Conditions: Healthy Participants
Keywords: PF-07293893 Single ascending dose Safety Tolerability Pharmacokinetics
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 30
Healthy volunteers: yes

Brief summary:
The purposes of the study are:

To learn about the safety and tolerability of study medicine (PF-07293893). Tolerability is the extent to which side effects can be tolerated. Side effects are unwanted reactions to the study medicine.

To measure the amount of PF-07293893 in blood after the medicine is taken by mouth.

The study is seeking participants who:

* Are females of non-childbearing potential and males 18 to 65 years of age
* Are in generally healthy condition
* Have not had viral infections (HIV, HBV or HCV). HIV, human immunodeficiency virus. HBV, human hepatitis B virus. HCV, human hepatitis C virus.

Participants will receive either PF-07293893 or placebo (dummy pill) by chance. Participants will undergo up to 4 treatments periods in this study. Everyone will receive up to 4 doses of study medicine and up to 2 doses of placebo. In each period, participants will stay in study clinic for 5 days. There will be at least 2 days between each treatment period.

Participants will be involved in this study for about 14 weeks. During their stay, participants will undergo several examinations. Participants will also have their blood collected by the study doctors for several times.

Detailed description:

Arms:
arm 1: Single dose administration of PF-07293893 and placebo; Within a cohort, participants will receive up to 4 doses of PF-07293893 and up to 2 doses of placebo. arm 2: Single dose administration of PF-07293893 and placebo; Within a cohort, participants will receive up to 4 doses of PF-07293893 and up to 2 doses of placebo. arm 3: Single dose administration of PF-07293893 and placebo; Within a cohort, participants will receive up to 4 doses of PF-07293893 and up to 2 doses of placebo.

Interventions: intervention 1: PF-07293893 intervention 2: Placebo
Intervention descriptions: intervention 1: PF-07293893 will be prepared as an oral suspension given in escalating single doses to be determined. intervention 2: Matching placebo will be prepared as an oral suspension given in each cohort.

