Conditions: Healthy
Keywords: COVID-19
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: yes

Brief summary:
The purpose of this study is to learn how Itraconazole affects the blood level of PF-07817883 in Healthy Adults.

This study is seeking participants who are:

* male and female aged 18 to 65 years old,
* overtly healthy. This can be determined my medical evaluation, medical history, lab tests etc.

This study will consist of 2 parts, Period 1 and Period 2.

Period 1: participants will take PF-07817883 one time by mouth at the study clinic.

Period 2: participants will take PF-07817883 one time by mouth at the study clinic. They will also take daily itraconazole by mouth for 7 days.

Participants will stay at the study clinic for 2 weeks in total. The study doctors will collect blood and urine samples from everyone. The study doctors will check participants' reactions to the study medicine for safety measures. There is a follow-up call at 28 to 35 days from the last dose of PF-07817883.

Itraconazole is an approved medicine. It is also a metabolism inhibitor. When taken with some medicines, it affects the actual level of these medicines in the body. This study will compare blood levels of PF-07817883 given with and without Itraconazole. This will help decide safety and right amount for PF-07817883 when given with metabolism inhibitors.

Detailed description:
This is a Phase 1, open-label, 2-period, fixed sequence study to estimate the effect of itraconazole, a strong CYP3A4 inhibitor, on the plasma PK of PF-07817883 in healthy adults. The study will consist of 2 treatments: a single oral dose of PF-07817883 alone and a single oral dose of PF-07817883 in combination with multiple oral doses of itraconazole. The PK and safety will be assessed and compared for single dose of PF-07817883 in period 1 and period 2.

Arms:
arm 1: The treatment arm includes a single dose of PF-07817883 (Period 1 Day 1) arm 2: This treatment arm includes 7-day dosing of itraconazole with a single dose of PF-07817883 Co-administered on Day 4 (Period 2 Day 4)

Interventions: intervention 1: PF-07817883 intervention 2: Itraconazole
Intervention descriptions: intervention 1: Single oral dose (period 1) or co-administered with itraconazole (period 2) intervention 2: Interacting drug which will be given for 7 days in period 2

Protocol document:
Prot_000.pdf: 
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

