare nt s ol u bilit y  i n 
vari o us bi o -rele va nt me dia a n d l o w passi ve per mea bilit y. I n a preli mi nar y passi ve 
per mea bilit y  assess me nt i n t he R R C K cell li ne, P F-0 7 8 1 7 8 8 3 e x hi bite d a n A -B P a p p of 
0. 5 0 1 0 -6 c m/s, i n dicati n g l o w passi ve per mea bilit y . Preli mi nar y P B P K m o deli n g pre dicts 
sli g ht i m pr o ve me nt (≤2 0 %) i n fracti o n a bs or be d i n fe d vers us faste d state.
2. 2. 5. 2. N o ncli nic al P h ar m ac o ki netics a n d i n vitr o Met a b olis m
P F -0 7 8 1 7 8 8 3 e x hi bite d l o w i n vitr o per mea bilit y  a n d prefere ntially distri b ute d i nt o plas ma 
relati ve t o bl o o d cells. C o nce ntrati o n - de pe n de nt pr otei n bi n di n g was o bser ve d i n ra b bits a n d 
m o n ke y s, w hile n o mea ni n gf ul c o nce ntrati o n bi n di n g was o bser ve d i n h u ma ns at ≤1 0 µ M 
(
). P F-0 7 8 1 7 8 8 3 distri b ute d i nt o t he li ver a n d 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
l u n g t o a greater e xte nt t ha n ot her tiss ues, w hile distri b uti o n i nt o t he brai n was li mite d. 
 
C Y P -me diate d o xi dati o n was t he pri mar y meta b olic r o ute of P F-0 7 8 1 7 8 8 3 i n vitr o a n d i n 
rats. I n vitr o st u dies i n h u ma n li ver micr os o mes i n dicate d meta b olis m of P F-0 7 8 1 7 8 8 3 was 
pre d o mi na ntl y  me diate d b y C Y P 3 A 4 
. 
I n acc or da nce wit h F D A a n d E M A D DI g ui da nce, 
 
 
 
 
 
M ore details are prese nte d i n t he
c urre nt I B.
2. 2. 6. T o xic ol o g y of P F- 0 7 8 1 7 8 8 3
P F - 0 7 8 1 7 8 8 3 was assesse d i n a series of n o ncli nical st u dies. 
T he t o xicit y  of P F-0 7 8 1 7 8 8 3 was e val uate d i n 
 a n d 
 G LP t o xicit y  
st u dies 
 i n 
 a n d 
. T here were 
n o a d verse fi n di n gs i n a n y of t he st u dies. T he N O A E Ls i n t he 
 st u dies 
 
 o ver t he pre dicte d h u ma n u n b o u n d Cma x 
a n d A U C 2 4 at a d ose of 6 0 0 m g BI D.
I n ge neral, t he n o na d verse fi n di n gs i n t he n o n G L P e x pl orat or y st u dies a n d t he G LP pi v otal 
st u dies were si milar.
 
 
 
M ore details are
prese nte d i n t he c urre nt I B.
2. 2. 7. Cli nic al O ver vie w
T he details of desi g n, o bjecti ves a n d e n d p oi nts are detaile d i n t he c urre nt I B. C 5 0 9 1 0 0 1 is 
t he first 6- part o n g oi n g cli nical st u d y usi n g P F-0 7 8 1 7 8 8 3. P K of P F -0 7 8 1 7 8 8 3 was e val uate d 
i n P A R T-1: S A D, P A R T -2: M A D , P A R T-4: M E a n d P A R T -5: D DI  of a n o n g oi n g C 5 0 9 1 0 0 1 
st u d y. P A R T-5: D DI e val uate d t he effect of P F -0 7 8 1 7 8 8 3 o n mi daz ola m P K. I n a d diti o n, P K 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
of P F -0 7 8 1 7 8 8 3 i n Ja pa nese a n d n o n -Ja pa nese p o p ulati o n was c o m pare d i n P A R T-5: D DI . 
T he d oses ra n ge d bet wee n 1 5 0 - 4 0 0 0 m g a n d 2 0 0- 1 5 0 0 m g i n S A D a n d M A D , res pecti vely . 
I n M A D stea dy state P F - 0 7 8 1 7 8 8 3 P K was e val uate d after 1 0 da ys of BI D d osi n g . I n 
P A R T -4: M E 6 0 0 m g P F -0 7 8 1 7 8 8 3 S D was a d mi nistere d t o healt h y a d ult v ol u nteers . 
P A R T -5 e val uate d t he effect of re peat d osi n g of P F -0 7 8 1 7 8 8 3 o n t he meta b olis m of S D 
mi daz ola m .
2. 2. 7. 1. S u m m ar y of P F -0 7 8 1 7 8 8 3 P h ar m ac o ki netics i n H u m a ns
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F urt her details o n t he cli nical P K of P F -0 7 8 1 7 8 8 3 are pr o vi de d i n t he c urre nt I B.
2. 2. 7. 2. S afet y O ver vie w
T he preli m i nar y data c ollecte d as of t he data s na ps h ot ( 1 8 Ja n uar y 2 0 2 3) i n P A R T-1 a n d 
P A R T -2 of t he P hase 1 st u d y ( C 5 0 9 1 0 0 1) de m o nstrate d a n acce pta ble safet y  pr ofile at S Ds
of P F -0 7 8 1 7 8 8 3 or place b o ra n gi n g fr o m 1 5 0 m g t o 4 0 0 0 m g i n P A R T- 1, a n d at d oses of 
2 0 0 m g t o 1 5 0 0 m g BI D of P F-0 7 8 1 7 8 8 3 or place b o f or 1 0 da y s i n P A R T- 2. D ose escalati o n 
st o p pi n g r ules were n ot tri g gere d a n d M T D
was n ot ac hie ve d. T here ha ve bee n n o deat hs, 
S A Es or S U S A Rs re p orte d.
 
 
F urt her details o n t he cli nical saf et y of P F - 0 7 8 1 7 8 8 3 are pr o vi de d i n t he c urre nt I B.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 3. Be nefit/ Ris k Assess me nt
P F -0 7 8 1 7 8 8 3 is n ot e x pecte d t o pr o vi de a ny cli nical be nefit t o healt h y partici pa nts. T his 
st u d y is desi g ne d pri maril y t o esti mate t he effect of m ulti ple d oses of itrac o naz ole o n t he P K 
of P F - 0 7 8 1 7 8 8 3 t o pr o vi de g ui da nce f or d osi n g rec o m me n dati o ns wit h c o nc o mita nt 
me dicati o ns f or P F -0 7 8 1 7 8 8 3.
 
 
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A E s of P F -0 7 8 1 7 8 8 3 ma y  be f o u n d i n t he c urre nt I B, w hic h is t he S R S D f or t his 
st u d y. Re fer 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 . T he S R S D f or t he site s o urce d itrac o naz ole s ol uti o n pr o d uct is t he U S PI.[1 0 ]
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2. 3. 1. Ris k Assess me nt
P ote nti al Ris k of 
Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n(s) P F -0 7 8 1 7 8 8 3
St u d y I nter ve nti o n(s) Itr ac o n az ole
He pat ot o xicit y
Itrac o naz ole has bee n ass ociate d wit h rare cases of 
seri o us he pat ot o xicit y, i ncl u di n g li ver fail ure a n d 
deat h. S o me of t hese cases ha d neit her pre -e xisti n g 
li ver disease n or a seri o us u n derl yi n g me dical 
c o n diti o n, a n d s o me of t hese cases de vel o pe d w it hi n 
t he first wee k of treat me nt. 
S h ort -ter m or i nter mitte nt d osi n g wit h itrac o naz ole (e g, less t ha n 1 4 da ys), is 
ge nerall y c o nsi dere d t o be ass ociate d w it h a l o wer ris k of li ver i nj ur y relati ve 
t o c hr o nic d osi n g. Li ver f u ncti o n will be m o nit ore d. If cli nical si g ns or 
s y m pt o ms de vel o p t hat are c o nsiste nt wit h li ver disease, treat me nt s h o ul d be 
disc o nti n ue d, a n d l i ver f u ncti o n testi n g perf or me d.
Car diac 
d ysr h yt h mias
Life -t hreate ni n g car diac d ysr h yt h mias a n d/ or s u d de n 
deat h ha ve occ urre d i n patie nts usi n g dr u gs s uc h as 
cisa pri de, pi m ozi de, met ha d o ne, or q ui ni di ne 
c o nc o mita ntl y wit h itrac o naz ole a n d/ or ot her C Y P 3 A 4 
i n hi bit ors.
S h ort -ter m d osi n g of itrac o naz ole will be use d i n t his st u d y. C o nc o mita nt use 
of prescri pti o n a n d n o n prescri pti o n dr u gs wit h p ote ntial of i nteracti o n wit h 
itrac o naz ole are n ot all o we d. Partici pa nts wit h u n derl yi n g car diac disease w ill 
be e xcl u d e d. Car diac f u ncti o n will be m o nit ore d. 
Re p orts of 
c o n gesti ve heart 
fail ure
Itrac o naz ole has bee n ass ociate d wit h re p orts of 
c o n gesti ve heart fail ure. I n p ost -mar keti n g e x perie nce, 
heart fail ure was m ore fre q ue ntl y re p orte d i n patie nts 
recei vi n g a t otal dail y d ose of 4 0 0 m g alt h o u g h t here 
were als o cases re p orte d a m o n g t h ose recei vi n g l o wer 
t otal dail y d oses.
T his st u d y will utilize a d ose of 2 0 0 m g dail y. Partici pa nts wit h ris k fact ors 
f or c o n gesti ve heart fail ure are e xcl u de d. E C G a n d vitals will be m o n it ore d.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 3. 2. Be nefit Assess me nt
F or healt h y  partici pa nts i n t his st u d y, n o cli nical be nefit is e x pecte d.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
P F -0 7 8 1 7 8 8 3 is n ot e x pecte d t o pr o vi de a ny cli nical be nefit t o healt h y partici pa nts i n t his 
st u d y.
Ta ki n g i nt o acc o u nt t he meas ures t o mi ni mize ris k t o st u d y partici pa nts , t he p ote ntial ris ks 
i de ntifie d i n ass ociati o n wit h P F - 0 7 8 1 7 8 8 3 are j ustifie d b y t he a ntici pate d be nefits t hat ma y 
be aff or de d t o partici pa nts wit h C O VI D- 1 9 i n f ut ure.
3. O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
Pri m ar y : 
Pri m ar y : 

T o esti mate t he effect of m ulti ple d oses of 
itrac o naz ole 2 0 0 m g Q D o n t he P K of P F - 0 7 8 1 7 8 8 3 
f oll o wi n g a si n gle oral d ose of P F -0 7 8 1 7 8 8 3 3 0 0 m g

P F -0 7 8 1 7 8 8 3 plas ma P K para meters : Cma x a n d A U C i nf (if 
data per mit s, ot her wise A U Clast) wit h itrac o naz ole (test) 
vers us wit h o ut itrac o naz ole (refere nce)
Sec o n d ar y:
Sec o n d ar y : 

T o e val uate t he safet y a n d t olera bilit y of 
P F - 0 7 8 1 7 8 8 3 i n healt h y partici pa nts i n t he a bse nce 
a n d prese nce of m ulti ple d oses of itrac o naz ole

T o c haracterize a d diti o nal P K para meters of 
P F - 0 7 8 1 7 8 8 3 w he n a d mi nistere d al o ne or wit h 
itrac o naz ole i n healt h y partici pa nts

Assess me nt of T E A Es, cli nical la b orat or y a b n or malities, 
vital si g ns, p h ysical e xa ms, a n d 1 2- lea d E C Gs

P F -0 7 8 1 7 8 8 3 plas ma P K para meters: T ma x , a n d if data 
per mits , t½ , C L/ F, Vz/ F, wit h a n d wit h o ut 
c oa d mi nistrati o n of itrac o naz ole
Terti ar y/ E x pl or at or y:
Terti ar y/ E x pl or at or y:

T o assess t he si milarit y of P K i n bl o o d b y 
micr osa m pli n g tec h ni q ue(s) wit h t h ose i n plas ma 
b y ve ni p u nct ure

C o nce ntrati o n of P F -0 7 8 1 7 8 8 3 i n bl o o d a n d plas ma as 
well as P F -0 7 8 1 7 8 8 3 plas ma P K para meters : A U C 1 2, Cma x

T o c haracterize a d diti o nal P K para meters of 
P F -0 7 8 1 7 8 8 3 f oll o wi n g a si n gle oral d ose of 
P F -0 7 8 1 7 8 8 3 wit h a n d wit h o ut itrac o naz ole b y 
re nal f u ncti o n

C o nce ntrati o n of P F -0 7 8 1 7 8 8 3 i n uri ne a n d u ri ne 
P F -0 7 8 1 7 8 8 3 P K para meters: Ae 2 4, C LR , if a p plica ble a n d 
as data per mit s