Protocol document:
Prot_000.pdf: 
P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1
Title P a ge
A P H A S E 1, R A N D O MI Z E D, D O U B L E -B LI N D, S P O N S O R -O P E N, P L A C E B O -
C O N T R O L L E D, 4 -P E RI O D, C R O S S O V E R, FI R S T -I N-H U M A N S T U D Y T O E V A L U A T E 
T H E S A F E T Y, T O L E R A BI LI T Y, A N D P H A R M A C O KI N E TI C S O F SI N G L E 
A S C E N DI N G O R A L D O S E S O F P F -0 7 2 9 3 8 9 3 A D MI NI S T E R E D T O H E A L T H Y A D U L T 
P A R TI CI P A N T S
St u d y I nter ve nti o n N u m ber :
P F - 0 7 2 9 3 8 9 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:
N A
E U C T N u m ber:
2 0 2 3 - 5 0 4 9 2 1- 3 7- 0 0
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 1 7 1 0 0 1
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1 U S A
Brief Title:
A St u d y  t o Lear n A b o ut t he St u d y Me dici ne Calle d P F - 0 7 2 9 3 8 9 3 i n Healt h y  A d ults, a n d 
H o w Differe nt D oses of St u d y  Me dici ne are T olerate d a n d Act i n t he B o d y. 
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nt s, yo u a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or 
use it f or u na ut h orize d p ur p oses. I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 1
0 7 J u ne 2 0 2 3
Ori gi nal pr ot oc ol
2 8 A pril 2 0 2 3
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs a n d a n y 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 ge T a ble
A m e n d me nt 1 ( 0 7 J u ne 2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt: T his a me n d me nt a d de d a secti o n f or electr o nic 
c o nse nt, defi niti o ns f or S A R a n d S U S A R, details re gar di n g ha n dli n g missi n g safet y a n d P K 
data , a n d details re gar di n g c o nsi derati o n of i n di vi d ual e x p os ures i n a d diti o n t o mea n 
e x p os ures f or d ose escalati o n a n d P K st o p pi n g li mits .
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 S ecti o n 1 0. 1. 3. 1 t o 
descri be t he electr o nic 
c o nse nt pr ocess
Partici pa nts ma y  be a ble t o 
e x perie nce t he i nf or me d 
c o nse nt pr ocess b y 
electr o nic mea ns (e C o nse nt)
1 0. 1. 3. 1 ( Electr o nic 
C o nse nt)
A d de d S ecti o ns 1 0. 3. 3 a n d 
1 0. 3. 4 t o defi ne S A R a n d 
S U S A R, res pecti vel y.
S A R a n d S U S A R are 
defi ne d t o pr o vi de m ore 
clarit y 
1 0. 3. 3 ( Defi niti o n of S A R)
1 0. 3. 4 ( Defi niti o n of 
S U S A R)
U p date d d ose escalati o n a n d 
st o p pi n g r ule t o c o nsi der 
ma xi m u m i n di vi d ual 
e x p os ure i n a d diti o n t o 
mea n e x p os ure f or d ose 
escalati o n.
T o a v oi d e x p osi n g 
partici pa nts t o e x p os ures 
hi g her t ha n P K st o p pi n g 
li mits.
6. 6. 1 ( D ose Escalati o n a n d 
St o p pi n g R ules)
N o n -s u bst a nti al M o dific ati o n(s)
A descri pti o n of h o w 
missi n g safety a n d P K 
o bser vati o ns will be ha n dle d
is a d de d.
T o pr o vi de clarit y o n h o w 
t he missi ng safet y a n d P K 
o bser vati o ns will be 
ha n dle d.
Secti o n 9. 3 ( Statistical 
A nal y ses)
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................4 8
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................4 8
7. 3. L ost t o F oll o w -U p ...................................................................................................4 9
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...............................................................4 9
8. 1. A d mi nistrati ve Pr oce d ures ......................................................................................4 9
8. 2. Efficac y  Assess me nts..............................................................................................5 0
8. 3. Safet y Assess me nts .................................................................................................5 0
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 1
8. 3. 2. Ne ur ol o gical E xa mi nati o n ..........................................................................5 1
8. 3. 3. Vital Si g ns ..................................................................................................5 1
8. 3. 3. 1. Bl o o d Press ure a n d P ulse Rate ..................................................5 1
8. 3. 3. 2. Res pirat or y  Rate........................................................................5 2
8. 3. 3. 3. Te m perat ure ..............................................................................5 2
8. 3. 4. Electr ocar di o gra ms..................................................................................... 5 2
8. 3. 4. 1. C o nti n u o us Car diac M o nit ori n g b y Tele metr y .........................5 3
8. 3. 5. Cli nical Safet y  La b orat or y Assess me nts....................................................5 3
8. 3. 6. C O VI D - 1 9 S pecific Assess me nts...............................................................5 4
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g .................5 4
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n....... 5 5
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................5 5
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 5
8. 4. 2. M et h o d of Detecti n g A Es a n d S A Es ..........................................................5 6
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................5 6
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................5 6
8. 4. 5. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure .....................................................5 7
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................5 7
8. 4. 5. 2. E x p os ure D u ri n g Breastfee di n g ................................................5 8
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................5 9
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................5 9
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 9
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 5 9
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6
8. 4. 8. 1. Lac k of Eff icac y........................................................................5 9
8. 4. 9. Me dical De vice Deficie ncies ......................................................................5 9
8. 4. 1 0. Me dicati o n Err ors .....................................................................................5 9
8. 5. P har mac o ki netics ....................................................................................................6 0
8. 5. 1. Plas ma f or A nal ys is of P F-0 7 2 9 3 8 9 3 C o nce ntrati o n .................................6 0
8. 6. Ge netics ...................................................................................................................6 1
8. 6. 1. S pecifie d Ge netics ......................................................................................6 1
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics ...................................................6 2
8. 7. Bi o mar kers ..............................................................................................................6 2
8. 7. 1. S pecifie d Ge ne E x pressi o n ( R N A) Researc h .............................................6 2
8. 7. 2. S pecifie d Pr otei n Researc h .........................................................................6 2
8. 7. 3. S pecifie d Meta b ol o mic Researc h ...............................................................6 2
8. 7. 4. Retai ne d Researc h Sa m ples f or Bi o mar kers ...............................................6 2
8. 7. 5. Plas ma f or A nal ys is of Bi o mar ker(s) of Tra ns p orter Acti vit y ...................6 2
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................6 3
8. 9. Healt h Ec o n o mics ...................................................................................................6 3
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 6 3
9. 1. Statistical H y p ot hesis ..............................................................................................6 3