SAP_001.pdf: 
Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 1 of 21
Protocol C5091008
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
Statistical Analysis Plan 
(SAP)
Version:
1
Date:
30 May 2023
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 2 of 21
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Modifications to the Analysis Plan Described in the Protocol..................................5
2.2. Study Objectives, Endpoints, and Estimands............................................................5
2.3. Study Design .............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7
3.1. Primary Endpoints.....................................................................................................7
3.2. Secondary Endpoints.................................................................................................8
3.3. Other Endpoints.........................................................................................................8
3.3.1. Exploratory PK Endpoints............................................................................8
3.3.2. Drug-Product Acceptability..........................................................................9
3.4. Baseline Variables.....................................................................................................9
3.5. Safety Endpoints .......................................................................................................9
3.5.1. Adverse Events.............................................................................................9
3.5.2. Laboratory Data..........................................................................................10
3.5.3. Vital Signs ..................................................................................................10
3.5.4. Electrocardiograms.....................................................................................10
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................10
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................11
5.1. Hypotheses and Decision Rules ..............................................................................11
5.2. General Methods .....................................................................................................11
5.2.1. Analyses for Binary/Categorical Endpoints ...............................................11
5.2.2. Analyses for Continuous Endpoints ...........................................................11
5.3. Methods to Manage Missing Data ..........................................................................12
5.3.1. PK Concentrations......................................................................................12
5.3.2. PK Parameters ............................................................................................12
6. ANALYSES AND SUMMARIES ......................................................................................13
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 3 of 21
6.1. Primary Endpoints...................................................................................................13
6.2. Secondary Endpoints...............................................................................................13
6.2.1. Safety data ..................................................................................................13
6.2.2. Other PK parameters...................................................................................13
6.2.3. Other Endpoints – Exploratory PK Endpoints............................................15
6.2.4. Drug-Product Acceptability........................................................................15
6.3. Subset Analyses.......................................................................................................15
6.4. Baseline and Other Summaries and Analyses.........................................................15
6.4.1. Demographic Summaries............................................................................15
6.4.2. Study Conduct and Participant Disposition................................................15
6.4.3. Study Treatment Exposure .........................................................................15
6.4.4. Concomitant Medications and Nondrug Treatments..................................16
6.5. Safety Summaries and Analyses .............................................................................16
6.5.1. Adverse Events...........................................................................................16
6.5.2. Laboratory Data..........................................................................................16
6.5.3. Vital Signs ..................................................................................................16
6.5.4. Electrocardiograms.....................................................................................16
7. INTERIM ANALYSES.......................................................................................................16
7.1. Introduction .............................................................................................................17
7.2. Interim Analyses and Summaries............................................................................17
APPENDICES .........................................................................................................................18
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 4 of 21
LIST OF TABLES
Table 1
Summary of Changes..................................................................................5
Table 2.
Plasma PF-07817883 PK Parameter Definitions........................................8
Table 3.
Urine PF-07817883 PK parameter definitions ...........................................9
Table 4.
PK Parameters to be Summarized Descriptively by Treatment ...............14
LIST OF FIGURES
Figure 1.
Study Schema .............................................................................................7
APPENDICES
Appendix 1. Summary of Analyses .........................................................................................18
Appendix 2. SAS Code for Analyses.......................................................................................19
Appendix 3. List of Abbreviations...........................................................................................20
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 5 of 21
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
1. VERSION HISTORY
Table 1
Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
1 /
30 May 2023
Amendment 1
19 Apr 2023
N/A
N/A
2. INTRODUCTION
PF-07817883 is a potent and selective inhibitor of the SARS-CoV-2 Mpro that is currently 
being developed as an oral treatment for patients with COVID-19.
The purpose of the study is to estimate the effect of itraconazole, a strong CYP3A4 inhibitor, 
on the PK of PF-07817883 in healthy adults. Results from this study will provide guidance 
for dosing recommendations with concomitant medications that have CYP3A inhibitory 
potential.
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in Study C5091008.
2.1. Modifications to the Analysis Plan Described in the Protocol
None.
2.2. Study Objectives, Endpoints, and Estimands
The following are the objectives and endpoints in this study. Estimand framework will not 
be applied to this Phase 1 study in healthy participants.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 6 of 21
Objectives
Endpoints
Primary: 
Primary: 
To estimate the effect of multiple doses of 
itraconazole 200 mg QD on the PK of PF-07817883 
following a single oral dose of PF-07817883 300 mg
PF-07817883 plasma PK parameters: Cmax and 
AUCinf (if data permits, otherwise AUClast) with 
itraconazole (test) versus without itraconazole 
(reference)
Secondary: 
Secondary: 

To evaluate the safety and tolerability of PF-
07817883 in healthy participants in the absence and 
presence of multiple doses of itraconazole

To characterize additional PK parameters of PF-
07817883 when administered alone or with 
itraconazole in healthy participants
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, physical exams, and 
12-lead ECGs
PF-07817883 plasma PK parameters: Tmax, and 
if data permits, t½, CL/F, Vz/F, with and without 
coadministration of itraconazole
Tertiary/Exploratory: 
Tertiary/Exploratory: 

To assess the similarity of PK in blood by 
microsampling technique(s) with those in plasma by 
venipuncture

To characterize additional PK parameters of PF-
07817883 following a single oral dose of PF-
07817883 with and without itraconazole by renal 
function