T o e val uate t he dr u g -pr o d uct acce pta bilit y of 
P F -0 7 8 1 7 8 8 3 

Sc ore o n a 1 4 -ite m dr u g-pr o d uct acce pta bilit y 
q uesti o n naire
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a P hase 1, o pe n la bel, 2- peri o d, fi xe d se q ue nce st u d y t o esti mate t he effect of t he 
str o n g C Y P 3 A 4 i n hi bit or, itrac o naz ole, o n t he plas ma a n d uri ne (if a p plica ble) P K of 
P F - 0 7 8 1 7 8 8 3 i n healt hy a d ult partici pa nts. T he st u d y  will c o nsist of 2 treat me nts: a si n gle 
oral d ose of P F - 0 78 1 7 8 8 3 3 0 0 m g al o ne a n d a si n gle oral d ose of P F -0 7 8 1 7 8 8 3 3 0 0 m g i n 
c o m bi nati o n wit h m ulti ple d oses of itrac o naz ole 2 0 0 m g Q D . A t otal of a p pr o xi matel y 
1 2 he alt h y a d ults will be e nr olle d i nt o t he st u d y  t o e ns ure at least 1 0 partici pa nts c o m plete 
t he st u d y. T he treat me nt will c o nsist of a si n gle fi xe d se q ue nce. Partici pa nts w h o disc o nti n ue 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
fr o m t he st u d y f or n o n-safet y reas o ns ma y be re place d at t he s p o ns or’s discreti o n i n 
c olla b orati o n wit h t he i n vesti gat or. 
Healt h y partici pa nts will be scree ne d t o deter mi ne eli gi bilit y  wit hi n 2 8 da ys pri or t o st u d y 
treat me nt. Me dical hist or y a n d res ults of p hys ical e xa mi nati o n, p h ysical meas ure me nts, vital 
si g ns, 1 2-lea d E C G, a n d cli nical la b orat or y e val uati o ns will deter mi ne eli gi bilit y. 
Partici pa nts will re p ort t o t he P C R U o n Peri o d 1 Da y  - 1 (St u d y  Da y  - 1), at least 1 2 h o urs 
pri or t o Da y  1 d osi n g i n Peri o d 1 a n d will be re q uire d t o sta y i n t he PC R U f or 1 3 d a y s a n d 
1 2 ni g hts .
O n Peri o d 1 D a y  1, eac h e nr olle d partici pa nt will recei ve a si n gle oral d ose of P F - 0 7 8 1 7 8 8 3
3 0 0 m g i n t he m or ni n g of Da y 1. Serial plas ma P K sa m ples will be c ollecte d u p t o 9 6 h o urs 
a n d uri ne will be c ollecte d u p t o 2 4 h o urs after P F -0 7 8 1 7 8 8 3 d ose o n Da y 1. Partici pa nts will 
als o c o m plete a dr u g -pr o d uct acce pta bilit y  q uesti o n naire after recei vi n g P F-0 7 8 1 7 8 8 3 o n 
Peri o d 1 Da y  1 bef ore p ost-d ose plas ma P K sa m ple c ollecti o n.
Partici pa nts will recei ve itrac o naz ole 2 0 0 m g , a d mi nistere d orall y Q D o n Peri o d 2 Da ys 1 
t hr o u g h 7 ( St u d y Da ys 5- 1 1), i ncl usi ve. O n Peri o d 2 Da y 1 t he itrac o naz ole d osi n g will ta ke 
place a p pr o xi matel y 1 ho ur f oll o wi n g t he last P K sa m ple c ollecti o n o n t hat da y ( 9 6 h o urs
p ost -d ose ti me p oi nt). O n Peri o d 2 Da y  4 ( St u d y D a y 8), partici pa nts wi ll recei ve
P F -0 7 8 1 7 8 8 3 3 0 0 m g a d mi nistere d orall y i m me diatel y after t he itrac o naz ole d ose f or t hat 
da y , after w hic h t he partici pa nts will u n der g o serial P K sa m pli n g u p t o 9 6 h o urs a n d uri ne 
will be c ollecte d u p t o 2 4 h o urs f oll o wi n g t he P F - 0 7 8 1 7 8 8 3 d ose o n Peri o d 2 Da y  4. As a 
res ult, t he was h o ut i nter val bet wee n d osi n g of P F- 0 7 8 1 7 8 8 3 i n Peri o d 1 a n d Peri o d 2 is 
7 da y s. Partici pa nts m a y  be c o nfi ne d at t he P C R U d uri n g t he e ntire d urati o n of t he st u d y , a n d 
t he y will be disc har ge d fr o m t he P C R U o n Peri o d 2 Da y 8 ( St u d y D a y 1 2 ) f oll o wi n g 
c o m pleti o n of all assess me nts. 
T he partici pa nts will be faste d o ver ni g ht f or at least 1 0 h o urs bef ore a d mi nistrati o n of 
P F -0 7 8 1 7 8 8 3 ( Peri o d 1 D a y  1 [St u d y  D a y 1] a n d P eri o d 2 D a y 4 [St u d y  D a y 8]). Details of 
meal a n d water restricti o ns al o n g wit h ot her necessities are ela b orate d i n Secti o n 5. 3
Lifest y le C o nsi derati o ns.
If a partici pa nt has a ny cli nicall y si g nifica nt, st u d y-relate d a bn or malities at t he c o ncl usi o n of 
a sc he d ule d i n patie nt p orti o n of t he st u d y , t he Pfizer me dical m o nit or ( or desi g nate d 
re prese ntati ve) s h o ul d be n otifie d a n d t he partici pa nt ma y be as ke d t o re mai n i n t he P C R U 
u ntil s uc h a b n or malities are dee me d n ot cli nica ll y si g nifica nt, or it is safe f or o ut patie nt 
f oll o w-u p.
A f oll o w - u p ( w hic h ma y be a p h o ne call) will be ma de t o partici pa nts a p pr o xi matel y  2 8 t o 
3 5 da y s fr o m a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n.
T he t otal pla n ne d d urati o n of partici pati o n, fr o m t he Scree ni n g visit t o t he last f oll o w-u p, is 
a p pr o xi matel y 1 3 wee ks.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
As P F -0 7 8 1 7 8 8 3 is pri maril y  meta b olize d b y C Y P 3 A, a str o n g i n hi bit or of t hat e nz yme (e g,
itrac o naz ole) is e x pecte d t o i ncrease t he s ys te mic e x p os ure of P F-0 7 8 1 7 8 8 3. Itrac o naz ole a n d 
its pri mar y meta b olite ( h ydr o x y -itrac o naz ole) are s pecific str o n g i n hi bit ors of C Y P 3 A. F or 
t hese c haracteristics, al o n g wit h its safety pr ofile, itrac o naz ole has ofte n bee n utilize d as a 
per petrat or dr u g f o r C Y P 3 A i n hi biti o n P K dr u g i nteracti o n st u dies.[1 1 ] Gi ve n t he 
meta b olis m pr ofi le of P F - 0 7 8 1 7 8 8 3, c o nc o mita nt a d mi nistrati o n of m ulti ple d oses of 
itrac o naz ole al o n g wit h P F - 0 7 8 1 7 8 8 3 m a y  lea d t o i ncrease d s yste mic e x p os ure of
P F -0 7 8 1 7 8 8 3. I n t he pr o p ose d st u d y, i n Peri o d 2, itrac o naz ole will be a d mi nistere d as a 
s ol uti o n ( 2 0 0 m g Q D) f or 3 d a y s pri or t o c oa d mi nistrati o n wit h P F-0 7 8 1 7 8 8 3 ( Peri o d 2 Da y  
4). Alt h o u g h 3 d a y s is i ns ufficie nt f or attai n me nt of stea dy state of itrac o naz ole (effecti ve 
half -life of 2 4 h) ,[1 2 ] t he 3-d a y  lea d-i n all o ws f or s o me acc u m ulati o n, wit h hi g her 
itrac o naz ole a n d t he meta b olite e x p os ure a n d t heref ore a p ote ntiall y  greater de gree of 
C Y P 3 A i n hi biti o n . D osi n g itrac o naz ole f or l o n ger t ha n 3 da y s pri or t o c oa d mi nistrati o n wit h 
a C Y P 3 A s u bstrate di d n ot a p pear t o pr o vi de a d diti o nal i n hi bit or y  effect.[1 3 ]
 
 
Wit h C Y P 3 A i n hi biti o n , t he half-life of P F-0 7 8 1 7 8 8 3 is a ntici pate d t o i ncrease. I n or der t o 
s ufficie ntl y ca pt ure t he eli mi nati o n p hase, i n b ot h peri o ds of t he pr o p ose d st u d y, P K 
sa m pli n g will c o nti n ue u ntil 9 6 h o urs p ost P F - 0 7 8 1 7 8 8 3 dose. P K micr osa m pli n g will be 
e x pl ore d i n Peri o d 1 t o e xa mi ne c o nc or da nce bet wee n c o nce ntrati o ns of P F- 0 7 8 1 7 8 8 3 
meas ure d i n t he tra diti o nal P K sa m ples v ers us t he micr osa m ples. M ulti ple micr osa m ples 
c ollecte d f oll o wi n g t he P F -0 7 8 1 7 8 8 3 d ose i n Peri o d 1 w o ul d all o w f or A U C calc ulati o n s. If 
t he c o nc or da nce is f o u n d t o be acce pta ble, i n f ut ure st u dies, micr osa m pli n g has a p ote ntial t o 
decrease st u d y b ur de n o n patie nts . Esti mate of t he bl o o d/ plas ma rati o is esse ntial as it is use d 
as a scali n g fact or t o esti mate t he c o nc or da nce bet wee n t he c o nce ntrati o n of P F- 0 7 8 1 7 8 8 3 
meas ure d t hr o u g h 2 sa m pli n g met h o ds.
T here will be at least 7 da y s bet wee n t he a d mi nistrati o n of 2 S Ds of P F -0 7 8 1 7 8 8 3, e ns uri n g 
n o carr y -o ver effect fr o m Peri o d 1 t o Peri o d 2. A st u d y  desi g n wit h multi ple d oses of t he 
st u d y i nter ve nti o n is c o nsi dere d f or a victi m D DI st u d y pri marily w he n t here is a n i n dicati o n 
of ti me -de pe n de nt P K .[1 3 ] Base d o n t he data at ha n d, t here is n o e vi de nce of a n y discer ni ble 
ti me-de pe n de nt P K f or P F- 0 7 8 1 7 8 8 3, a n d t h us a n S D a d mi nistrati o n of P F - 0 7 8 1 7 8 8 3 al one 
a n d i n prese nce of itrac o naz ole is dee me d s uita ble.
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
St u dies t o e val uate t he de vel o p me ntal t o xicit y  of P F-0 7 8 1 7 8 8 3 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 ).
4. 3. J ustific ati o n f or D ose
T his st u d y  is desi g ne d t o esti mate t he effect of m ulti ple-d ose a d mi nistrati o n of itrac o naz ole 
2 0 0 m g Q D o n t he P K of P F -0 7 8 1 7 8 8 3 3 0 0 m g S D .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A d ose of 3 0 0 m g  P F -0 7 8 1 7 8 8 3 is t o be a d mi nistere d orall y wit h a n d wit h o ut itrac o naz ole. 
 
 
 
 
T here ha ve bee n n o deat hs, S A Es or S U S A Rs re p orte d. M T D
was n ot
ac hie ve d. 
 
 
 
 
Effecti ve t ½ of P F -0 7 8 1 7 8 8 3 is esti mate d t o be a p pr o xi matel y 
h o urs i n prese nce of itrac o naz ole. P F - 0 78 1 7 8 8 3 will be a d mi nistere d u n der fasti n g 
c o n diti o n i m me diatel y after t he a d mi nistrati o n of itrac o naz ole o n Peri o d 2 Da y 4 t o 
ma xi mize itrac o naz ole s yste mic e x p os ures a n d C Y P 3 A 4 i n hi biti o n. F o o d will n ot be gi ve n at 
least 1 0 h o urs bef ore a n d 4 h o urs after all st u d y i nter ve nti o ns o n Peri o d 2 Da y  4. 
Itrac o naz ole is a well-acce pte d C Y P 3 A 4 i n hi bit or i n D DI st u dies gi ve n its str o n g i n hi biti o n 
p ote ntial, l o w Q Tc pr ol o n gati o n ris k, a n d fa v ora ble safet y pr of ile.[1 3 ] I n Peri o d 2, oral d ose s
of itrac o naz ole 2 0 0 m g s ol uti o n a d mi nistere d Q D f or 7 d a y s will be use d t o pr o vi de a 
s u bsta ntial de gree of C Y P 3 A 4 i n hi biti o n. D oses greater t ha n 2 0 0 m g  are n ot e x pecte d t o 
pr o vi de a n y a d diti o nal C Y P 3 A 4 i n hi biti o n. [1 3 ] Oral s ol uti o n of itrac o naz ole u n der faste d 
state is re p orte d t o ha ve hi g her s ys te mic e x p os ure a n d l o wer varia bilit y.[1 3 ] Itrac o naz ole will 
c o nti n ue t o be a d mi nistere d o n Peri o d 2 Da y s 5-7 t o mai ntai n C Y P 3 A 4 i n hi biti o n u ntil 
c o m pleti o n of P K sa m pli n g. S h ort -ter m d osi n g wit h itac o naz ole (ie, ≤1 4 da y s), as pr o p ose d
i n t his D DI  st u dy , is ge nerall y c o nsi dere d t o be safe.[1 3 ]
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 t he 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 b ot h 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 e t 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, r ace, a n d et h nicit y. T he f oll o wi n g eli gi bilit y  
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
criteria are desi g ne d t o select partici pa nt s f or w h o m partici pati o n i n t he st u d y  is c o nsi dere d 
a p pr o priate. All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het he r a partic ular partici pa nt is s uita ble f or t his pr ot oc ol.
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria , als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:
A ge a n d Se x :
1.
Male a n d fe male partici pa nts
a ge d 1 8 t o 6 5 years of a ge, i ncl usi ve, at scree ni n g w h o 
are o vertl y healt h y as deter mi ne d by me dical e val uati o n i ncl u di n g me dical hist or y, 
p h y sical e xa mi nati o n, la b orat or y tests, a n d sta n dar d 1 2-lea d E C G.
Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts.
Ot her I ncl u si o n Criteri a: 
2.
B MI of 1 7. 5 t o 3 2 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.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt .
4.
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.
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.
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.
2.
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, C V , he patic, psyc hiatric, ne ur ol o gic al, or aller gic disease 
(i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as ym pt o matic, seas o nal aller gies at 
t he ti me of d osi n g) a n d, i n t he j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he 
partici pa nt i na p pr o priate f or e ntr y  i nt o t his st u d y.
3.
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).
4.
P osi ti ve test res ult f or S A R S-C o V -2 i nfecti o n at a d missi o n. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Pri or/ C o nc o mit a nt T her a p y:
5.
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 2 8 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 (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 ).
6.
Partici pa nts w h o ha ve recei ve d a C O VI D - 1 9/fl u vacci ne(s) wit hi n 7 da y s bef ore 
scree ni n g or a d missi o n, or w h o are t o be vacci nate d wit h a C O VI D- 1 9/fl u vacci ne(s)
at a n y ti me d uri n g t he st u d y c o nfi ne me nt peri o d .
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
7.
Partici pati o n i n ot her st u dies i n v ol vi n g st u d y  i nter ve ntio n wit hi n 3 0 da y s or 
5 half -li ves (w hic he ver is l o n ger) pri or t o st u d y  e ntr y. A partici pa nt ma y be eli gi ble 
e ve n if t he y are i n t he f oll o w-u p p hase of a n i n vesti gati o nal st u d y  as l o n g as t he y 
ha ve n ot recei ve d treat me nt i n t hat st u d y  f or at least 1 m o nt h. 
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 m a y  be all o we d.
9.
Pre g na nt or breastfee di n g w o me n or e vi de nce of p ositi ve pre g na nc y test at scree ni n g 
or St u d y  D a y  - 1.
1 0. Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V, H Bs A g, 
or H C V A b. He patitis B vacci nati o n is all o we d.
1 1. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
Scree ni n g as assesse d b y t he st u d y-s pecific la b orat or y a n d c o nfir me d b y a si n gle 
re peat, if dee me d necessar y: 