9. 2. A nal y sis Sets ...........................................................................................................6 3
9. 3. Statistical A nal y ses .................................................................................................6 4
9. 3. 1. Safet y A nal ys es ..........................................................................................6 4
9. 3. 1. 1. Electr ocar di o gra m A nal y ses......................................................6 4
9. 3. 2. P K A nal y ses................................................................................................6 5
9. 3. 2. 1. D eri vati o n of P F -0 7 2 9 3 8 9 3 P K Para meters ..............................6 5
9. 3. 2. 2. Statistical Met h o ds f or P K Data................................ ................6 6
9. 3. 3. Tertiar y / E x pl orat or y E n d p oi nt(s) A nalys is ................................................6 6
9. 3. 4. Ot her A nal ys es ............................................................................................6 7
9. 4. I nteri m A nal ys es .....................................................................................................6 7
9. 5. Sa m ple Size Deter mi nati o n................................ .....................................................6 7
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ..........................................................................6 8
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 8
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................6 8
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 8
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................6 9
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................6 9
1 0. 1. 3. 1. Electr o nic C o nse nt ................................ ..................................7 0
1 0. 1. 4. Data Pr otecti o n .........................................................................................7 0
1 0. 1. 5. C o m mittees Str uct ure ...............................................................................7 0
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ...................................................7 0
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ......................................................7 0
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................7 2
1 0. 1. 8. S o urce D oc u me nts ....................................................................................7 3
1 0. 1. 9. Use of Me dical Rec or ds ............................................................................7 3
1 0. 1. 1 0. St u d y  a n d Site Start a n d Cl os ure ............................................................7 4
1 0. 1. 1 1. P u blicati o n P olic y ...................................................................................7 4
1 0. 1. 1 2. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................7 5
1 0. 2. A p pe n di x 2: Cli n ical La b orat or y Tests.................................................................7 6
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 9
1 0. 3. 1. Defi niti o n of A E .......................................................................................7 9
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................8 0
1 0. 3. 3. Defi niti o n of S A R..................................................................................... 8 1
1 0. 3. 4. Defi niti o n of S U S A R................................................................................ 8 2
1 0. 3. 5. Rec or di n g/ Re p orti n g a n d F oll o w- U p of A Es a n d/ or S A Es D uri n g 
t he Acti ve C ollecti o n Peri o d............................................................................8 2
1 0. 3. 6. Re p orti n g of S A Es ....................................................................................8 5
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................8 7
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 8 7
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................8 7
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................8 7
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................8 8
1 0. 5. A p pe n di x 5: Ge netics ............................................................................................9 1
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts .......9 2
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8
1 0. 7. A p pe n di x 7: Ki d ne y  Safet y: M o nit ori n g G ui deli nes ............................................9 4
1 0. 7. 1. La b orat or y  Assess me nt of C ha n ge i n Ki d ne y F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y ..............................................................................9 4
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...............9 4
1 0. 7. 2. 1. A d ults ( 1 8 Years a n d A b o ve) — 2 0 2 1 C K D - E PI 
E q uati o ns........................................................................................... 9 4
1 0. 7. 3. Ki d ne y  F u ncti o n Calc ulati o n T o ols..........................................................9 4
1 0. 7. 4. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ...................................................................................................9 5
1 0. 8. A p pe n di x 8: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ...................................9 6
1 0. 9. A p pe n di x 9: Pr o h i bite d C o nc o mita nt Me dicati o ns T hat Ma y Res ult i n D DI.......9 8
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns .............................................................................1 0 0
1 1. R E F E R E N C E S ................................................................................................................1 0 5
LI S T O F T A B L E S
Ta ble 1.
St u d y  Sc he d ule of Assess me nt.................................................................1 5
Ta ble 2.
St u d y  Sc he d ule of Assess me nts f or P K, Vitals,  E C Gs a n d Ot her o n 
D a y  1 of Eac h Peri o d................................................................................1 9
Ta ble 3.
Pre dicte d H u ma n E x p os ures a n d Safet y  Mar gi ns at Pr o p ose d Si n gle 
D oses of P F - 0 7 2 9 3 8 9 3 .............................................................................2 9
Ta ble 4.
Plas ma P F -0 7 2 9 3 8 9 3 P K Para meters .......................................................6 5
Ta ble 5.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts.............................................7 7
LI S T O F FI G U R E S
Fi g ure 1 St u d y Desi g n Sc he ma a, b,c...........................................................................................1 4
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: 
A P hase 1, Ra n d o mize d, D o u ble- Bli n d, S p o ns or -O pe n, Place b o -C o ntr olle d, 4 -Peri o d, 
Cr oss o ver, First -i n-H u ma n St u d y  t o E val uate t he Safet y, T olera bility, a n d P har mac o ki netics 
of Si n gle Asce n di n g Oral D oses of P F -0 7 2 9 3 8 9 3 A d mi nistere d t o Healt h y  A d ult 
Partici pa nts.
Brief Title:
A St u d y  t o Lear n A b o ut t he St u d y Me dici ne Calle d P F -0 7 2 9 3 8 9 3 i n Healt h y  A d ults, a n d 
H o w Differe nt D oses of St u d y  Me dici ne are T olerate d a n d Act i n t he B o d y .
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:
N A
E U C T N u m ber:
2 0 2 3 -5 0 4 9 2 1 -3 7 -0 0
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 1 7 1 0 0 1
P h ase:
1
R ati o n ale :
T his st u d y  is t he first cli nical st u d y wit h P F-0 7 2 9 3 8 9 3. T he safet y, t olera bilit y , a n d plas ma 
p har mac o ki netics ( P K ) of P F -0 7 2 9 3 8 9 3 after a d mi nistr ati o n of escalati n g, si n gle, oral d oses 
will be e val uate d.
O bjecti ves a n d E n d p oi nts :
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y:

T o e val uate t he safet y a n d t olera bilit y of si n gle asce n di n g d oses 
of P F - 0 7 2 9 3 8 9 3 a d mi nistere d orall y t o healt h y a d ult 
partici pa nts.
Assess me nt of a d verse e ve nts, cli nical safet y 
la b orat or y tests, vital si g ns, c o nti n u o us car diac 
m o nit ori n g, 1 2 -lea d electr ocar di o gra ms,
p h ysical e xa mi nati o ns a n d ne ur ol o gical 
e xa mi n ati o ns.
Sec o n d ar y: 
Sec o n d ar y:

T o e val uate t he P K of P F -0 7 2 9 3 8 9 3 f oll o wi n g si n gle d oses of 
P F - 0 7 2 9 3 8 9 3 a d mi nistere d orall y t o healt h y a d ult partici pa nts.
P K para meters deri ve d fr o m plas ma 
P F -0 7 2 9 3 8 9 3 c o nce ntrati o ns: C ma x , Tma x , 
A U C last, a n d if data per mit, A U Ci nf, a n d t½ .
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0
O ver all Desi g n :
T his is a ra n d o mize d, i n vesti gat or - a n d partici pa nt -bli n d, s p o ns or -o pe n, place b o -c o ntr olle d, 
first-i n-h u ma n, si n gle asce n di n g oral d ose, 4 -peri o d, cr oss o ver st u d y  of P F- 0 7 2 9 3 8 9 3 
a d mi nistere d t o healt h y a d ult partici pa nts. A p pr o xi matel y 2 4 healt h y a d ult partici pa nts ( u p t o 
3 c o h orts of a p pr o xi matel y  8 partici pa nts eac h) will be e nr olle d i n t his st ud y. T he first 
2 c o h orts are pla n ne d, a n d t he t hir d c o h ort is o pti o nal. I n eac h peri o d, partici pa nts will be 
ra n d o mize d t o eit her P F- 0 7 2 9 3 8 9 3 or place b o i n a rati o of 3: 1. Eac h partici pa nt is pla n ne d t o 
u n der g o u p t o 4 treat me nt peri o ds recei vi n g u p t o 4 d o ses of P F-0 7 2 9 3 8 9 3 a n d u p t o 2 d oses 
of place b o. Preca uti o nar y  se nti nel d osi n g will be use d i n a n y peri o d e val uati n g escalati n g 
d oses of P F -0 7 2 9 3 8 9 3 a n d ma y  be o mitte d f or peri o ds w he n re peati n g a d ose le vel or 
a d mi nisteri n g a l o wer d ose le vel t ha n pre vi o u sl y e val uate d. F or peri o ds wit h se nti nel d osi n g, 
t w o partici pa nts ( 1 recei vi n g P F-0 7 2 9 3 8 9 3 a n d 1 recei vi n g place b o) will be d ose d i nitiall y  
bef ore t he re mai ni n g partici pa nts of t hat peri o d are d ose d. Safet y a n d t olera bilit y  data 
t hr o u g h at least 2 4 h o urs post -d ose f or t he se nti nel partici pa nts will be re vie we d pri or t o 
d osi n g t he re mai ni n g partici pa nts of t hat peri o d.
Base d o n t he re vie w of e mer gi n g safet y, t olera bilit y , a n d P K data i n C o h orts 1 a n d 2, t he 
re mai ni n g peri o ds of C o h ort 2 a n d/ or a n o pti o nal t hir d c o h ort e nr olli n g a p pr o xi matel y 
8 partici pa nts (cr oss o ver, place b o -c o ntr olle d desi g n) ma y be use d t o e x pl ore a d diti o nal 
d oses, t o re peat a d ose, or t o e val uate effect of cr ystalli ne f or m o n P F -0 7 2 9 3 8 9 3 P K i n faste d 
a n d/ or fe d state.  
D osi n g will occ ur i n t he faste d state f or all peri o ds, e xce pt if a n o pti o nal e x pl orat or y 
assess me nt of t he effect of f o o d o n cr y stalli ne P F-0 7 2 9 3 8 9 3 P K is c o n d ucte d.
N u m ber of P artici p a nts:
A p pr o xi matel y  1 6 ( C o h orts 1 a n d 2) or 2 4 ( wit h o pti o nal C o h ort 3) healt h y a d ult partici pa nts 
(a p pr o xi matel y 8 partici pa nts per c o h ort) 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 a gree me nt t o partici pate i n a cli nical st u d y  f oll o wi n g 
c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d ra n d o mizati o n/assi g n ment t o st u d y  
i nter ve nti o n.
St u d y P o p ul ati o n :
K e y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
Partici pa nts m ust meet t he f oll o wi n g ke y  i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
1.
Fe males of n o n -c hil d beari n g p ote ntial a n d males 1 8 t o 6 5 y ears of a ge, i ncl usi ve, at 
t he ti me of si g ni n g t he i nf or me d c o nse nt d oc u me nt (I CD) w h o are o vertl y  healt h y as 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 1
deter mi ne d b y me dical e val uati o n i ncl u di n g me dical hist or y, p h ys ical e xa mi nati o n, 
la b orat or y tests, a n d car diac m o nit ori n g.
2.
B o d y mass i n de x ( B MI ) of 1 6 t o 3 0. 5 k g/ m 2; a n d a t otal b o d y wei g ht > 5 0 k g ( 1 1 0 l b). 
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my). 