To evaluate the drug-product acceptability of PF-
07817883
Concentration of PF-07817883 in blood and 
plasma as well as PF-07817883 plasma PK 
parameters: AUC12, Cmax
Concentration of PF-07817883 in urine and 
urine PF-07817883 PK parameters: Ae24, CLR, 
if applicable and as data permits
Score on a 14-item drug-product acceptability 
questionnaire
2.3. Study Design
This is a Phase 1, open label, 2-period, fixed sequence study to estimate the effect of the 
strong CYP3A4 inhibitor, itraconazole, on the plasma and urine (if applicable) PK of PF-
07817883 in healthy adult participants. The study will consist of 2 treatments: a single oral 
dose of PF 07817883 300 mg alone and a single oral dose of PF-07817883 300 mg in 
combination with multiple doses of itraconazole 200 mg QD. A total of approximately 12 
healthy adults will be enrolled into the study to ensure at least 10 participants complete the 
study. The treatment will consist of a single fixed sequence. Participants who discontinue 
from the study for non-safety reasons may be replaced at the sponsor’s discretion in
collaboration with the investigator.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 7 of 21
Figure 1.
Study Schema
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoints
The primary endpoints of the study are plasma Cmax and AUCinf (if data permits, otherwise 
AUClast) of PF-07817883 following a single dose administration of PF-07817883 (alone) and 
coadministered with multiple doses of itraconazole. Adjusted geometric mean ratios of Cmax, 
AUCinf and AUClast will be derived.
PK parameters of PF-07817883 will be derived (as data permits) from the concentration-
time data using standard noncompartmental methods as outlined in Table 2. Actual PK 
sampling times will be used in the derivation of PK parameters. In the case that actual PK 
sampling times are not available, nominal PK sampling time will be used in the derivation of 
PK parameters.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 8 of 21
Table 2.
Plasma PF-07817883 PK Parameter Definitions
Parameter
Definition
Method of Determination
Cmax
Maximum observed concentration
Observed directly from data
AUCinf*
Area under the plasma concentration time
curve from time 0 extrapolated to
infinite time
AUClast + (Clast*/kel),
where Clast* is the predicted
plasma concentration at the last
quantifiable time point from the
log-linear regression analysis
AUClast
Area under the plasma concentration-time profile 
from time zero to the time of the last quantifiable 
concentration (Clast).
Linear/Log trapezoidal method.
AUC12
Area under the plasma concentration-time
profile from time zero to 12 hours
Linear/Log trapezoidal method.
AUC24
Area under the plasma concentration-time
profile from time zero to 24 hours
Linear/Log trapezoidal method.
Tmax
Time for Cmax
Observed directly from data as time of 
first occurrence
t½*
Terminal half-life
Loge(2)/kel,
where kel is the terminal phase rate 
constant calculated by a linear 
regression of the loglinear 
concentration-time curve. Only those 
data points judged to describe the 
terminal loglinear decline will be used 
in the regression.
CL/F*
Apparent clearance
Dose/AUCinf
Vz/F*
Apparent volume of distribution
Dose/(AUCinf • kel)
* If data permits.
3.2. Secondary Endpoints
The secondary endpoints include the overall safety profile of a single dose of PF-07817883
alone and with multiple doses of itraconazole, as characterized by adverse events, laboratory 
tests, vital signs, physical exams, and 12-lead ECGs (discussed in Section 3.5).
Other secondary endpoints are additional plasma PK parameters (including Tmax, t1/2, CL/F 
and Vz/F, defined in Table 2) of PF-07817883 (following a single dose administration of PF-
07817883 alone and with multiple doses of itraconazole).
3.3. Other Endpoints
3.3.1. Exploratory PK Endpoints
Blood (by microsampling using the Tasso® M20 device) and urine samples for urine PK 
analysis of PF-07817883 will be taken according to the SoA given in the protocol. For each 
individual, a blood to plasma (B/P) ratio will be calculated by dividing concurrent (i.e. Day 
1, 1 hour post-dose) whole blood PF-07817883 concentration with the plasma PF-07817883 
concentration. A geometric mean and CV% of the B/P ratio from all individuals will also be 
calculated. The plasma equivalent PF-07817883 concentration by microsampling will be 
calculated by dividing with the individual B/P ratio. As a sensitivity analysis, the plasma 
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 9 of 21
equivalent concentration will also be calculated using the geometric mean B/P ratio from all 
individuals. AUC12 and Cmax will be derived from blood samples collected using the Tasso® 
M20 device, and then adjusted for B/P ratio. Concentration of PF-07817883 in urine will be 
analyzed and additional urine PK parameters defined in Table 3 will be derived.
Table 3.
Urine PF-07817883 PK parameter definitions
Parameter
Definition
Method of Determination
Ae24
Total amount of unchanged drug excreted in the 
urine over 24 hours
Sum of amount excreted for each
collection period.
Ae24%
Total amount of unchanged drug excreted in the 
urine over 24 hours, expressed as percent of dose
100×(Ae24/Dose)
CLR
Renal clearance
Ae24/AUC24
3.3.2. Drug-Product Acceptability
Drug product acceptability will be assessed based on participants’ responses to a sponsor-
provided 14-item questionnaire. Each item will be evaluated on a Likert scale with numeric 
categories to capture the level of agreement or disagreement with a statement about drug-
product appearance, palatability, swallowability, or overall impression of taking the drug 
product (1=strongly agree, 5=strongly disagree).
3.4. Baseline Variables
Baseline characteristics will be collected according to the schedule of activities (SoA) as 
specified in the protocol. 
3.5. Safety Endpoints
The following data will be considered in standard safety summaries (see protocol for 
collection days, baseline assessment, and list of parameters): 