A S T or A L T le vel ≥1. 5 × U L N; 

T bili 1. 5 × U L N; partici pa nts wit h a hist or y  of Gil bert's sy n dr o me ma y  ha ve a 
direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y  pr o vi de d t he direct 
bilir u bi n is U L N.
1 2. Re nal i m pair me nt as defi ne d b y  a n e G F R i n a d ults of < 7 5 m L/ mi n. Base d u p o n 
partici pa nt a ge at scree ni n g, e G F R or e Cr Cl is calc ulate d usi n g t he rec o m me n de d 
f or m ulas i n Secti o n 1 0. 7. 2 t o deter mi ne eli gi bilit y a n d t o pr o vi de a baseli ne t o 
q ua ntif y  a n y s u bse q ue nt ki d ne y safety e ve nts.
1 3. Scree ni n g s u pi ne B P ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g ( diast olic) f or 
partici pa nts < 6 0 ye ars; a n d ≥1 5 0/ 9 0 m m H g f or partici pa nts ≥6 0 y ears ol d, f oll o wi n g 
at least 5 mi n utes of s u pi ne rest. If s yst olic B P is ≥ 1 4 0 or 1 5 0 m m H g ( base d o n a ge ) 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
or diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of 
t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s eli gi bilit y .  
1 4. Scree ni n g s u pi ne st a 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 safety or i nter pretati o n of st u d y res ults (e g, 
Q Tc F > 4 5 0 ms or Q R S i nter val > 1 2 0 ms, c o m plete L B B B, si g ns of a n ac ute or 
i n deter mi nate- a ge m y ocar dial i nfarcti o n, S T -T i nter val c ha n ges s u g gesti ve of 
m y ocar dial isc he mia, sec o n d - or t hir d -de gree A V bl oc k, or seri o us bra d y arr h yt h mias 
or tac h ya rr hyt h mias). If t he u nc orrecte d Q T i nter val is > 4 5 0 ms, t his i nter val s h o ul d 
be rate -c orrecte d usi n g t h e Fri dericia met h o d o nl y a n d t he res ulti n g Q Tc F s h o ul d be 
use d f or decisi o n ma ki n g a n d re p orti n g. If Q Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 
1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 3 Q Tc F or Q R S 
val ues use d t o deter mi ne t he partici pa nt’ s eli gi bilit y. C o m p uter-i nter prete d E C Gs 
s h o ul d be o verrea d 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.
Ot her E xcl usi o n Criteri a:
1 5. H y perse nsiti vit y  or pre vi o us seri o us/si g nifica nt A Es d ue t o az ole a ntif u n gals.
1 6. Ha ve a n y m e dical c o n diti o ns, me dical hist or y, or are ta ki n g a ny m e dicati o ns t hat are 
c o ntrai n dicate d i n t he itrac o naz ole prescri bi n g i nf or mati o n.
1 7. Hist or y  of alc o h ol a b use or bi n ge dri n ki n g a n d/ or a n y ot her illicit dr u g use or 
de pe n de nce wit hi n 6 m o nt hs of Scree ni n g. Bi n ge dri n ki n g is defi ne d as a patter n of 
5 ( male) a n d 4 (fe male) or m ore alc o h olic dri n ks i n a b o ut 2 h o urs. As a ge neral r ule, 
alc o h ol i nta ke s h o ul d n ot e xcee d 1 4 u nits per wee k ( 1 u nit = 8 o u nces ( 2 4 0 m L ) beer, 
1 o u nce ( 3 0 m L) of 4 0 % s pirit, or 3 o u nces ( 9 0 m L) of wi ne).
1 8. 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 9. Use of t o bacc o or nic oti ne -c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nts of 
5 ci garettes per da y or 2 c he ws of t o bacc o per da y.
2 0. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir famil 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 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
a n d t heir part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see A p pe n di x 4 , 
Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. T he i n vesti gat or or desi g nee will a d vise t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  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 acce pta ble effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectly a n d d oc u me nt 
t he c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart. Partici pa nts nee d 
t o affir m t heir c o nsiste nt a n d c orrect use of at least 1 of t he selecte d met h o ds of 
c o ntrace pti o n, c o nsi deri n g t hat t heir ris k f or pre g na nc y  ma y ha ve c ha n ge d si nce t he last visit. 
I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he partici pa nt t o call i m me diatel y if t he 
selecte d c o ntrace pti o n met h o d is disc o nti n ue d a n d d oc u me nt t he re q uire me nt t o use a n 
alter nate pr ot oc ol-s pecifie d met h o d, i ncl u di n g if t he partici pa nt will n o l o n ger use a bsti ne nce 
as t he selecte d c o ntrace pti o n met h o d, or if pre g na nc y is k n o w n or s us pecte d i n t he partici pa nt 
or part ner.
5. 3. 2.
Me als a n d Diet ar y Restricti o ns

Partici pa nt s m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt water) at least 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 dr u g a d mi nistrati o n f or:

D osi n g of itrac o naz ole o n Peri o d 2 Da y  4

M or ni n g P F - 0 7 8 1 7 8 8 3 a d mi nistrati o n o n Peri o d 1 Da y 1 a n d Peri o d 2 Da y 4. 

O n da y s w he n itrac o naz ole is a d mi nistere d al o ne, partici pa nts will be faste d at least 
4 h o urs o ver ni g ht bef ore a d mi nistrati o n. Brea kfast will be pr o vi de d a p pr o xi matel y
1 h o ur after itrac o naz ole d osi n g. Water ma y  be c o ns u me d wit h o ut restricti o n.

Water is per mitte d u ntil 1
h o ur pri or t o st u d y i nter ve nti o n a d mi nistrati o n.
Water ma y 
be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur after P F - 0 78 1 7 8 8 3 m or ni n g d osi n g 
o n P K da y s (Peri o d 1 D a y 1, P eri o d 2 D a y 4). 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 t he last d ose of t he m or ni n g of 
eit her itrac o naz ole or P F - 0 78 1 7 8 8 3 , e g, after P F -0 7 8 1 7 8 8 3 d osi n g o n Peri o d 2 Da y 4.

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 t he last d ose of t he 
m or ni n g of eit her itrac o naz ole or P F -0 7 8 1 7 8 8 3 , e g, after P F-0 7 8 1 7 8 8 3 d osi n g o n 
Peri o d 2 Da y  4.

A n e ve ni n g s nac k m a y be per mitte d .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi ne, gra pefr uit, or gra pefr uit -relate d 
citr us fr uits (e g, Se ville ora n ges, p o mel os, fr uit j uices) fr o m 7 d a y s pri or t o t he first 
d ose of st u d y i nter ve nti o n u ntil c ollecti o n of t he fi nal P K bl o o d sa m ple.  

W hile partici pa nts are c o nfi ne d, t he ir t otal dail y n utriti o nal c o m positi 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.
5. 3. 3. C affei ne, Alc o h ol, a n d T o b acc o

Partici pa nt s will a bstai n fr o m caffei ne-c o ntai ni n g pr o d ucts f or 2 4 h o urs pri or t o t he 
start of d osi n g u ntil c ollecti o n of t he fi nal P K sa m ple of eac h st u d y  peri o d.  

Partici pa nt s will a bstai n fr o m alc o h ol f or 2 4 h o urs pri or ( or as s pecifie d a b o ve f or re d 
wi ne) t o a d missi o n t o t he P C R U a n d c o nti n ue a bstai ni n g fr o m alc o h o l u ntil c ollecti o n 
of t he fi nal P K sa m ple of eac h st u d y peri o d. Partici pa nt s ma y u n der g o a n alc o h ol 
breat h test or bl o o d alc o h ol test at t he discreti o n of t he i n vesti gat or.

Partici pa nt s will a bstai n fr o m t he use of t o bacc o or nic oti ne-c o ntai ni n g pr o d ucts f or 
2 4 h o urs pri or t o d osi n g a n d d uri n g c o nfi ne me nt i n t he P C R U.
5. 3. 4. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea v y lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c ollecti o n f or cli nical 
la b orat or y tests. Wal ki n g at a n or mal pace will be per mitte d;

I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P , P R , a n d E C G 
meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 
4 h o urs after m or ni n g d osi n g , a n d ma y be re q uire d t o f oll o w meals a n d dietar y 
restricti o ns.
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 failure) ma y  be 
rescree ne d. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal a n d n o ni n vesti gati o nal me dici nal 
pr o d ucts, me dical de vices, a n d ot her i nter ve nti o ns (e g, s ur gical a n d be ha vi oral) i nte n de d t o 
be a d mi nistere d t o t he st u d y partici pa nts d uri n g t he st u d y c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o P F -0 7 8 1 7 8 8 3 or itrac o naz ole .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 7 8 1 7 8 8 3
Itrac o naz ole
Ar m N a me
( gr o u p of p artici p a nts recei vi n g a 
s pecific tre atme nt or n o 
tre atme nt)
Peri o d 1 a n d 2
Peri o d 2
T y pe
Dr u g
Dr u g
D ose F or m ul ati o n
Ta blet
S ol uti o n
U nit D ose Stre n gt h(s)
3 0 0 m g
2 0 0 m g
D os a ge Le vel(s)
3 0 0 m g S D ( Peri o d s 1 a n d 2)
2 0 0 m g Q D f or 7 da ys
R o ute of A d mi nistr ati o n
Oral
Oral
Use
E x peri me ntal
Pr o be i n hi bit or
I M P or NI M P/ A x M P
IM P
N I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or
Pr o vi de d l ocall y b y t he P C R U
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d 
as o pe n -la bel s u p pl y i n b ul k b ottles 
al o n g wit h i n di vi d ual d ose 
c o ntai ners, f or u nit d osi n g. Eac h 
c o ntai ner will be la bele d as re q uire d 
per c o u ntr y re q uire me nt.
St u d y i nter ve nti o n will be pr o vi de d i n its 
o w n c o m mercial co ntai ner. Eac h c o ntai ner 
will be la bele d as re q uire d per c o u ntr y 
re q uire me nt.
S R S D
I B f or P F-0 7 8 1 7 8 8 3
U S PI f or itrac o naz ole s ol uti o n
C urre nt N a me
P F -0 7 8 1 7 8 8 3
As a vaila ble l ocall y
St u d y Ar m(s)
A r m  Title
Peri o d 1
Peri o d 2
A r m  Descri pti o n
Partici pa nts will recei ve 
P F -0 7 8 1 7 8 8 3 3 0 0 m g 
a d mi nistere d as a si n gle oral d ose, 
i n t he m or ni n g of Peri o d 1 Da y 1
Partici pa nts will recei ve 
itrac o naz ole 2 0 0 m g (i n a 2 0-m L 
s ol uti o n) Q D orall y o n Peri o d 2 
Da y s 1- 7, i ncl usi ve, as well as 
P F -0 7 8 1 7 8 8 3 3 0 0 m g 
a d mi nistere d as a si n gle oral d ose 
i n t he m or ni n g o n Peri o d 2 Da y 4. 
P F - 0 7 8 1 7 8 8 3 ta blets will be s u p plie d t o t he PC R U i n b ul k al o n g wit h i n di vi d ual d osi n g 
c o ntai ners f or u nit d osi n g. Itrac o naz ole ( S p ora n o x® ) oral s ol uti o n 1 0 m g/ m L will be 
s u p plie d l ocall y b y  t he P C R U.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
6. 1. 1. A d mi nistr ati o n
St u d y  i nter ve nti o ns will be a d mi nistere d orall y  a n d acc or di n g t o t he c o n diti o ns descri be d i n 
t he S o A secti o n a n d Pr ot oc ol Secti o n 5. 3. 2 Meals a n d Dietar y  Restricti o ns.
O n Peri o d 1 Da y  1, f oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nt s will recei ve 
P F - 0 7 8 1 7 8 8 3 3 0 0 m g a d mi nistere d orall y i n t he m or ni n g of Peri o d 1 Da y 1.
C oa d mi nistrati o n: O n P eri od 2 D a y 4, t he d ose of P F -0 7 8 1 7 8 8 3 3 0 0 m g s h o ul d 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 a n d i m me diatel y after t he 
a d mi nistrati o n of t he d ose of itrac o naz ol e 2 0 0 m g . I nvesti gat or site pers o n nel will a d mi nister 
P F -0 7 8 1 7 8 8 3 wit h a m bie nt te m perat ure water t o a t otal v ol u me of a p pr o xi matel y  2 4 0 m L. 
O n Peri o d 2 Da y s 1 t hr o u g h 7 , partici pa nts will recei ve itrac o naz ole 2 0 0 m g (i n a 2 0 -m L  
s ol uti o n) Q D orall y. I n vesti gat or site pers o n nel will a d mi nister itrac o naz ole wit h a m bie nt 
te m perat ure water t o a t otal v ol u me of a p pr o xi matel y 2 4 0 m L.
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 
1 h o ur b y  a n a p pr o priatel y q ualifie d a n d trai ne d me m ber of t he st u d y staff. A p pr o priate 
me dicati o n a n d ot her s u p p orti ve meas ures f or ma na ge me nt of a me dical e mer ge nc y  will be 
a vaila ble i n acc or da nce wit h l ocal g ui deli nes a n d i nstit uti o nal g ui deli nes.
6. 2. Pre p ar ati o n , H a n dli n g , St or a ge , a n d Acc o u nt a bilit y
1.
T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate c o n diti o ns (e g, 
te m perat ure) ha ve bee n mai ntai ne d d uri n g tra nsit f or all st u d y  i nter ve nti o ns recei ve d 
a n d a n y discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st ud y  i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y, pre pare, a n d/or a d mi nister st u d y  i nter ve nti o n.
3.
All st u d y  i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d 
m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d 
st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. At 
a mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s must 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures si nce pre vi o usly d oc u me nte d u p o n 
ret ur n t o b usi ness.
4.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h acti o ns ta ke n. T he site s h o ul d acti vely 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o on 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
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
re p ort f or eac h exc ursi o n will be pr o vi de d t o t he site i n t he P 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 v esti gat or, i nstit uti o n, hea d of t he me dical i nstit uti o n ( w here a p plica ble) , or 
a ut h orize d site staff is res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y, 
rec o nciliati o n, a n d rec or d mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal 
dis p ositi o n rec or ds) , s uc h as t he IP A L  or s p o ns or-a p pr o ve d e q ui vale nt . All st u d y  
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 the P 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 oye d i n 
c o m plia nce wit h a p plica ble e n vir o n me ntal r e 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 or
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 these acti vities.
See t he P C R U l ocal/site pr oce d ures f or P F-0 7 8 1 7 8 8 3 f or i nstr ucti o ns o n h o w t o pre pare t he 
st u d y i nter ve nti o n f or a d mi nistrati o n. C o m mercial itrac o naz ole ( e g, S p ora n o x ® or a n
e q ui vale nt ge neric pr o d uct ) oral s ol uti o n will be dis pe nse d at t he P C R U i nt o oral s yri n ges
usi n g t he pac ka ge i nsert as g ui da nce. All s t u d y i nter ve nti o n s h o ul d be pre pare d a n d 
dis pe nse d b y  a n a p pr o priatel y q ualifie d a n d e x perie nce d me m ber of t he st u d y staff (e g, 
p h y sicia n, n urse, p h ysicia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or 
p har macist) as all o we d b y  l ocal, state, a n d i nstit uti o nal g ui da nce. A sec o n d staff me m ber will 
verif y  t he dis pe nsi n g.
6. 3. Assi g n me nt t o St u d y I n ter ve nti o n
T he i n vesti gat or will assi g n partici pa nt n u m bers t o t he partici pa nts as t he y  are scree ne d f or 
t he st u d y. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
6. 4. Bli n di n g
T his is a n o pe n -la bel st u d y. 
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n 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. St u d y site pers o n nel will e xa mi ne eac h 
partici pa nt’s m o ut h t o e ns ure t hat t he st u d y  i nter ve nti o n was i n geste d.
6. 6. D ose M o dific ati o n
N o d ose m o dificati o n is a ntici pate d.
6. 7. C o nti n ue d Access t o S t u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y partici pati o n.
6. 8. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of P F -0 7 8 1 7 8 8 3 a n d itrac o naz ole greater t ha n 
m g a n d 4 0 0 m g , 
res pecti vely, wit hi n a 2 4- h o ur ti me peri o d ± 2 h o urs will be c o nsi dere d a n o ver d ose.
T here is n o s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d:
1.
C o ntact t he st u d y me dical m o nit or wit hi n 2 4 h o urs.
2.
Cl osel y  m o nit or t he partici pa nt f or a n y 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.
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 1 da y fr o m t he date of t he last d ose of 
st u d y i nter ve nti o n if re q ueste d b y t he st u d y me dical m o nit or ( deter mi ne d o n a 
case-b y -case basis).
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he st u d y me dical m o nit or as nee de d base d o n t he cli nical e val uati o n of t he 
partici pa nt.
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 2 8 da ys or 5 h alf-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 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 . Aceta mi n o p he n/ paraceta m ol ma y  be use d at d oses of 
≤1 g/ da y .
H or m o nal c o ntrace pti ves t hat meet t he re q uire me nts of t his st u d y  are all o we d t o be use d i n 
partici pa nts w h o are W O C B P (see A p pe n di x 4 ).
All c o nc o mita nt treat me nts ta ke n d uri n g t he st u d y  m ust be rec or de d wit h i n dicati o n, dail y 
d ose, a n d start a n d st o p dates of a d mi nistrati o n. All partici pa nts will be q uesti o ne d a b o ut 
c o nc o mita nt treat me nt at eac h cli nic visit.
Treat me nts ta ke n wit hi n 2 8 da y s bef ore t he first d ose of st u d y i nter ve nti o n will be 
d oc u me nte d as a pri or treat me nt. Treat me nts ta ke n after t he first d ose of st u d y  i nter ve nti o n 
will be d oc u me nte d as c o nc o mita nt treat me nts.
6. 9. 1. Resc ue Me dici ne
T here is n o resc ue t hera p y t o re verse t he A Es o bser ve d wit h P F- 0 7 8 1 7 8 8 3 or itrac o naz ole. 
Sta n dar d me dical s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es.
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o nti n u ati o n of St u d y I nter ve nti o n
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue st u d y i nter ve nti o n. Reas o ns 
f or per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n i ncl u de t he f oll o wi n g:

A E re q uiri n g disc o nti n uati o n i n t he i n vesti gat or’s vie w,

Pre g na nc y ,

P os iti ve C O VID- 1 9 test.
If st u d y i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt will n ot re mai n i n t he st u d y  
f or f urt her e val uati o n. See t he S o A f or data t o be c ollecte d at t he ti me of disc o nti n uati o n of 
st u d y i nter ve nti o n.
7. 1. 1. P ote nti al C ases of Ac ute Ki d ne y I nj ur y
Partici pa nts e x p ose d t o I M P de m o nstrati n g tra nsie nt or s ustai ne d i ncrease i n Screat ( wit h 
decrease i n Screat - base d e G F R or e Cr Cl) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter- me diate d effect relate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
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 nti ati 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ments 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates o f e G F R, e Cr Cl a n d Screat-base d e G F R a n d c o m bi ne d 
Screat -S c y s-base d e G F R s h o ul d als o be deri ve d usi n g t he a p pr o priate e q uati o n descri be d i n 
A p pe n di x 7 .
Differe nti ati n g Ac ute Ki d ne y I nj ur y fr o m DI CI
A c o nfir me d Screat i ncrease is defi ne d as:
(i) ≥0. 3 m g/ d L ( ≥2 6. 5 µ m ol/ L) wit hi n 4 8 h o urs O R 
(ii) c o nfir me d Screat i ncrease ≥1. 5 ti mes baseli ne ( k n o w n or s us pecte d t o ha ve occ urre d 
wit hi n t he pri or 7 da y s). 
Base d o n t he assess me nts perf or me d, s us pecte d A KI (i ncl u di n g DI KI) ma y be differe ntiate d 
fr o m DI CI as f oll o ws.
A d ult p artici p a nts
A KI (i ncl u di n g DI KI)
A n y o ne of t he bel o w
DI CI
Sc ys & Screat
Si m ulta ne o us, c o nfir me d ser u m c ystati n 
C ( Sc ys) i ncrease a n d c o nfir me d Screat 
i ncrease 
C o nfir me d Screat i ncrease wit h o ut 
c o nfir me d i ncrease i n refle x Sc ys 
A N D 
C o nfir me d Screat -base d e G F R 
decrease w it h o ut c o nfir me d c o m bi ne d 
Screat -Sc ys -base d e G F R decrease.
e G F R
Decrease i n Screat -base d e G F R a n d 
c o m bi ne d Screat -Sc ys -base d e G F R ( w he n 
a vaila ble)
Al b u mi n uria or 
pr otei n uria
C o nfir me d al b u mi n uria i ncrease (see 
A p pe n di x 7 f or Gra des A 1 t o A 3 
q ua ntitati o n)
Uri ne v ol u me
Uri ne v ol u me < 0. 5 m L/ k g/ h f or 
6 c o nsec uti ve h o urs
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 4
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is (i) ne w-o nset or w orse ni n g al b u mi n uria or pr otei n uria are 
detecte d.
All c o nfir me d cases of cli nicall y  rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d 
p ote ntial cases of DI KI if n o ot her reas o n f or t he ki d ne y f u ncti o n a b n or malities has bee n 
f o u n d.
If a p pr o priate, ne p hr ol o g y c o ns ultati o n ma y be rec o m me n de d t o facilitate differe ntiati o n of 
re nal pare nc hy m al disease, pre-re nal az ote mia, a n d p ost-re nal o bstr ucti o n. All c o nfir me d 
cases of cli nicall y rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d p ote ntial cases 
of DI KI if n o ot her reas o n f or t he ki d ne y f u ncti o n a b n or malities has bee n f o u n d.
7. 1. 2. E C G C h a n ges
A partici pa nt w h o meets eit her b ullete d criteri o n base d o n t he a vera ge of tri p licate E C G 
rea di n gs will be wit h dra w n fr o m t he st u dy i nter ve nti o n. 

Q Tc F > 5 0 0 ms.

C ha n ge fr o m baseli ne: Q Tc F > 6 0 ms a n d Q Tc F > 4 5 0 ms.
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q Tc F after e nr oll me nt), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d. T his re vie w of t he E C G pri nte d at t he ti me of c ollecti o n m ust be d oc u me nte d. A n y 
ne w cli n ically rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
7. 1. 3. C O VI D - 1 9
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n A E or S A E (as 
a p pr o priate) a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. St u d y  treat me nt s h o ul d c o nti n ue 
u nless t he i n vesti gat or/treati n g p hys icia n is c o ncer ne d a b o ut t he safety of t he partici pa nt, i n 
w hic h case te m p orar y  or per ma ne nt disc o nti n uati o n ma y be re q uire d.
It is rec o m me n de d t hat t he i n vesti gat or disc uss te m p orar y or per ma ne nt disc o nti n uati o n of 
st u d y i nter venti o n wit h t he st u d y  me dical m o nit or. 
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al F r o m t he St u d y
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at t heir o w n re q uest . Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y  pr oce d ures,

L ost t o f oll o w - u p,

Deat h,
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

St u d y  ter mi nate d b y t he s p o ns or,

I n vesti gat or’s decisi o n,

Pre g na nc y .
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d . See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y . Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
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 p r oce d ures. T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecifically wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h t he m or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his i nf or mati o n. 
Partici pa nt s s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt 
fr o m f ut ure f oll o w-u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y  t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y fr o m 
f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures a n d/ or p osttreat me nt st u d y 
f oll o w-u p, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat vital stat us ( w het her 
t he partici pa nt is ali ve or dea d) is bei n g meas ure d, p u blicl y a vaila ble i nf or mati o n s h o ul d be 
use d t o deter mi ne vital stat us o nl y  as a p pr o priatel y directe d i n acc or da nce wit h l ocal la w.
7. 3. L ost t o F oll o w -U p
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if t he partici pa nt re peate dl y fails t o ret ur n 
f or sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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. C o 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 a n d B aseli ne Pr oce d ures
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures.  
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol w ai vers or 
e xe m pti o ns are n ot all o we d.
Safet y  iss ues s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n occ urre nce or 
a ware ness t o deter mi ne w het her t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y  
i nter ve nti o n.
A d here nce t o t he st u d y desi g n re q uire m e 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
to 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.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u mst a 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 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 orme d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
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 R , B P , a n d R R) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g , st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nt s i n t his st u d y is a p pr o xi matel y 
2 5 5 m L . T he act ual c ollecti on 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 
Pri or a n d C o nc o mita nt T hera p y secti o ns of t he pr ot oc ol.
8. 2. Effic ac y Assess me nts
Efficac y  para meters are n ot e val uate d i n t his st u d y. 
8. 3. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d safet y
meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess an 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 n d C V s yste 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 pr actiti o ner as acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets s o t hat o nl y 
li g ht cl ot hi n g re mai ns. 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. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 . Partici pa nt s s h o ul d be 
i nstr ucte d n ot t o s pea k d uri n g meas ure me nts.
T he sa me pr o perl y size d a n d cali brate d B P c uff will be use d t o meas ure B P eac h ti me. T he 
use of a n a ut o mate d de vice f or meas uri n g B P a n d P R is acce pta ble; h o we ver, w he n d o ne 
ma n uall y , P R will be meas ure d i n t he brac hial/ra dial arter y  f or at least 3 0 sec o n ds. W he n t he 
ti mi n g of t hese meas ure me nts c oi nci des wit h a bl o o d c ollecti o n, B P a n d P R 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 R will be per mitte d, 
as necessar y, t o e ns ure a p pr o priate c ollecti o n of safety 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 ocesse s i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 2. 2. Res pir at or y R ate
Res pira t or y rate will be meas ure d after a p pr o xi matel y 5 mi n utes of rest i n a s u pi ne p ositi o n 
b y  o bser vi n g a n d c o u nti n g t he res pirati o ns of t he partici pa nt f or 3 0 sec o n ds a n d m ulti plyi n g
b y  2. W he n B P is t o be ta ke n at t he sa me ti me, res pirati o n meas ure me nt will be d o ne d uri n g
t he 5 mi n utes of rest a n d bef ore B P meas ure me nt.
8. 3. 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
p r 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
i nter val, Q T i nter val, Q TcF, a n d Q R S i nter val. 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 uietl y  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 nts, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o baseli ne meas ure me nts. 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 by ≥6 0 msec fr o m t he baseli ne a n d is > 4 5 0 msec ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 msec f or a ny s c 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 val ues fr o m t hese re peated E C Gs re mai n a b o ve t he 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
t hres h ol d val ue, t he n a si n gle E C G m ust be re peate d at least h o urly u ntil Q Tc val ues fr o m 
2 s uccessi ve E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat meas ure me nt.
If a) a p ost d ose Q Tc F i nter val re mai ns ≥6 0 msec fr o m t he baseli ne a n d is > 4 5 0 msec; or b) 
a n a bs ol ute Q T val ue is ≥5 0 0 msec f or a n y s c 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 i nter vals 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 ous 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 Tc F i nter vals 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 pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y. It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne-rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o vi der’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 8 .
8. 3. 4. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A . 
U nsc he d ule d cli nical la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.  
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y si g nifica nt c ha n ges occ urri n g d uri n g t he st u d y  i n t he A E secti o n of t he C R F. 
Cli nicall y  si g nifica nt a b n or mal la b orat or y test fi n di n gs are t h ose t hat are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt’s c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d 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 mo 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 s ma y u n der g o ra n d o m uri ne dr u g testi n g at t he discreti o n of t he i n vesti gat or.
Dr u g testi n g c o n d ucte d pri or t o d osi n g m ust be ne gati ve f or partici pa nt s t o recei ve st u d y 
i nter ve nti o n.
8. 3. 5. C O VI D - 1 9 Specific A ssess me nts
Partici pa nts will be teste d f or C O VI D -1 9 i nfecti o n b y  P C R pri or t o bei n g a d mitte d t o t he 
cli nic f or c o nfi ne me nt a n d a s u bse q ue nt C O VI D -1 9 test will be perf or me d if t he y  de vel o p 
C O VI D -1 9- li ke sy m pt o ms. A d diti o nal testi n g ma y  be re q uire d b y l ocal re g ulati o ns or b y t he 
PI .
8. 3. 6. Pre g n a nc y Testi n g
A uri ne or ser u m pre g na nc y test is re q uire d at scree ni n g. F oll o wi n g scree ni n g, p re g na nc y 
tests ma y be uri ne or ser u m tests, a n d m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L. 
Pre g na nc y  tests will be perf or me d i n W O C B P at t he ti mes liste d i n t he S o A . F oll o wi n g a 
ne gati ve pre g na nc y  test res ult at scree ni n g, a p pr o priate c o ntrace pti o n m ust be c o m me nce d 
a n d a sec o n d ne gati ve pre g na nc y  test res ult will be re q uire d at t he baseli ne visit pri or t o 
starti n g t he st u d y i nter ve nti o n. Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c ycle 
is misse d d uri n g t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise 
s us pecte d) a n d at t he e n d of t he st u d y. Pre g na nc y tests ma y als o be re peate d if re q ueste d by 
I RBs/ E C s or if re q uire d b y l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d as ne gati ve 
(e g, a n a m bi g u o us res ult), a ser u m pre g na nc y test is re q uire d. I n s uc h cases, t he partici pa nt 
m ust be e xcl u de d if t he ser u m pre g na nc y  res ult is p ositi ve.
8. 4. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A E s ma y arise fr o m s ym pt o ms or ot her c o m plai nts re p orte d t o t he i n vesti gat or b y  t he 
partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he partici pa nt ’s le gall y 
a ut h orize d re prese ntati ve), or t he y  ma y arise fr o m cli nical fi n di n gs of t he in vesti gat or or 
ot her h ealt hcare pr o vi ders (cli nical si g ns, test res ults, etc).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o assess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 4. 1 , eac h partici pa nt will be 
q uesti o ne d a b o ut t he occ urre nce of A E s i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y Pfizer Safety t o o btai n s pecific f oll o w -u p 
i nf or matio n i n a n e x pe dite d fas hi o n.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g AE s a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore u n der g oi n g a n y st u d y- relate d pr oce d ure a n d/ or recei vi n g st u d y 
i nter ve nti o n), t hr o u g h a n d i ncl u di n g a mi ni m u m of 2 8 cale n dar da ys, e xce pt as i n dicate d 
bel o w , after t he last a d mi nistrati o n of t he st u d y i nter ve nti o n.
F oll o w -u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut t he acti ve c ollecti o n peri o d a n d u ntil t he 
A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or.
W he n a cli nicall y  i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
F or partici pa nts w h o are scree n fail ures, t he acti ve c oll ecti 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 m a ne ntl y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A Es or S A E s after t he 
partici pa nt has c o ncl u de d st u d y partici pati o n. H o we ver, if t he i n vesti gat or lear ns of a ny S A E, 
i ncl u di n g a deat h, at a ny ti me after a partici pa nt has c o ncl u de d st u d y 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 relate d t o t he st u d y  i nter ve nti o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m.
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n pe ri o d as descri be d i n 
S ecti o n 8. 4. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m i m me diatel y u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it s bei n g a vaila ble.
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n S ecti o n 8. 4. 1 , will be rec orde 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 4. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure, occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o vi ders, fa mil y me m bers, a n d ot hers w h o ma y be e x p ose d. A n 
e n vir o n me ntal e x p os ure ma y  i ncl u de E D P, E D B , a n d occ u pati o nal e x p os ure.
A n y  s uc h ex p os ure s t o t he st u d y i nter ve nti o n u n der st u d y  are re p orta ble t o Pfizer Safet y 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
8. 4. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y  i nter ve nti o n
i nse mi nates a fe male part ner.