Hist or y  of h u ma n i m m u n o deficie nc y  vir us (HI V) i nfecti o n, he patitis B, or 
he patitis C; p ositi ve testi n g f or HI V, he patitis B s urface a nti ge n ( H Bs A g ), or 
he patiti s C a nti b o d y (H C V A b ). He patitis B vacci nati o n is all o we d.
2.
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 or sit uati o ns 
relate d t o c or o na vir us d isease 2 0 1 9 (C O VI D - 1 9) pa n de mic  t hat ma y  i ncrease t he ris k 
of st u d y  partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt 
i na p pr o priate f or t he st u d y. 
3.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n, wit h t he 
 
 w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o 
t he first d ose of st u d y i nter ve nti o n.
4.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y  i nter ve nti o n use d i n t his st u d y ( w hic he ver is l o n ger). Partici pati o n i n 
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d uri n g t heir 
partici pati o n i n t his st u d y .
5.
Scree ni n g s u pi ne bl o o d press ure ( B P ) ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g 
( diast olic) f or partici pa nts < 6 0 years; a n d ≥1 5 0/ 9 0 m m/ H g f or partici pa nts ≥6 0 y ears 
ol d, f oll o wi n g at least 5 mi n utes of s u pi ne rest.
6.
Re nal i m pair me nt as defi ne d b y  a n esti mate d gl o mer ular filtrati o n rate ( e G F R )
< 7 5 m L /mi n/ 1. 7 3 m². Si nce partici pa nts are 1 8 ye ars t o 6 5 years, 2 0 2 1 c hr o nic ki d ne y 
disease e pi de mi ol o g y (C K D -E PI ) e G F R (c o m bi ne d ser u m creati ni ne [Screat ] a n d 
ser u m c ystati n C [Sc y s]) is t he rec o m me n de d f or m ula.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 2
7.
Sta n dar d 1 2 -lea d electr ocar di o gra m (E C G ) t hat de mo nstrates cli nicall y  rele va nt 
a b n or malities t hat ma y affect partici pa nt safety or i nter pretati o n of st u d y res ults (e g, 
Q Tc F > 4 5 0 ms, c o m plete left b u n dle bra nc h bl oc k (L B B B ), si g ns of a n ac ute or 
i n deter mi nate- a ge m y ocar dial i nfarcti o n, S T -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 atri o ve ntric ular ( A V ) bl oc k, or seri o us 
bra d yarr h yt h mias or tac h y arr h yt h mias).
8.
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 h e st u d y s pecific la b orat or y a n d c o nfir me d by a si n gle 
re peat test, if dee me d necessar y: 