Adverse events (AE)

Laboratory data

Vital signs data

ECG results
3.5.1. Adverse Events
Any adverse events occurring following start of treatment will be considered as treatment 
emergent adverse event (TEAE). Events that occur during follow-up within the lag time of 
up to 35 days after the last dose of study intervention will be counted as treatment emergent 
and attributed to the last treatment taken. Events that occur during the washout period 
between study periods will be counted as treatment emergent and attributed to the previous 
treatment taken. The time period for collecting AEs (“active collection period”) for each 
participant begins from the time the participant provides informed consent. 
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 10 of 21
3.5.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol. To determine if there 
are any clinically significant laboratory abnormalities, the haematological, clinical chemistry 
(serum) and urinalysis safety tests will be assessed against the criteria specified in the 
sponsor reporting standards. The assessment will not take into account whether each 
participant’s baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter.
For both periods, the baseline measurement is the last predose measurement prior to 
administration of PF-07817883 in each study period. Changes from baseline will be defined 
as the change between the postdose and baseline measurements.
3.5.3. Vital Signs
Supine blood pressure (BP), pulse rate (PR) and respiratory rate will be measured at times 
specified in the SoA given in the protocol.
For both periods, the baseline measurement is the last predose measurement prior to 
administration of PF-07817883 in each study period. Changes from baseline will be defined 
as the change between the postdose and baseline measurements.
3.5.4. Electrocardiograms
QT interval, QTcF, PR interval, QRS and heart rate (HR) will be recorded at each assessment 
time indicated in the SoA given in the protocol. If not supplied, QTcF will be derived using 
Fridericia’s heart rate correction formula:
QTcF = QT / (RR)^(1/3) where RR = 60/HR (if not provided)
For both periods, the baseline measurement is the last predose measurement prior to 
administration of PF-07817883 in Period 1. Changes from baseline will be defined as the 
change between the postdose ECG measurement and the baseline ECG.
The maximum absolute value (postdose) and the maximum increase from baseline for QTcF, 
PR interval and QRS, over all measurements taken postdose, will be determined.
The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each postdose measurement to give the change from baseline. The maximum of 
these values over the respective period will then be selected, except in the case where a 
participant does not show an increase. In such an instance, the minimum decrease should be 
taken.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to releasing the database and classifications will 
be documented per standard operating procedures.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 11 of 21
Participant Analysis Set
Description
Enrolled 
"Enrolled" means a participant's, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process and 
assignment to study intervention. Potential participants who 
are screened for the purpose of determining eligibility for the 
study, but do not participate in the study, are not considered 
enrolled, unless otherwise specified by the protocol. A 
participant will be considered enrolled if the informed consent 
is not withdrawn prior to participating in any study activity.
Safety Analysis Set
All participants enrolled and who take at least 1 dose of study
intervention.
PK Concentration Set
All participants who take at least 1 dose of study intervention 
and in whom at least 1 concentration value is reported.
PK Parameter Set
All participants who take at least 1 dose of study intervention 
and in whom at least 1 of the PK parameters of primary 
interest are reported.
5. GENERAL METHODOLOGY AND CONVENTIONS
Final analysis will be performed after study participant data set release following last 
participant last visit.
5.1. Hypotheses and Decision Rules
No statistical hypothesis will be tested in this study.
5.2. General Methods
5.2.1. Analyses for Binary/Categorical Endpoints
For binary or categorical variables, number of participants, numbers and percentages of 
participants meeting the categorical criteria will be presented in accordance with the Clinical 
Data Interchange Standards Consortium and Pfizer Standards (CaPS).
5.2.2. Analyses for Continuous Endpoints
For continuous variables, the data will be summarized using the number of participants, 
mean, median, standard deviation (SD), minimum, and maximum in accordance with the 
CaPS. For appropriate PK parameters, geometric mean and geometric coefficient of variation 
(%CV) will also be summarized.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 12 of 21
5.3. Methods to Manage Missing Data
5.3.1. PK Concentrations
Methods to handle missing PK data are described below. 
Concentrations Below the Limit of Quantification:
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. (In listings BLQ values will be reported as “<LLQ” where LLQ 
will be replaced with the value for the lower limit of quantification.).
Deviations, Missing Concentrations and Anomalous Values:
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if one of the following cases is true:
1. A concentration has been collected as ND (i.e., not done) or NS (i.e., no sample).
2. A deviation in sampling time (time deviation > 20%) is of sufficient concern or a 
concentration has been flagged as anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
An anomalous concentration value is one that, after verification of bioanalytical validity, is 
grossly inconsistent with other concentration data from the same individual or from other 
participants. For example, a BLQ concentration that is between quantifiable values from the 
same dose is considered as anomalous. Anomalous concentration values may be excluded 
from PK analysis at the discretion of the PK analyst or pharmacokineticist.
5.3.2. PK Parameters
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a participant’s concentration data, the parameter will be coded as NC 
(i.e., not calculated). (Note that NC values will not be generated beyond the day that a 
participant discontinues). In summary tables, statistics will be calculated by setting NC 
values to missing; and statistics will be presented for a particular treatment with ≥3 evaluable 
measurements. PK parameter analyses will not be performed for a particular parameter if 
more than 50% of the data are NC.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event such as vomiting before all the compound is adequately absorbed 
from the gastrointestinal tract), this will be footnoted in summary tables and will not be 
included in the calculation of summary statistics or statistical analyses.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 13 of 21
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoints
The primary endpoints Cmax and AUCinf (if data permits, otherwise AUClast) will be
summarized descriptively by treatment and will include the set of summary statistics as 
specified in Table 4. Box and whisker plots for individual participant parameters (Cmax, 
AUCinf and AUClast) will be plotted by treatment and overlaid with geometric means.
Natural log transformed parameters Cmax and AUCinf (if data permits, otherwise AUClast) of 
PF-07817883 will be analyzed using a mixed effect model with treatment as fixed effect and 
participant as a random effect. Estimates of the adjusted means, adjusted mean differences 
(Test-Reference) and corresponding 90% CIs will be obtained from the model. The adjusted 
mean differences and 90% CIs for the differences will be exponentiated to provide estimates 
of the ratio of adjusted geometric means (Test/Reference) and 90% CI for the ratios. 
PF-07817883 administered alone will be the Reference treatment and PF-07817883 
co-administered with itraconazole will be the Test treatment.
For Cmax, AUCinf and AUClast, a listing of the individual participant ratios (Test/Reference) 
will be provided. 
Residuals from the model will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the CSR. If there are major deviations from 
normality or outliers then the effect of these on the conclusions will be investigated through 
alternative transformations and/or analyses excluding outliers. Justification for any 
alternative to the planned analysis will be provided in the clinical study report.
6.2. Secondary Endpoints
6.2.1. Safety data
Safety data will be analyzed in accordance with the CaPS (described in Section 6.5).
6.2.2. Other PK parameters
Tmax, t1/2, CL/F and Vz/F will be summarized descriptively by treatment and will include the 
set of summary statistics as specified in Table 4. 
PK parameter summaries:
The PF-07817883 PK parameters will be summarized descriptively by treatment in 
accordance with Pfizer data standards for the PK Parameter Set, as data permit. Missing 
values will be handled as detailed in Section 5.3.2. Each PF-07817883 PK parameter will be 
summarized by treatment and will include the set of summary statistics as specified in
Table 4.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 14 of 21
Table 4.
PK Parameters to be Summarized Descriptively by Treatment 
Parameter
Summary Statistics
AUCinf, AUClast, 
AUC12, AUC24, 
Cmax, CL/F, Vz/F, 
Ae24, Ae24%, CLR
N, arithmetic mean, median, SD, %CV, minimum, maximum, geometric mean and 
geometric %CV
Tmax
N, median, minimum, maximum
t½
N, arithmetic mean, median, SD, %CV, minimum, maximum
N: Number of participants contributing to the summary statitics
Supporting data from the estimation of t½ and AUCinf will be listed by treatment: terminal 
phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2); the 
percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of
time points used in the estimation of kel. This data may be included in the clinical study
report.
PK concentration summaries:
The plasma concentrations of PF-07817883 will be listed and descriptively summarized by 
nominal PK sampling time and treatment for the PK Concentration Set. Individual participant 
and summary profiles (mean and median plots) of the plasma concentration-time data will be 
plotted by treatment using actual and nominal times, respectively. Mean and median PF-
07817883 plasma concentration profiles will be presented on both linear and semi-log scales. 
Presentations for PF-07817883 plasma concentrations will include:

A listing of all concentrations sorted by participant ID, treatment and nominal time 
postdose. The concentration listing will also include the actual times. Deviations from the 
nominal time will be provided in a separate listing.