A fe male n o n partici pa nt is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n 
e x p ose d t o st u d y i nter ve nti o n beca use of e n vir o n me ntal e x p os ure. Bel o w are 
e xa m ples of e n vir o n me ntal E D P :  

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n 
c o ntact .

A male fa mil y me m b er or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n c o ntact t he n i nse mi nates his fe male 
part ner pri or t o or ar o u n d t he ti me of c o nce pti o n .
T he i n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial i nf or mati o n s u b mitte d 
s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y). 

If E D P occ urs i n a participa nt /partici pa nt’s part ner, t he i n vesti gat or m ust re p ort t his 
i nf or mati o n t o Pfizer Safet y  o n t he C T S A E Re p ort F or m a n d a n 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

If E D P occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p o rt F or m a n d E D P S u p ple me ntal 
F or m. Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n 
t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he 
c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file.
F oll o w- u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
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 bl e, 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 nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b o ut pre g na nc y o utc o mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n s h o ul d be re p orted 
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 oss i bl y relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or. F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case-b y -case basis (e g, f oll o w- u p o n 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela 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 partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male n o n partici pa nt is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g 
bee n e x p ose d t o st u d y  i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Me dicati o n err ors are rec or de d a n d re p orte d as f oll o ws:
Rec or de d o n t he 
Me dic ati o n Err or P a ge 
of t he C R F
Rec or de d o n t he 
A d verse E ve nt P a ge 
of t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y  A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y  if ass ociate d wit h a n 
S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y partici pa nt .
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, s uc h me dicati o n err or s occ urri n g t o a st u d y partici pa nt are rec or de d o n t he 
me dicati o n err or pa ge of t he C R F , w hic h is a s pecific versi o n of t he A E pa ge a n d, if 
a p plica ble, a n y ass ociate d seri o us a n d n o nseri o us A E(s) , are rec or de d o n t he A E pa ge of t he 
C R F .
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs .
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4
h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wi t h a n S A E.
8. 5. P h ar m ac o ki netics 
8. 5. 1. Pl as m a f or A n al ysis of P F -0 7 8 1 7 8 8 3
Bl o o d sa m ples of a p pr o xi matel y  4 m L , t o pr o vi de a p pr o xi matel y 1. 5 m L of plas ma , will be 
c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 as s pecifie d i n t he S o A .
Pri or t o ce ntrif u gati o n at t he ti me p oi nt s pecifie d i n t he S o A a 0. 1-m L  p orti o n of t he P K 
bl o o d sa m ple will be ali q u ote d a n d use d t o deter mi ne t he bl o o d t o plas ma rati o of 
P F - 0 7 8 1 7 8 8 3. Ex pl orat or y micr o -sa m pli n g P K bl o o d sa m ples f or t he meas ure me nt of 
P F -0 7 8 1 7 8 8 3 c o nce ntrati o ns will als o be c ollecte d usi n g t he Tass o ® M 2 0 de vice . T otal 
bl o o d v ol u me f or e x pl orat or y  micr osa m pli n g P K will n ot e xcee d 0. 1 m L at eac h ti me p oi nt 
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 borat 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 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 7
1 0 % of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n utes of a 6 0 -mi n ute sa m ple) will 
n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n 
t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa mples m ore t ha n 1 0 h o urs after d ose
a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y  fr o m t he n o mi nal ti me relati ve t o d osi n g will 
n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n 
t he s o urce d oc u me nt a n d t he C R F.
Sa m ples will be use d t o e val uate t he P K of P F -0 7 8 1 7 8 8 3 . Sa m ples c ollecte d f or a nalys es of 
P F -0 7 8 1 7 8 8 3 plas ma c o nce ntrati o n ma y als o be use d t o e val uate safety or efficac y  as pects 
relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y, f or meta b olite i de ntificati o n a n d/ or 
e val uati o n of t he bi oa nal ytical met h o d, or f or ot her i nter nal e x pl orat or y  p ur p oses. T he 
e x pl orat or y res ults ma y n ot be re p orte d i n t he C S R.
Ge netic a nal ys es will n ot be perf or me d o n t hese P K plas ma sa m ples u nless c o nse nt f or t his 
was i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y  will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 will be 
a nal yz e d usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h a p plica ble S O Ps. P ote ntial 
meta b olites ma y  be a nalyze d wit h eit her vali date d or e x pl orat or y met h o ds.
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y  de viati o ns fr o m t he P K sa m ple 
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns 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  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a ny pla n ne d st u d y assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol de viati o n . T he IR B/ E C will be 
i nf or me d of a ny s afet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 5. 2. Uri ne f or A n al ysis of P F - 0 7 8 1 7 8 8 3
Uri ne will be c ollecte d as s pecifie d i n t he S o A . Eac h partici pa nt will e m pty his/ her bla d der 
j ust pri or t o d osi n g. A 5 m L  ali q u ot fr o m t his uri ne b la n k will be la bele d a n d fr oze n . D uri n g 
t he s u bse q ue nt desi g nate d uri ne c ollecti o n i nter val ([ 0- 2 4] h o urs p ost d ose), partici pa nts will 
v oi d A L L uri ne pr o d uce d d uri n g t he desi g nate d c ollecti o n i nter val, i ncl u di n g a f orce d v oi d at 
t he e n d of t he c ollecti o n i nter val, directl y i nt o pre-wei g he d uri ne c ollecti o n c o ntai ner. D uri n g 
t he e ntire c ollecti o n i nter val, t he c o ntai ner(s) s h o ul d be st ore d at 4° C. At t he e n d of eac h 
uri ne c ollecti o n i nter val, all uri ne c ollecte d will be t h or o u g hl y mi xe d, t otal wei g ht of uri ne 
will be deter mi ne d first ( wei g h t he e m pt y c o ntai ner first a n d t he n wei g h t he c o ntai ner at t he 
e n d of t he c ollecti o n) a n d t he n t he v ol u me of uri ne will be calc ulate d b y ass u mi n g s pecific 
gra vit y  of uri ne = 1 a n d rec or de d o n t he C R F. A uri ne ali q u ot of 5 m L  will be wit h dra w n f or 
meas ure me nt of dr u g c o nce ntrati o ns. A d diti o nal details f or c ollecti o n, pr ocessi n g a n d st ora ge 
of uri ne f or a nal ys is of P F-0 7 8 1 7 8 8 3 will be a d de d t o t he la b orat or y  ma n ual a n d pr o vi de d t o 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
t he i n vesti gat or site pri or t o t he start of t he st u d y. Uri ne sa m ples will be a nal yze d f or 
P F -0 7 8 1 7 8 8 3 usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h Pfizer S O Ps, if it is 
deter mi ne d b y t he st u d y t ea m t hat t here is a nee d t o d o s o, base d o n re vie w of plas ma P K 
res ults f or P F-0 7 8 1 7 8 8 3. 
Uri ne sa m ples ma y  be use d f or meta b olite i de ntificati o n a n d/ or e val uati o n of t he 
bi oa nal y tical met h o d, or f or ot her i nter nal e x pl orat or y p ur p oses.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
S pecifie d g e netic a nal ys es are n ot e val uate d i n t his st u d y .
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
A 4- m L  bl o o d sa m ple opti mize d f or D N A is olati o n Pre p D 1 will be c ollecte d acc or di n g t o 
t he S o A , as l ocal re g ulati o ns a n d IR Bs/ E C s all o w.
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n(s). 
Ge nes a n d ot her a nal ytes (e g, pr otei ns, R N A, n o n dr u g meta b olites) ma y  be st u die d usi n g t he 
retai ne d sa m ples. 
See A p pe n di x 5 f or inf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b orat or y ma n ual a n d 
s u p p orti n g d oc u me ntati o n.
8. 7. Bi o m ar kers
Bi o mar kers are n ot e val uate d i n t his st u d y .
8. 8. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y .
8. 9. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n a n d h ealt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d f urt her detaile d i n t he S A P, w hic h will be mai ntai ne d b y  t he s p o ns or. 
T he S A P ma y  m o dif y w hat is o utli ne d i n t he pr ot oc ol w here a p pr o priate; h o we ver, a n y  maj or 
m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot heses
T here are n o statistical h y p ot heses f or t his st u d y .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d
" E nr olle d" mea ns a partici pa nt's, or t heir le gally a ut h orize d 
re prese ntati ve’s, a gree me nt t o partici pate i n a cli nical st u d y 
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
assi g n me nt t o st u d y i nter ve nti o n. 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 olle 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 ny st u d y acti vit y.
Safet y anal ys is set
All partici pa nts e nr olle d a n d w h o ta ke at least 1 d ose of st u d y  
i nter ve nti o n.
P K c o nce ntrati o n set
All partici pa nts w h o ta ke at least 1 d ose of st u d y i nter ve nti o n 
a n d i n w h o m at least 1 c o nce ntrati o n val ue is re p orte d.
P K para meter set
All partici pa nts w h o ta ke at least 1 d ose of st u d y i nter ve nti o n 
a n d i n w h o m at least 1 of t he P K para meters of pri mar y  
i nterest are re p orte 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. P h ar m ac o ki netic A n al yses
9. 3. 1. 1. Deri v ati o n of P h ar m ac o ki netic P ar a meters
P K para meters of P F - 0 78 1 7 8 8 3 will be deri ve d (as data per mit s) 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 bel o w. 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 wi ll be use d i n t he deri vati o n of P K para meters. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 0
T a ble 5.
Pl as m a P F -0 7 8 1 7 8 8 3 P K P ar a meter 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 last
Area u n der t he plas ma c o nce ntrati o n -ti me pr ofile 
fr o m ti me zer o t o t he ti me of  t he last q ua ntifia ble 
c o nce ntrati o n ( C last).
Li near/ L o g tra pez oi dal met h o d.
A U C i nf*
Area u n der t he plas ma c o nce ntrati o n ti me
c ur ve fr o m ti me 0 e xtra p olate d t o
i nfi nite ti me
A U C last + ( C last*/ k el),
w here C last* is t he pre dicte d
plas ma c o nce ntrati o n at t he last
q ua ntifia ble ti me p oi nt fr o m t he
l o g-li near re gressi o n a nal ysis
A U C 1 2
Area u n der t he plas ma c o nce ntrati o n -ti me
pr ofile fr o m ti me zer o t o 1 2 h o urs
Li near/ L o g tra pez oi dal met h o d.
C ma x
Ma xi m u m o bser ve d c o nce ntrati o n
O bser ve d directl y fr o m data
T ma x
Ti m e f or C ma x
O bser ve d directl y fr o m data as ti me of 
first occ urre nce
t½ *
T er m i nal half-life
L o g e( 2)/ kel,
w here k el is t he ter mi nal p hase rate 
c o nsta nt calc ulate d b y a li near 
re gressi o n of t he l o gli near 
c o nce ntrati o n-ti me c ur ve. O nl y t h ose 
data p oi nts j u d ge d t o descri be t he 
ter mi nal l o gli near decli ne will be use d 
i n t he re gressi o n.
C L/ F *
A p pare nt cleara nce
D ose/ A U C i nf
V z/ F *
A p pare nt v ol u me of distri b uti o n
D ose/( A U C i nf • k el)
* If data per mits.
If uri ne sa m ples nee d t o be a nalyz e d ( See Secti o n 8. 5. 2 ), t he f oll o wi n g uri ne P K para meters 
(Ta ble 6 ) will be calc ulate d f or P F-0 7 3 2 1 3 3 2 (as data per mit s):
T a ble 6.
Uri ne P F -0 7 8 1 7 8 8 3 P K p ar a meter defi n iti 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
Ae 2 4
T otal a m o u nt of u nc ha n ge d dr u g 
e xcrete d i n t he uri ne o ver 
2 4 h o urs
S u m of a m o u nt e xcrete d f or eac h 
c ollecti o n peri o d.
Ae 2 4 %
T otal a m o u nt of u nc ha n ge d dr u g 
e xcrete d i n t he uri ne o ver 
2 4 h o urs, e x presse d as perce nt of 
d ose
1 0 0 ×( Ae 2 4/ D ose)
C L R
Re nal cleara nce
Ae 2 4/ A U C2 4
Uri ne P K para meters will be a nal yz e d a n d s u m marize d usi n g descri pti ve statistics .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 3. 2. St atistic al Met h o ds f or P K D at a
T he plas ma c o nce ntrati o ns of P F -0 7 8 1 7 8 8 3 will be liste d a n d descri pti vel y s u m marize d b y 
n o mi nal P K sa m pli n g ti me a n d treat me nt. I n di vi d ual partici pa nt, as well as mea n a n d me dia n 
pr ofiles of t he plas ma c o nce ntrati o n ti me data will be pl otte d b y  treat me nt f or eac h a nal yte 
usi n g act ual (f or i n di vi d ual) a n d n o mi nal (f or mea n a n d me dia n) ti mes res pecti vel y. Mea n 
a n d me dia n pr ofiles wil l be prese nte d o n b ot h li near a n d se mi-l o g scales. B o x a n d w his ker 
pl ots f or A U C last a n d C ma x will be pl otte d b y  treat me nt. If t he data all o ws A U Ci nf will be 
calc ulate d a n d i ncl u de d i n t he a nalys is.
Nat ural l o g tra nsf or me d para meters C ma x a n d A U C i nf (if data per mits, ot her wise A U Clast) of
P F - 0 7 8 1 7 8 8 3 will be a nal yze d usi n g a mi xe d effect m o del wit h treat me nt as fi xe d effect a n d 
partici pa nt as a ra n d o m effect. Esti mates of t he a dj uste d mea n differe nces ( Test -Refere nce) 
a n d c orres p o n di n g 9 0 % CI s will be o btaine d fr o m t he m o del. T he a dj uste d mea n differe nces 
a n d 9 0 % CIs f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of 
a dj uste d ge o metric mea ns ( Test/ Refere nce) a n d 9 0 % CI  f or t he rati os. P F-0 7 8 1 7 8 8 3
a d mi nistere d al o ne will be t he Ref ere nce treat me nt a n d P F-0 7 8 1 7 8 8 3 c o-a d mi nistere d wit h 
itrac o naz ole will be t he Test treat me nt.
A d diti o nal s pecificati o ns a b o ut t he ta bles, listi n gs, a n d fi g ures will be o utli ne d i n t he S A P.
9. 3. 3. Ot her S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t h e safet y p o p ulati o n.
A E s, E C Gs, B P , p ulse rate , R R, a n d safet y la b orat or y data will be re vie we d a n d s u m marize d 
o n a n o n g oi n g basis d uri n g t he st u d y t o e val uate t he safet y of partici pa nt s. A n y cli nical 
la b orat or y, E C G, B P, p ulse rate , or R R a b n or mality of p ote ntial cli nical c o ncer n will be 
descri be d. Safet y data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d 
descri pti vel y, w here a p pr o priate.
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 active 
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 wi ll n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.
9. 3. 4. Ot her A n al yses 
Bi o mar ker data fr o m Retai ne d Researc h Sa m ples ma y  be c ollecte d d uri n g or after t he trial 
a n d retai ne d f or f ut ure a nal yses; t he res ults of s uc h a nalys es are n ot pla n ne d t o be i ncl u de d i n 
t he C S R.
9. 4. I nteri m A n al yses
N o i nteri m a nal ys is will be c o n d ucte d f or t his st u d y.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
9. 5. S a m ple Size Deter mi n ati o n
A sa m ple size of 10 partici pa nts will pr o vi de a de q uate precisi o n t o esti mate t he effects of 
itrac o naz ole o n t he P K of P F -0 7 8 1 7 8 8 3. T he e x pecte d wi dt hs of t he 9 0 % CI s wit h 8 0 % 
c o vera ge pr o ba bilit y are s h o w n i n t he f oll o wi n g ta ble f or a ra n ge of p ossi ble effects. 
P a r a m eter
E sti m ate d Effect 
( 1 0 0 * Test/ Refere nce)
9 0 % CI
CI Wi dt h
A U C i nf
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
8 7 %, 1 1 5 %
1 3 0 %, 1 7 3 %
1 7 3 %, 2 3 1 %
2 1 7 %, 2 8 8 %
2 6 0 %, 3 4 6 %
3 4 7 %, 4 6 1 %
2 9 %
4 3 %
5 7 %
7 1 %
8 6 %
1 1 4 %
A U C last
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
8 8 %, 1 1 4 %
1 3 2 %, 1 7 0 %
1 7 6 %, 2 2 7 %
2 2 0 %, 2 8 4 %
2 6 4 %, 3 4 1 %
3 5 2 %, 4 5 4 %
2 6 %
3 8 %
5 1 %
6 4 %
7 7 %
1 0 2 %
C ma x
1 0 0 %
1 5 0 %
2 0 0 %
2 5 0 %
3 0 0 %
4 0 0 %
7 9 %, 1 2 7 %
1 1 8 %, 1 9 0 %
1 5 8 %, 2 5 4 %
1 9 7 %, 3 1 7 %
2 3 6 %, 3 8 1 %
3 1 5 %, 5 0 8 %
4 8 %
7 2 %
9 6 %
1 2 0 %
1 4 4 %
1 9 3 %
T hese esti mates are base d o n t he ass u m pti o n t hat wit hi n -partici pa nt sta n dar d de viati o ns 
are
 a n d
 f orl n A U Ci nf, l n A U Clast a n d l n Cma x , res pecti vel y, as o btai ne d 
fr o m o n g oi n g cli nical st u d y C 5 0 9 1 0 0 1  i n healt hy partici pa nts.
T o all o w f or dr o p o uts , a p pr o xi matel y 1 2 partici pa nts will be e nr olle d i n or der t o ha ve 1 0 P K 
e val uable partici pa nts. Partici pa nts w h o wit h dra w fr o m t he st u d y f or n o n-safety reas o ns m a y  
be re place 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI
C CI