Ala ni ne a mi n otra nsferase (A L T ), as partate a mi n otra nsferase (A S T ), t otal 
bilir u bi n ≥1. 0 5 × u p per li mit of n or mal (U L N ), partici pa nts wit h a hist or y  of 
Gil bert’s s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or 
t his st u d y pr o vi de d t he direct bilir u bi n le vel is ≤U L N .
9.
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 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 fa mil y 
me m bers. 
St u d y Ar ms a n d D ur ati 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 tele p h o ne f oll o w- u p c o ntact will be a p pr o xi matel y  1 4 wee ks f or eac h partici pa nt.
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F -0 7 2 9 3 8 9 3
Place b o
Use
E x peri me ntal
Place b o
I M P or 
NI M P/ A x M P
I M P
I M P
D ose F or m ul ati o n
B ul k p o w der f or e xte m p ora ne o us pre parati o n 
of oral s us pe nsi o ns
B ul k p o w der f or e xte m p ora ne o us pre parati o n 
of oral s us pe nsi o ns
U nit D ose 
Stre n gt h(s)
Pl a n ne d oral s us pe nsi o n d oses ra n gi n g fr o m 
1 0 -1 5 0 0 m g
0 m g
R o ute of 
A d mi nistr ati o n
Oral
Oral
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 3
St u d y Ar m(s)
Ar m Title
C o h ort 1
C o h ort 2
C o h ort 3 ( O pti o nal )
Ar m 
Descri pti o n
Partici pa nts will recei ve u p t o 4 
d oses of P F - 0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g place b o. 
D oses will be a d mi nistere d as 
oral s us pe nsi o ns as escalati n g 
si n gle d oses t o be deter mi ne d
Partici pa nts will recei ve u p t o 4 
d oses of P F - 0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g place b o. 
D oses will be a d mi nistere d as 
oral s us pe nsi o ns as escalati n g 
si n gle d oses t o be determi ne d
Partici pa nts will recei ve u p t o 4 
d oses of P F - 0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g place b o. 
D oses will be a d mi nistere d as 
oral s us pe nsi o ns as escalati n g 
si n gle d oses t o be deter mi ne d
St atistic al Met h o ds :
T he sa m ple size has bee n c h ose n base d o n t he nee d t o mi ni mize first e x p os ure t o h u ma ns of 
a ne w c he mical e ntit y a n d t he re q uire me nt t o c o n d uct a de q uate safet y, t olerati o n, a n d P K 
assess me nts at eac h d ose le vel. All safet y a nal ys es will be perf or me d o n t he safet y a nal ysis 
set, w hic h is defi ne d as all partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d w h o ta ke 
at least 1 d ose of st u d y i nter ve nti o n. Partici pa nts will be a nalyz e d acc or di n g t o t he st u d y 
i nter ve nti o n t he y act ually recei ve d. 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. T he plas ma P K para meters f or 
P F ‑ 0 72 9 3 8 9 3 f oll o wi n g oral d ose a d mi nistrati o n will be deri ve d fr o m t he plas ma 
c o nce ntrati o n‑ti me pr ofiles. Plas ma P K para meters a n d c o nce ntrati o ns of P F- 0 7 2 9 3 8 9 3 will 
be descri pti vel y s u m marize d b y  d ose (f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) a n d 
n o mi nal ti me, as a p pr o priate.
Et hic al C o nsi der ati o ns:
T he partici pa nts i n t his st u d y  are n ot e x pecte d t o o btai n a n y s pecific be nefit be yo n d 
c o ntri b uti n g t o t he pr ocess of de vel o pi n g ne w t hera pies i n a n area of u n met nee d. T he y will 
recei ve cl ose m o nit ori n g of t heir safet y via st u d y pr oce d ures u n derta ke n (e g, p h ysical 
e xa mi nati o ns, ne ur ol o gical e xa mi nati o ns, 1 2 -lea d E C Gs, vital si g ns) w hic h will occ ur as 
o utli ne d i n t his pr ot oc ol. Base d o n t he t otalit y  of a vaila ble n o ncli nical data, a n d ta ki n g i nt o 
acc o u nt t he meas ures t o mi ni mize ris k t o st u d y  partici pa nts, t he o verall be nefit/ris k pr ofile 
s u p p orts cli nical testi n g of P F - 0 7 2 9 3 8 9 3 i n t his st u d y as part of t he cli nical de vel o p me nt f or 
a n i n dicati o n of heart fail ure wit h preser ve d ejecti o n fracti o n ( H F p E F ).
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 4
1. 2. Sc he m a
Fi g ure 1 St u d y Desi g n Sc he m a a, b,c
a.
D oses s h o w n f or eac h c o h ort e xce pt t he starti n g d ose i n C o h ort 1 are pla n ne d d oses a n d ma y be m o difie d base d o n 
e mer gi n g data fr o m pre vi o us c o h orts . Si milarl y, assi g n me nt t o st u d y i nter ve nti o n ma y be m o difie d. n re prese nts 
n u m ber of partici pa nts.
b.
S D D e xte m p ora ne o us pre p will be use d f or d ose escalati o n i n t his st u d y. P K  f or cr ystalli ne f or m ulati o n 
(faste d/fe d) ma y be st u die d i n re mai ni n g peri o ds of C o h ort 2 a n d/ or o pti o nal C o h ort 3 w he n it bec o mes a vaila ble .
c.
Preca uti o nar y se nti nel d osi n g will be use d i n a n y peri o d e val uati n g escalati n g d oses of P F - 0 7 2 9 3 8 9 3. F or s uc h 
peri o ds, 2 partici pa nts ( 1 recei v i n g P F -0 7 2 9 3 8 9 3 a n d 1 recei vi n g place b o) will be d ose d i nitiall y bef ore t he 
re mai ni n g partici pa nts of t hat peri o d are d ose d. Safet y a n d t olera bilit y data t hr o u g h at least 2 4 h o urs p ost -d ose f or 
t he se nti nel partici pa nts will be re vie we d pri or t o d osi n g t he re mai ni n g partici pa nts of t hat peri o d. Se nti nel d osi n g 
ma y be o mitte d w he n re peati n g a d ose le vel or a d mi nisteri n g a l o wer d ose le vel t ha n pre vi o usl y e val uate d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 5
1. 3. S c he d ule of Acti v ities
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures. Refer t o t he S T U D Y A S S E S S M E N T S A N D 
P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he 
pr ot oc ol. 
T he i n vesti gat or ma y  sc hed ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d in t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well -bei n g of t he partici pa nt .
T a ble 1 .
St u d y Sc he d ule of Assess me nt
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 t o Peri o d 4
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y - 1 D a y 1
D a y 2
D a y 3
D a y 4
Visit : 
D a y 8 ± 1
C o nt act:
D a y 
2 9- 3 6