A summary of concentrations by treatment and nominal time postdose, where the set of 
statistics will include n, mean, median, SD, %CV, minimum, maximum and the number 
of concentrations above the LLQ.

Median concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by treatment (all treatments on the same plot per scale, based on the 
summary of concentrations by treatment and time postdose).

Mean concentrations time plots (on both linear and semi-log scales) against nominal time 
postdose by treatment (all treatments on the same plot per scale, based on the summary of 
concentrations by treatment and time postdose).

Individual concentration time plots by treatment (on both linear and semi-log scales) 
against actual time postdose (there will be separate spaghetti plots for each treatment per 
scale).
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 15 of 21

Individual concentration time plots by participant (on both linear and semi-log scales) 
against actual time postdose [there will be separate plots for each participant (containing 
all treatments) per scale].
6.2.3. Other Endpoints – Exploratory PK Endpoints
AUC12 and Cmax derived from blood samples collected using the Tasso® M20 device
adjusted for B/P ratio will be summarized for PF-07817883 (administered alone in Period 1)
and will include the set of summary statistics as specified in Table 4. Summary statistics of  
the whole blood concentrations, plasma equivalent concentrations by microsampling using 
individual B/P ratio and plasma equivalent concentrations by microsampling using geometric 
mean B/P ratio at nominal time of collection as defined in SoA will be calculated.
Furthermore, to determine correlation in concentrations derived from time matched Tasso®
M20 microsampling (calculated using individual or population) and traditional venous 
plasma sampling, Bland-Altman plot analysis will be performed to evaluate the bias and SD 
of the bias between the mean differences and to estimate an agreement interval within a 95% 
confidence limit. A concentration correlation analysis will be conducted with the same 
dataset.
In addition, Ae24, Ae24% and CLR, derived from PF-07817883 concentrations measured from 
urine samples collected (if analyzed) will be summarized by treatment and will include the 
set of summary statistics as specified in Table 4.
6.2.4. Drug-Product Acceptability
For each item in the Drug-Product Acceptability Questionnaire, summary statistics will 
include number and percent with each numeric score (1,2,3,4,5) and negative (1, 2), neutral 
(3) and positive (4, 5) scores and will be presented by item and domain (Appearance, 
Mouthfeel, Taste, Swallowability and Overall assessment).
6.3. Subset Analyses
There are no planned subset analyses.
6.4. Baseline and Other Summaries and Analyses
6.4.1. Demographic Summaries
Demographic characteristics will be summarized for enrolled population in accordance with 
the CaPS.
6.4.2. Study Conduct and Participant Disposition
Participants evaluation groups will show end of study participant disposition. Frequency 
counts will be supplied for participant discontinuation(s) by treatment. Data will be reported 
in accordance with the CaPS.
6.4.3. Study Treatment Exposure
Study treatment exposure will be listed.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 16 of 21
6.4.4. Concomitant Medications and Nondrug Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be reported in the 
listings.
6.5. Safety Summaries and Analyses
All safety analyses will be performed on the Safety Analysis Set.
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
Safety data will be summarized for three (3) separately defined treatments: (i) PF-07817883 
300 mg SD (from Period 1 Day 1 up to just before the first dose of itraconazole administered 
alone in Period 2 Day 1), (ii) itraconazole 200 mg QD alone (from first dose of itraconazole 
administered alone in Period 2 Day 1 up to just before coadministration of PF-07817883 in 
Period 2 Day 4), and (iii) itraconazole 200 mg QD with PF-07817883 300 mg SD (from 
coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the 
study).
A set of summary tables split by these 3 treatments will be produced to evaluate any potential 
risk associated with the safety and tolerability of administering PF-07817883 300 mg SD 
alone, itraconazole 200 mg QD alone, and PF-07817883 300 mg SD in the presence of 
itraconazole 200 mg QD.
6.5.1. Adverse Events
Adverse events will be reported in accordance with the CaPS.
Participant discontinuations due to adverse events will be detailed by treatment. Data will be 