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 ga t or t o pr otect t he st u d y partici pa nt s a gai nst a ny i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or t he i n vesti gat or’s re prese ntati ve will e x plai n t he nat ure of t he st u d y, 
i ncl u di n g t he ris ks a n d be nefits, t o t he partici pa nt a n d a ns wer all q uesti o ns re gar di n g t he 
st u d y. T he partici pa nt s h o ul d be gi ve n s ufficie nt ti me a n d o p p ort u nit y t o as k q uesti o ns a n d t o 
deci de w het her or n ot t o p artici pate i n t he trial.
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts will be 
re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, 
l ocal re g ulati o ns, I C H g ui deli nes, pri vac y  a n d data pr otecti o n re q uire me nts, w here 
a p plica ble, a n d t he I R B/ E C or st u d y  ce nter.
T he i n vesti gat or m ust e ns ure t hat eac h partici pa nt is f ull y i nf or me d a b o ut t he nat ure a n d 
o bjecti ves of t he st u d y, t he s hari n g of data relate d t o t he st u d y , a n d p ossi ble ris ks ass ociate d 
wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt ’s 
pers o nal data. 
T he partici pa nt m ust be i nf or me d t hat t heir pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m 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 
their 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.
A partici pa nt w h o is rescree ne d is n ot re q uire d t o si g n a n ot her I C D if t he rescree ni n g occ urs 
wit hi n 1 0 da y s fr o m t he pre vi o us IC D si g nat ure date.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 5
1 0. 1. 3. D at a Pr otecti o n
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas 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 wh o partici pate d i n t he st u d y , li n ki n g eac h 
partici pa nt ’s n u merical c o de t o t heir act ual i de ntit y a n d me dical rec or d I D. I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he c li nical st u d y a gree 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, a lterati 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. 4. C o m mittees Str uct ure
1 0. 1. 4. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use a n E-D M C.
1 0. 1. 5. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti 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 or te d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 nclu de s u m mar y  d oc u me nts a n d C S Rs 
i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A P s. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt hs after st u d y  c o m pleti o n. Partici pa n t-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. 6. D at a Q u alit y Ass ur a n ce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 uffi cie nt ti me is de v ote d t o t he pr ocess.
M o nit ori n g details descri bi n g strate g y , i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d 
pr ocesses (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y , s uc h as ris k m a na ge me nt a n d 
m iti gati o n strate gies a n d anal y tical 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 1. 7. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste n ce 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 (P 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 (P C R U) .
T he i n ves ti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce rec or d) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he C R F.
T he s p o ns or or desi g nee will perf or m m o nit ori n g t o c o nfir m t hat data e ntere d i nt o t he C R F 
b y  a ut h orize d site pers o n nel are acc urate, c o m plete, a nd 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. 8. 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:
i ncl u di n g b ut n ot li mite d t o, vital si g ns (e g, B P), safety la b tests (eg, he patic e nz y mes) ,
c hil d beari n g stat us (e g, d oc u me nte d h y sterect o m y) ma y  be perf or me d, w here et hically 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:  
p artici 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 n tifier), 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 sys te m if a vaila ble). 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
T here ma y  be u n pla n ne d sit uati o ns w here t he s p o ns or ma y  re q uest me dical rec or ds (e g, 
s hari n g me dical rec or ds s o t hat t he s p o ns or ca n pr o vi de st u d y-relate d a d vice t o t he 
i n vesti gat or). T he me dical rec or ds s h o ul d be s u b mitte d acc or di n g t o t he pr oce d ure descri be d 
a b o ve.
1 0. 1. 9. S t u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or , i ncl u di n g ( b ut n ot li mite d t o) 
re g ulat or y a ut h ority decisi o n, c ha n ge i n o pi ni o n of t he I R B/ E C, or c ha n ge i n be nefit -ris k 
assess me nt . St u d y  sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d 
cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve bee n c ollecte d a n d a st u 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 healt h a ut h orit ies, t he s p o ns or’s pr oce d ures, or t he I CH G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t h e c o ntract a n d t his pr ot oc ol , t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 1 0. P u blic ati o n P olic y
T he res ults of t his st u d y  ma y be p u blis he d or prese nte d at scie ntific meeti n gs by t he 
i n vesti gat or after p u blicati o n of t he o verall st u d y res ults or 1 ye ar after t he e n d of t he st u d y 
( or st u d y ter mi nati o n), w hic he ver c o mes first. 
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns, 
s uc h as sec o n dar y ma n uscri pts, a n d s u b mits all ma n uscri pts or a bstracts t o t he s p o ns or 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
3 0 da y s bef ore s u b missi o n. T his all o ws t he s p o ns or 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 - or Pfizer-i nter ve nti o n 
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 all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or 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 blicatio 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 s p o ns or will c o m pl y  wit h t he re q uire me nts f or p u blicati o n of t he o verall st u d y res ults 
c o veri n g all i n vesti gat or sites. I n acc or da nce wit h sta n da r d e dit orial a n d et hical practice, t he 
s p o ns or will s u p p ort p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as 
i n di vi d ual site data. In t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y  m ut ual 
a gree me nt.
A ut h ors hi p of p u blicati o ns f or t he o verall st u d y  res ults will be deter mi ne d b y m ut ual 
a gree me nt a n d i n li ne wit h Inter nati o nal C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p 
re q uire me nts. 
If p u blicati o n is a d dresse d i n t he cli nical st u d y a gree me nt, t he p u blicati o n p olic y set out i n 
t his secti o n will n ot a p pl y.
1 0. 1. 1 1. 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 nc y p h o ne n u m ber acti ve 2 4 h o urs/ da y, 7 da ys per wee k.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he partici pa nt a n d t heir i n vesti gat or a n d site staff, a n d bet wee n t he i n vesti gat or a n d 
s p o ns or st u d y tea m. T he E C C is o nl y t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n 
t he researc h st u dy, as a mea ns of reac hi n g t he i n vesti gat or or site staff relate d t o t he care of a 
partici pa nt. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 1
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y, or as deri ve d 
fr o m calc ulate d val ues. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nical la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y iss ues.
T a ble 7.
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
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils ( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
M C V
M C H
M C H C
Urea
Creati ni ne
Ser u m c ystati n C a
e G F R, e Cr Cl b
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T
T otal bilir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
L ocal Di pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y
a n d 
C ult ure c
C O VI D -1 9 testi n g
Uri ne dr u g scree ni n g d
Pre g na nc y Test e
At S cree ni n g o nl y:
F S H f
H B s A g
H Bs A b
H C V A b
HI V
a.
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.
d.
T he m i ni m u m re q uire me nt f or dr u g scree ni n g i ncl u des c ocai ne, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, a n d 
a mp heta mi nes ( ot hers are site - a n d st u d y- s pecific). 
e.
L ocal uri ne testi n g will be sta n dar d f or t he pr ot oc ol u nless ser u m testi n g is re q uire d b y l ocal re g ulat i o n or I R B/ E C. 
See S o A f or c ollecti o n ti mes.
f.
F or c o nfir mati o n of p ost me n o pa usal stat us o nl y i n fe males < 6 0 years ol d a n d n ot usi n g h or m o nal or H R T o nl y.
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 ny 
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 nist rati 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 the C S R . Sa m ples t o be use d f or t his 
p ur p ose will be s hi p pe d t o eit her a Pfizer -a p pr o ve d B B S facilit y or ot her desi g nate d 
la b orat or y a n d retai ne d f or u p t o 1 ye ar f oll o wi n g t he c o m pleti o n of t he st u d y.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w -U p, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or 
n ot c o nsi dere d relate d t o t he st u d y  i nter ve nti o n.