All scree ni n g s h o ul d be d o ne ≤2 8 da ys bef ore t he first d ose. 

Da y relati ve t o start of st u d y i nter ve nti o n ( Da y 1).

Da y 1 acti vities at ti me = 0 h o urs are pri or t o t he d ose, 
e xce pt f or st u d y i nter ve nti o n a d mi nistrati o n.

O n -site f oll o w-u p visit t o occ ur o n Da y 8 ± 1 after t he fi nal 
d ose of st u d y i nter ve nti o n.

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 
2 8 t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
O ut patie nt visit
X
X
I nf or me d c o nse nt
X

I nf or me d c o nse nt s h o ul d 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. 3 f or 
a d diti o nal i nf or mati o n.
C R U c o nfi ne me nt
X
 
 
 

X

A d missi o n o n Da y -1 i n Peri o d 1 of eac h c o h ort. 
I ncl usi o n/e xcl usi o n criteria
X  
X

Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
Me dical/ me dicati o n hist or y
X  
X

Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
Hist or y of alc o h ol, t o bacc o, 
a n d ille gal dr u g use
X  
X

Peri o d 1 o nl y. Re vie w a n y c ha n ges fr o m Scree ni n g.
Re vie w c o nc o mita nt 
treat me nts
X
 
 
 
 
 
 

X  
X

See Secti o n 6. 9 f or a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 6
T a ble 1 .
St u d y Sc he d ule of Assess me nt
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 t o Peri o d 4
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y - 1 D a y 1
D a y 2
D a y 3
D a y 4
Visit : 
D a y 8 ± 1
C o nt act:
D a y 
2 9- 3 6

All scree ni n g s h o ul d be d o ne ≤2 8 da ys bef ore t he first d ose. 

Da y relati ve t o start of st u d y i nter ve nti o n ( Da y 1).

Da y 1 acti vities at ti me = 0 h o urs are pri or t o t he d ose, 
e xce pt f or st u d y i nter ve nti o n a d mi nistrati o n.

O n -site f oll o w-u p visit t o occ ur o n Da y 8 ± 1 after t he fi nal 
d ose of st u d y i nter ve nti o n.

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 
2 8 t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
P h ysical e xa m
X  
X
X
X  
X
X

C o m plete P E at scree ni n g or u p o n a d missi o n f or a 
partici pa nt’s first peri o d i n t he st u d y; ot her wise, brief P E , 
perf or me d f or fi n di n gs d uri n g pre vi o us e xa m or ne w/ o pe n 
A Es, at i n vesti gat or discreti o n.
I ncl u di n g hei g ht a n d wei g ht o nl y at scree ni n g.