reported in accordance with the CaPS.
6.5.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the CaPS.
6.5.3. Vital Signs
Vital signs data will be listed and summarized by treatment in accordance with the CaPS.
6.5.4. Electrocardiograms
ECG data will be listed and summarized by treatment in accordance with the CaPS.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study. As this is an open-label study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK modeling, and/or supporting clinical 
development.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 17 of 21
7.1. Introduction
Not applicable.
7.2. Interim Analyses and Summaries
Available safety and PK data may be reviewed.
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 18 of 21
APPENDICES
Appendix 1. Summary of Analyses
Endpoint
Population
Data Inclusion and Rules 
for Handling 
Intercurrent Events and 
Missing Data 
Analysis Method
Ratio of PF-
07817883 Cmax, 
AUCinf and AUClast
PK Parameter 
Set
Observed data
Mixed effect 
ANOVA model
PF-07817883 PK 
parameters
PK Parameter 
Set
Observed data and imputed 
(Section 5.3.2) data
Descriptive 
statistics
PF-07817883 
concentrations
PK 
Concentration 
Set
Observed and imputed 
(Section 5.3.1) data
Descriptive 
statistics
Safety data
Safety Analysis 
Set
Observed data
Descriptive 
statistics
Drug-product 
acceptability data
Safety Analysis 
Set
Observed data
Descriptive 
statistics
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 19 of 21
Appendix 2. SAS Code for Analyses
An example of the PROC MIXED code is provided below:
For the primary objective:
proc mixed data=tab.pk;
class trt participant;
model log&var=trt / ddfm=KR;
random participant / subject=participant;
lsmeans trt;
estimate 'B vs A' trt  -1  1  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
/* Letter assignments for treatments (trt) within the estimate statement above are as follows
A: single dose of PF-07817883 300 mg (reference)
B: multiple doses of itraconazole 200 mg QD + single dose of PF-07817883 300 mg (test)
*/
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 20 of 21
Appendix 3. List of Abbreviations
Abbreviation
Term
%CV
coefficient of variation
AE
adverse event
Ae24
cumulative total amount of drug recovered unchanged in the urine, 
from time 0 to 24 hours
Ae24%
cumulative total amount of drug recovered unchanged in the urine, 
from time 0 to 24 hours, expressed as percent of dose
ANOVA
analysis of variance
AUC12
area under the plasma concentration-time curve from time 0 to the 
time 12 hours
AUC24
area under the plasma concentration-time curve from time 0 to the 
time 24 hours
AUCextrap%
the percent of AUCinf based on extrapolation
AUCinf
area under the plasma concentration-time profile from time zero 
extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time zero to 
the time of the last quantifiable concentration
BLQ
below the limit of quantitation
B/P
blood to plasma
BP
blood pressure
CaPS
Clinical Data Interchange Standards Consortium and Pfizer 
Standards
CI
confidence interval
CL/F
apparent clearance
Clast
predicted plasma concentration at the last quantifiable time point 
from the log-linear regression analysis
CLR
renal clearance
Cmax
maximum plasma concentration
COVID-19
coronavirus disease 2019
CSR
clinical study report
CYP3A
cytochrome P450, family 3, subfamily A
ECG
electrocardiogram
HR
heart rate
kel
elimination rate constant estimated from the log-linear regression 
analysis
LLQ
lower limit of quantitation
Mpro
main protease
ms
milliseconds
N/A
not applicable
NC
not calculated
ND
not done
NS
no sample
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)


Protocol C5091008 (PF-07817883) Statistical Analysis Plan
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022
PFIZER CONFIDENTIAL
TMF Doc ID: 98.03
Page 21 of 21
Abbreviation
Term
PK
pharmacokinetic(s)
PR
pulse rate
PR interval
time from the beginning of the P wave to the beginning of the QRS 
complex
QD
once a day
QRS
Combination of Q-, R- and S- wave on an electrocardiogram 
representing ventricular depolarization
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
r2
goodness of fit statistic from the log-linear regression
RR interval
the time between the start of one QRS complex and the start of the 
next QRS complex
SAP
statistical analysis plan
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SD
standard deviation; single dose
SoA
schedule of activities
t1/2
terminal plasma elimination half-life
TEAE
treatment emergent adverse event
Tmax
time for Cmax
Vz/F
apparent volume of distribution after oral dose
090177e1a060b885\0.1\Draft\Versioned On:08-Apr-2024 07:41 (GMT)