N ote : A n A E ca n t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or 
uri nal y sis) or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y  
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or. A n y 
a b n or mal test res ults t hat meet a n y of t he c o n diti o ns bel o w m ust be rec or de d as 
a n A E:

Is ass ociate d wit h acc o m pa n yi n g sy m pt o ms ;

Re q uire s a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n;

Lea ds t o a c ha n ge i n st u d y  d osi n g ( o utsi de of a n y pr ot oc ol-s pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal 
c o nc o mita nt dr u g treat me nt, or ot her t hera p y.

E xacer bati o n of a c hr o nic or i nter mitte nt pree xisti n g c o n diti o n, i ncl u di n g a n 
i ncrease i n eit her fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o n detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n ,
e ve n t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y .

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y  
i nter ve nti o n or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as 
a n A E or S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble 
s uici dal/self- har mi n g i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of 
se q uelae.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 to 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 ocial 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 E s. 
If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he 
e ve nt is seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
d.
Res ults i n persiste nt or si g nific a nt dis a bilit y/ i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, vo miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle), t hat m a y  i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nit al a n o m al y/ birt h defect
f.
Is a s us pecte d tr a ns missi o n vi a a Pfizer pr o d uct of a n i nfecti o us a ge nt, 
p at h o ge nic or n o n -p at h o ge nic 
T he e ve nt ma y  be s us pecte d fr o m cli nical sy m pt o ms or la b orat or y  fi n di n gs 
i n dicati n g a n i nfecti o n i n a partici pa nt e x p ose d t o a Pfizer pr o d uct. T he ter ms 
“s us pecte d tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d s y n o n y m o us. T hese 
cases are c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y 
p har mac o vi gila nce pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o priate.
g.
Ot her sit u ati o ns:

Me dic al 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 to 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. 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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. Whe 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 E s 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 
there is a n ass ociate d 
S A E) * *
E n vir o n me ntal or 
occ u pati o nal e x p os ure 
t o t he pr o d uct u n der 
st u d y t o a 
n o n partici pa nt ( n ot 
i n v ol vi n g E D P or E D B)
N o ne. E x p os ure t o a st u d y 
n o n- partici pa nt is n ot 
c ollecte d o n t he C R F
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
re p orte d * * *
*
E D P ( wit h or wit h o ut a n ass ociate d S A E): is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort 
F or m  a n d E D P S u p ple me ntal F or m. 
* * E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m, w hic h w o ul d als o i ncl u de 
details of a n y S A E t hat mi g ht be ass ociate d w it h t he E D B. 
* * * E n vir o n me nt al or o cc u p ati o n al e x p os ure: A E s or S A Es ass ociate d wit h occ 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.

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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 7

T he i n vesti gat or will als o c o ns ult t he I B a n d/ or p r o d uct inf or mati o n, f or 
mar kete d pr o d ucts, i n t heir assess me nt.

F or eac h A E or S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat 
t he y ha ve re vie we d t he A E or S A E a n d ha v e pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p o ns or. H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he 
s p o ns or.

T he i n vesti gat or ma y  c ha n ge t heir o pi ni o n of ca usalit y  i n li g ht of f oll o w-u p 
i nf or mati o n a n d se n d an S A E f oll o w -u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or 
re p orti n g p ur p oses, as defi ne d b y t he s p o ns or. I n a d diti o n, if t he i n vesti gat or 
deter mi nes t hat a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or 
m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort 
s uc h a n assess me nt i n t he de dicate d secti on of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
F oll o w - Up of A E s a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of 
s u p ple me ntal meas ure me nts a n d/ or e val uati o ns, as me dicall y i n dicate d or as 
re q ueste d by t he s p o ns or, t o el uci date t he nat ure a n d/ or ca usality of t he A E or 
S A E as f ull y  as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt hcare pr o vi ders .

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs , i ncl u di n g hist o pat h ol o g y.

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  s u b mitte d 
d oc u me nts .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 8

T 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 Es
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 ds t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y .

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, a n alter nati ve met h o d s h o ul d 
be use d, e g, sec ure d ( Tra ns p ort L a yer Sec urit y) or pass w or d-pr otecte d e mail. I f 
n o ne of t hese met h o ds ca n be use d, n otificati o n b y tele p h o ne is acce pta ble wit h a 
c o p y of t he C T S A E Re p ort F or m se nt by o ver ni g ht mail or c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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. 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 6 0 d a y s after t he last d ose of st u d y i nter ve nti o n, w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safety ris k of t he st u d y 
i nter ve nti o n(s): 

Refrai n fr o m d o nati n g s per m .
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse as t heir preferre d a n d us ual lifest y le 
(a bsti ne nt o n a l o n g-ter m a n d persiste nt basis) a n d a gree t o re mai n a bsti ne nt.
O R

M ust a gree t o use c o ntrace pti o n/ barrier as detaile d bel o w:

A gree t o use a male c o n d o m a n d s h o ul d als o be a d vise d of t he be nefit f or a 
fe male part ner t o use a hi g hly effecti ve met h o d of c o ntrace pti o n , as a c o n d o m 
ma y  brea k or lea k, w he n ha vi n g se x ual i nterc o urse wit h a W O C B P
w h o is n ot 
c urre ntl y pre g na nt.

I n a d diti o n t o male c o n d o m use, a hi g hly effecti ve met h o d of c o ntrace pti o n ma y be 
c o nsi dere d i n W O C B P part ners of male partici pa nts (refer t o t he list of hi g hl y 
effecti ve met h o ds bel o w i n Secti o n 1 0. 4. 4 ).
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
T he criteria bel o w are part of I ncl usi o n Criteri o n 1 ( A ge a n d Se x; Secti o n 5. 1 ) a n d s pecif y 
t he re pr o d ucti ve re q uire me nts f or i ncl u di n g fe male partici pa nts.  Refer t o Secti o n 1 0. 4. 4 f or a 
c o m plete list of c o ntrace pti ve met h o ds per mitte d i n t he st u d y . 
A fe male partici pa nt is eli gi ble t o partici pate if s he (a) is n ot pre g na nt or breastfee di n g; a n d 
( b) a grees n ot t o d o nate e g gs ( o va, o oc ytes) f or t he p ur p ose of re pr o d ucti o n; a n d (c) at least 1
of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d a grees t o use a c o ntrace pti ve met h o d t hat is hi g hl y  effecti ve (fail ure 
rate of < 1 % per year) wit h l o w user de pe n de nc y d uri n g t he i nter ve nti o n peri o d a n d 
f or at least 6 0 d a y s after t he last d ose of st u d y i nter ve nti o n, w hic h c orres p o n ds t o t he 
ti me nee de d t o eli mi nate a n y re pr o d ucti ve safety ris k of t he st u d y i nter ve nti o n(s). T he 
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n 
relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
O R

Is a W O C B P a n d a grees t o use a hi g hl y effecti ve (fail ure rate of < 1 % per year) user -
de pe n de nt met h o d of c o ntrace pti o n d uri n g t he i nter ve nti o n peri o d a n d f or at least 
6 0 da y s after t he last d ose of st u d y i nter ve nti o n, w hic h c orres p o n ds t o t he ti me 
nee de d t o eli mi nate a n y re pr o d ucti ve safety ris k of t he st u d y i nter ve nti o n(s). I n 
a d diti o n t o her use of t he hi g hl y effecti ve met h o d a b o ve, s he a grees t o c o nc urre ntl y
use a n effecti ve barrier met h o d. T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of 
t he c o ntrace pti ve met h o d i n relati o ns hi p t o t he first d ose of st u d y  i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d 
pre g n a nc y. 
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea or oli g o me n orr hea ) a n d a me nstr ual c ycle ca n n ot be 
c o nfir me d bef ore t he first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a me dical ca use ot her t ha n t he a b o ve
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site pers 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.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
2.
P ost me n o pa usal fe male .

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A h i g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars ol d a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A f e male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o 
use o ne of t he hi g hl y effecti ve n o nestr o ge n h or m o nal c o ntrace pti o n met h o ds 
if s he wis h es t o c o nti n ue her H R T d uri n g t he st u d y . Ot her wise, s he m ust 
disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  
e nr oll me nt.
1 0. 4. 4. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat H a ve L o w User De pe n de nc y 
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 nfir me d. If n ot, a n a d diti o nal hi g hl y effecti ve met h o d of c o ntrace pti o n 
s h o ul d be use d. T he s per mat o ge nesis c ycle is a p pr o xi matel y 9 0 da ys.
Hi g hl y Effecti ve Met h o ds T hat A re User D e pe n de nt 
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 + barrier *

I ntra va gi nal + barrier*
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

Tra ns der mal + barrier *
7.
Pr o gest o ge n -o nl y h or m o ne c o ntrace pti o n ass ociate d wi t h i n hi biti o n of o v ulati o n:

Oral + barrier *

I njecta ble + barrier *
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 s t u d y i nter ve nti o n.  T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual lifestyl e of t he 
partici pa nt
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o ns 6 or 7 f or t he st u d y 
i ncl u de a ny of t he f oll o wi n g:

Male or fe male c o n d o m wit h or wit h o ut s per mici de;

Cer vical ca p, dia p hra g m, or s p o n ge wit h s per mici de;

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m, or s p o n ge 
wit h s per mici de ( d o u ble -barrier met h o ds).
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 4
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o ns a n d F oll o w- U p Assess me nts
P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y b ut a da pt 
are ter me d “a da pt ors.” I n s o me partici pa nt s, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me. T hese partici pa nt s fail t o a da pt a n d t heref ore are 
“s usce pti ble” t o pr o gressi ve a n d seri o us li ver i nj ur y, c o m m o nly referre d t o as DI LI. 
Partici pa nt s w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 × U L N s h o ul d be m o nit ore d 
m ore fre q ue ntl y  t o deter mi ne if t he y are “a da pt ors” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T a n d/ or A L T prece de T bili ele vati o ns 
( > 2 × U L N) b y  se veral da ys or wee ks. T he i ncrease i n T b ili t ypicall y  occ urs w hile 
A S T/ A L T is/are still ele vate d a b o ve 3 × U L N (ie, A S T/ A L T a n d T b ili val ues will be 
ele vate d wit hi n t he sa me la b orat or y sa m ple). I n rare i nsta nces, b y t he ti me T b ili ele vati o ns 
are detecte d, A S T/ A L T val ues mi g ht ha ve decrease d. T his occ urre nce is sti ll re gar de d as a 
p ote ntial DI LI. T heref ore, a b n or mal ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T b ili 
t hat meet t he criteria o utli ne d bel o w are c o nsi dere d p ote ntial DI LI (assesse d per H y’s la w 
criteria) cases a n d s h o ul d al wa ys be c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all 
ot her p ossi ble ca uses of li ver i nj ur y  ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt ’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nt s w ho 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 nor 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 L T a n d T b ili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 y s is i n dicate d:
A D U L T S: C urre ntl y, 2 0 2 1 C K D -E PI  e G F R e q uati o ns ( Screat o nl y-base d a n d c o m bi ne d 
Screat pl us Sc y s-base d) are vali d f or use i n a d ults o nl y . At baseli ne Screat a n d Sc ys val ues 
are nee de d t o calc ulate 2 0 2 1 C K D-E PI  e G F R b y Screat o nly- base d e q uati o n (see 
Ta ble 1 0. 7. 2. 1.) a n d b y 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 m 2)[1 4 ]
2 0 2 1 C K D -
E PI            
Scre 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 × ( Screat / 0. 7)- 0. 2 4 1  ×  ( 0. 9 9 3 8) A ge
Fe male
if > 0. 7
N A
e G F R = 1 4 3 × (Screat / 0. 7)- 1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
Male
if ≤ 0. 9
N A
e G F R = 1 4 2 × (Screat / 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 × (Screat / 0. 9)- 1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI           
Scre at -Sc ys 
C o m bi ne d
Scre 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 × (Screat / 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 × (Screat / 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 × (Screat / 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 × (Screat / 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 × (Screat / 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 × (Screat / 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 × (Screat / 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 × (Screat / 0. 9)- 0. 5 4 4  ×   ( Sc ys/ 0. 8)- 0. 7 7 8  ×
( 0. 9 9 6 1)A ge
I n ker L A et al. N E n gl J Me d. 2 0 2 1; 3 8 5: 1 7 3 7- 4 9.
1 0. 7. 3. A d verse E ve nt Gr a di n g f or Ki d ne y S afet y L a b or at or y A b n or m alities
A E gra di n g f or decli ne i n ki d ne y  f u ncti o n (ie, e G F R or e Cr Cl) will be acc or di n g t o Ki d ne y  
Disease: I m pr o vi n g Gl o bal O utc o mes ( K DI G O) criteria f or b ot h pe diatric a n d a d ult 
partici pa nts .
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
K DI G O criteri a 
gr a de ( G)
St u d y 
P o p ul ati o n
G 1
G 2  
G 3  
G 4  
G 5
Decre ase d Ki d ne y 
F u ncti o n d ue t o 
eit her Ac ute or 
C hr o nic Ki d ne y 
I nj ur y 
A d ult 
partici pa nts
e G F R 
( mL/ mi n/ 1. 7 3 m²)
≥9 0 
≥6 0 t o 8 9
3 0 t o 5 9 
1 5 t o 2 9
< 1 5
K DI G O al b u mi n uri a ( A) 
criteri a
A 1
A 2
A 3
Al b u mi n -t o-cre ati ni ne 
r ati o ( A C R)
< 3 0 m g/ g
O R     
< 3 m g/ m m ol 
3 0 t o 3 0 0 m g/ g
O R 
3 t o 3 0 m g/ m m ol
> 3 0 0 m g/ g 
O R 
> 3 0 m g/ m m ol
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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

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’ durati o n, i ncl u di n g i di o ve ntric ular r h y t h m (H R
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m [s uc h as
torsa des de p oi ntes ]).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d- de gree) h eart b l oc k.
E C G Fi n di n gs T h at Q u alif y as S A Es

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n .

S ustai ne d v e ntric ular ta c h yarr h yt h mias ( > 3 0-sec o n ds d urati o n).

Sec o n d - or t hir d -de gree A V bl oc k re q uiri n g pace ma ker place me nt .

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n .

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he maj or e ve nts of p ote ntial cli nical c o ncer n liste d a b o ve are rec o m me n de d as “alerts” or n otificati o ns 
fr o m t he c ore E C G la borat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be c o nsi dere d as all-
i ncl usi ve of w hat is t o rep orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
1 0. 9. A p pe n di x 9: Dr u g Pr o d uct Acce pt a bilit y Q uesti o n n aire
Str o n gl y A gree
A gree
Neit her A gree 
n or Disa gree
Disa gree
Str o n gl y 
Disa gree
1.
T he s urface 
of t he ta blets 
l o o ke d 
r o u g h ( n ot 
s mo ot h)
1
2
3
4
5
2.
T he ta blets 
ha d a n o d d 
s ha pe ( n ot 
r o u n d, o val, 
or ca ps ule -
s ha pe d)
1
2
3
4
5
3.
T he c ol or of 
t he ta blets 
wa s n ot 
attracti ve
1
2
3
4
5
4.
T he ta blets 
felt c hal k y 
or r o u g h i n 
m y m o ut h
1
2
3
4
5
5.
T he ta blets 
st uc k t o t he 
i nsi de of m y 
m o ut h
1
2
3
4
5
6.
T he ta blets 
felt wa x y i n 
m y m o ut h
1
2
3
4
5
7.
T he ta blets 
be ga n t o 
diss ol ve i n 
m y m o ut h 
bef ore I 
s wall o we d 
t he m
1
2
3
4
5
8.
T he ta blets 
taste d bitter
1
2
3
4
5
9.
T he ta blets 
ha d a s mell
1
2
3
4
5
1 0. W he n I t o o k 
t he ta blets, I 
ha d a 
b ur ni n g 
se nsati o n i n 
m y m o ut h or 
o n m y 
t o n g ue
1
2
3
4
5
1 1. W he n I t o o k 
t he ta blets, I 
ha d a 
b ur ni n g 
1
2
3
4
5
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
Str o n gl y A gree
A gree
Neit her A gree 
n or Disa gree
Disa gree
Str o n gl y 
Disa gree
se nsati o n i n 
m y t hr oat
1 2. T he ta blets 
were t o o bi g 
t o s wall o w
1
2
3
4
5
1 3. T he ta blets 
were 
diffic ult t o 
s wall o w
1
2
3
4
5
1 4. O verall, 
t hese ta blets 
were 
diffic ult t o 
ta ke
1
2
3
4
5
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
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 -B P a p p
a pical t o bas olateral ap pare nt per mea bilit y  c oefficie nt
A 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verity sta n dar dizati o n)
A bs
a bs ol ute
A D L
acti vit y/ acti vities of d ail y li vi n g
A E
a d verse e ve nt
Ae
c u m ulati ve t otal a m o u nt of dr u g rec o vere d u nc ha n ge d i n t he uri ne, 
fr o m ti me 0 t o i nfi nit y
Ae 2 4
c u m ulati ve t otal a m o u nt of dr u g rec o vere d u nc ha n ge d i n t he uri ne, 
fr o m ti me 0 t o 2 4 h o urs
Ae 2 4 %
c u m ulati ve t otal a m o u nt of dr u g rec o vere d u nc ha n ge d i n t he uri ne, 
fr o m ti me 0 t o 2 4 h o urs, e x presse d as perce nt of d ose
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A R D S
ac ute res pirat or y distress s yn dr o me
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c o nce ntrati o n-ti me c ur ve
A U C 1 2
area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o t he 
ti me 1 2 h o urs
A U C 2 4
area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o t he 
ti me 2 4 h o urs
A U C i nf
area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m ti me 0
e xtra p olate d t o i nfi nite ti me
A U C last
area u n der t he plas ma c o nce ntrati o n ti me c ur ve fr o m ti me 0 t o t he 
ti me of t he last q ua ntifia ble c o nce ntrati o n
A 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 R P
breast ca ncer resista nce pr otei n
BI D
t wice a da y
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 F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
c hr o nic ki d ne y disease e pi de mi ol o g y
C L
cleara nce
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
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 O 2
car b o n di o xi de ( bicar b o nate)
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C S R
C li nical S t u d y R e p ort
C T
cli nical trial
C TI S
Cli nical Trial I nf or mati o n S y ste m
C T M S
cli nical trial ma na ge me nt s yste m
C V
cardi o vasc ular
C Y P
c yt oc hr o me P 4 5 0
D C T
data c ollecti o n t o ol
D DI
dr u g -dr u g i nteracti o n 
DI CI
dr u g -i n d uce d creati ni ne i ncrease
DI KI
dr u g -i n d uce d ki d ne y i nj ur y
DI LI
dr u g -i n d uce d li ver i nj ur y
E C
et hics c o m mittee
E C C
emer ge nc y  c o ntact car d
E C G
electr ocar di o gra m or electr ocar di o gra p h y
E U A
E mer ge nc y  Use A ut h orizati o n
e Cr Cl
esti mate d creati ni ne cleara nce
e C R F
electr o nic case re p ort f or m
E D B
e x p os ure d uri n g breastfee di n g
E -D M C
E xter nal Data M o nit ori n g C o m mittee
E D P
e x p os ure d uri n g pre g na nc y
e G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
E O T
en d of treat me nt
e S A E
electr o nic seri o us a d verse e ve nt
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 D A
F o o d a n d Dr u g A d mi nistrati o n
F S H
f ollicle-sti m ulati n g h or m o ne
fu ,h u ma n
free fracti o n i n h u ma ns
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
H Bc A b
he patitis B c ore a nti b o d y
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C o V -2 2 9 E
H u ma n c or o na vir us 2 2 9 E
H C V
he patitis C vir us
H C V A b
he patitis C a nti b o d y
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
In vesti gat or’s B r oc h ure
I C5 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 D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal p r o d uct
I ND
In vesti gati o nal N e w D r 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 PM
i n vesti gati o nal pr o d uct ma n ual
I RB
Instit uti o nal R e vie w B oar d
I V
I ntra ve n o us(ly)
K
Pr o p orti o nalit y  c o nsta nt f or Be dsi de a n d M o difie d Sc h wartz 
E q uati o ns ( ki d ne y  f u ncti o n)
K i
i n hi biti o n c o nsta nt
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
L B B B
left b u n dle bra nc h bl oc k
L F T
li ver f u ncti o n test
m A b
m o n ocl o nal a nti b o d y
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M D R
m e dical d e vice re g ulati o n
M E
Meta b olis m a n d E xcreti o n
M E R S -C o V
Mi d dle East Res pirat or y  S yn dr o me C or o na vir us
M
pr o
mai n pr otease
M QI
me dicall y  q ualifie d i n di vi d ual
M T D
ma xi m u m t olerate d d ose
N A
n ot a p plica ble
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o -o bser ve d -a d verse-effect le vel
O A T P
o r ga nic a ni o n tra ns p orti n g p oly pe pti des
O C T
or ga nic cati o n tra ns p orter
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
P A C L
pr ot oc ol a d mi nistrati ve c ha n ge letter
P -g p
p -gl yc o pr otei n
P B P K
p h y si ol o gically base d p har mac o ki netic m o deli n g
P C R U
Pfizer C li nical R esearc h U nit
P D
p har mac o d y n a mic(s)
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic(s)
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 T H
parat h or m o ne
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q D
o nce a da y
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
R R
res pirat or y rate
S A D
si n gle asce n di n g d ose
S A E
seri o us a d verse e ve nt
S A P
S tatistical A nal y sis P la n
S A R S -C o V -1
Se vere Ac ute Res pirat or y S y n dr o me C or o na vir us 1
S A R S -C o V -2
Se vere Ac ute Res pirat or y S y n dr o me C or o na vir us 2
Screat
ser u m creati ni ne
Sc y s
ser u m c ystati n C
S D
si n gle d ose
S o A
sc he d ule of acti vities
S O P
sta n dar d o perati n g pr oce d ure
S R S D
S i n gle R efere nce S afet y D oc u me nt
S U S A R
S us pecte d U ne x pecte d S eri o us A d verse R eacti o n
t½
ter mi nal half life
T b ili
t otal bilir u bi n
T E A E
treat me nt-e mer ge nt a d verse e ve nts
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me f or Cma x
T O C
ta ble of c o nte nts
U K
U nite d Ki n g d o m
U L N
u p per li mit of n or mal
U S
U nite d States
U S PI
U nite d States Prescri bi n g I nf or mati o n
U TI
uri nar y  tract i nfecti o n
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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
A b bre vi ati o n
Ter m
V z/ F
a p pare nt v ol u me of distri b uti o n
W B C
w hite bl o o d cell
W H O
W orl d Healt h Or ga nizati o n
W O C B P
w o ma n / w o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)
C CI

P F -0 7 8 1 7 8 8 3
Pr ot oc ol C 5 0 9 1 0 0 8
Pr ot oc ol A me n d me nt 1 , 1 9 A pril 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical 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 1. R E F E R E N C E S
1.
W H O Sit uati o n Re p ort 5 1. 1 1 Marc h 2 0 2 0. A vaila ble fr o m: 
htt ps:// w w w. w h o.i nt/e mer ge ncies/ diseases/ n o vel -c or o na vir us -2 0 1 9/sit uati o n -re p orts. 
Accesse d: 2 9 Marc h 2 0 2 0.
2.  
W u Z, Mc G o o ga n J. C haracteristics of a n d i m p orta nt less o ns fr o m t he c or o na vir us 
disease 2 0 1 9 ( C O VI D -1 9) o ut brea k i n C hi na: s u m mar y  of a re p ort of 7 2, 3 1 4 cases 
fr o m t he C hi nese Ce nter f or Disease C o ntr ol a n d Pre ve nti o n. J A M A 
2 0 2 0; 3 2 3( 1 3): 1 2 3 9 - 4 2.
3. 
Ric har ds o n S, Hirsc h J, Narasi m ha n M, et al. Prese nti n g c haracteristics, 
c o m or bi dities, a n d o utc o mes a m o n g 5 7 0 0 patie nts h os pitalize d wit h C O VI D -1 9 i n t he 
Ne w Y or k Cit y area. J A M A. 2 0 2 0; 3 2 3( 2 0): 2 0 5 2 - 9.
4.
D oc hert y A, Harris o n E, Gree n C, et al. Feat ures of 2 0 -1 3 3 U K patie nts i n h os pital 
wit h c o vi d- 1 9 usi n g t he I S A RI C W H O Cli nical C haracterisati o n Pr ot oc ol: 
pr os pecti ve o bser vati o nal c o h ort st u d y . B MJ. 2 0 2 0; 3 6 9: 1-1 2: m 1 9 8 5.
5.
Wa n g D, H u B, H u C, et al. Cli nical c haracteristics of 1 3 8 h os pitalize d patie nts wit h 
2 0 1 9 n o vel c or o na vir us -i nfecte d p ne u m o nia i n W u ha n, C hi na. J A M A. 
2 0 2 0; 3 2 3( 1 1): 1 0 6 1 - 9.
6.
Pei G, Z ha n g Z, Pe n g J, et al. Re nal I n v ol ve me nt a n d Earl y Pr o g n osis i n Patie nts wit h 
C O VI D -1 9 P ne u m o nia. J A m S oc Ne p hr ol. 2 0 2 0; 3 1( 6): 1 1 5 7 - 6 5.
7.
N o p p S, M oi k F, Jil ma B, et al. Ris k of ve n o us t hr o m b oe m b olis m i n patie nts wit h 
C O VI D - 1 9: A sys te matic re vie w a n d meta-a nal ys is. Res Pract T hr o m b Hae m ost. 
2 0 2 0; 4( 7): 1 1 7 8 - 9 1.
8.
Ce nters f or Me dicare & Me dicai d Ser vices. C O VI D -1 9 M o n ocl o nal A nti b o dies. 
A vaila ble fr o m: htt ps:// w w w.c ms. g o v/ m o n ocl o nal . U p date d 1 0 A u g 2 0 2 2. Accesse d: 
0 6 Se p 2 0 2 2.
9.
Nati o nal I nstit utes of Healt h. C O VI D -1 9 Treat me nt G ui deli nes. C or o na vir us Disease 
2 0 1 9 ( C O VI D -1 9) Treat me nt G ui deli nes. A vaila ble at 
htt ps:// w w w.c o vi d 1 9treat me nt g ui deli nes. ni h. g o v/ . U p date d: 1 8 A u g 2 0 2 2. Accesse d: 
1 1 A u g 2 0 2 2.
1 0. 
S P O R A N O X ® (itrac o naz ole) Oral S ol uti o n. U S Prescri bi n g I nf or mati o n ( U S PI ). 
Ja nsse n P har mace uticals, Inc. Tit us ville, NJ 0 8 5 6 0, U S A.
1 1. 
Is o herra ne n N, K u nze K, Alle n K, et al. R ole of itrac o naz ole meta b olites i n C Y P 3 A 4 
i n hi biti o n. Dr u g Meta b olis m a n d Dis p ositi o n. 2 0 0 4 Oct 1; 3 2( 1 0): 1 1 2 1- 3 1.
1 2.
Bar o ne J, K o h J, Bier ma n R, et al. F o o d i nteracti o n a n d stea dy- state p har mac o ki netics 
of itrac o naz ole ca ps ules i n healt h y  male v ol u nteers. A nti micr o b A ge nts C he m ot her. 
1 9 9 3; 3 7( 4): 7 7 8 – 8 4.
1 3.
Li u L, Bell o A, Dresser M, et al. Best practices f or t he use of itrac o naz ole as a 
re place me nt f or ket oc o naz ole i n dr u g – dr u g i nteracti o n st u dies. T he J o ur nal of 
Cli nical P har mac ol o g y . 2 0 1 6 Fe b; 5 6( 2): 1 4 3-5 1.
1 4.
I n ker L, E nea nya N, C ores h J, et al. Ne w Creati ni ne - a n d C ys tati n C-Base d E q uati o ns 
t o Esti mate G F R wit h o ut Race. N E n gl J Me d. 2 0 2 1; 3 8 5( 1 9): 1 7 3 7- 4 9.
0 9 0 1 7 7 e 1 a 0 6 0 b 8 8 2\ 0. 1\ Dr aft\ V er si o n e d O n: 0 8- A pr- 2 0 2 4 0 7: 3 9 ( G M T)

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