See Secti o n 8. 3. 1 f or a d diti o nal i nf or mati o n.
Ne ur ol o gical e xa m
X
See 
Ta ble 2
X

D uri n g eac h peri o d. See Secti o n 8. 3. 2 f or a d diti o nal 
i nf or mati o n. 
De m o gra p h y
X
C o ntrace pti o n c hec k 
X  
X
X  
X  
X  
X

C o ntrace pti o n o nl y re q uire d f or male st u d y partici pa nts. 
C o ntrac epti ve g ui da nce is o utli ne d i n A p pe n di x 4 .
C O VI D -1 9 relate d meas ures 
X  
X  
X  
X  
X  
X  
X
X

Per C R U pr oce d ures
C R U disc har ge
X

Partici pa nts ma y be as ke d t o re mai n at t he C R U after 
c o m pleti o n of Da y 4 acti vities at t he discreti o n of t he 
i n vesti gat or or if safet y, t olera bilit y, or P K data dictate t he 
nee d t o pr ol o n g c o nfi ne me nt i n t he C R U
Seri o us a n d n o nseri o us A E 
m o nit ori n g
X
 
 
 
 
 
 

X  
X

See Secti o n 8. 4. 3 f or f oll o w-u p A E a n d S A E assess me nts.
1 2 -Lea d E C G
X
See 
Ta ble 2
X  
X  
X  
X  
X
X

Si n gle 1 2 -lea d E C G at scree ni n g, f oll o w-u p visit a n d E T. 
Tri plicate 1 2 -lea d E C Gs at all ot her ti mes. See Secti o n 
8. 3. 4 f or a d diti o nal details. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 7
T a ble 1 .
St u d y Sc he d ule of Assess me nt
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 t o Peri o d 4
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y - 1 D a y 1
D a y 2
D a y 3
D a y 4
Visit : 
D a y 8 ± 1
C o nt act:
D a y 
2 9- 3 6

All scree ni n g s h o ul d be d o ne ≤2 8 da ys bef ore t he first d ose. 

Da y relati ve t o start of st u d y i nter ve nti o n ( Da y 1).

Da y 1 acti vities at ti me = 0 h o urs are pri or t o t he d ose, 
e xce pt f or st u d y i nter ve nti o n a d mi nistrati o n.

O n -site f oll o w-u p visit t o occ ur o n Da y 8 ± 1 after t he fi nal 
d ose of st u d y i nter ve nti o n.

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 
2 8 t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
C o nti n u o us car diac tele metr y
X
See  Ta ble 2

Baseli ne tele metr y t o be rec or de d f or at least 2 h o urs pri or 
t o t he first d ose i n Peri o d 1 o nl y. T his ma y be d o ne 
i m me diatel y pri or t o d osi n g or at s o me 2-h o ur c o nti n u o us 
i nter val i n the 2 4 h o urs pri or t o d osi n g, as l o n g as t he 
partici pa nt is a wa ke. P ost - d ose tele metr y will c o nti n ue f or 
8 h o urs after d osi n g. See Secti o n 8. 3. 4. 1 f or a d diti o nal 
i nf or mati o n.
S u pi ne B P
X
X  
X  
X  
X  
X
X

Si n gle s u pi ne bl o o d press ure at scree ni n g, f oll o w -u p visit 
a n d E T. Tri plicate meas ures of s u pi ne bl o o d press ure at all 
ot her ti mes. See Secti o n 8. 3. 3 f or a d diti o nal i nf or mati o n. 
Te m perat ure, p ulse rate a n d 
res pirat or y rate 
X  
X  
X

See Secti o n 8. 3. 3 f or a d diti o nal i nf or mati o n.
St u d y i nter ve nti o n 
a d mi nistrati o n

Partici pa nts s h o ul d fast f or at least 1 0 h o urs pri or t o d osi n g, 
e xce pt f or peri o ds i n w hic h f o o d effects are i n vesti gate d. 
D osi n g u n der faste d or fe d c o n diti o ns is t o occ ur as 
o utli ne d i n Secti o n 5. 3. 2 . 
Sta n dar dize d meal/s nac k
X  
X  
X  
X  
X

See Secti o n 5. 3. 2 f or detaile d i nstr ucti o n.
Bl o o d s a m ples f or:
Safet y la b orat or y
X  
X 

X 
 

X 
X 

X 

Partici pa nt s h o ul d fast f or at least 4 h o urs pri or t o sa m ple 
c ollecti o n. Safet y la b orat or y i ncl u des he mat ol o g y, 
c he mistr y, a n d uri nal ysis, w hic h are liste d i n A p pe n di x 2 .
F S H
X
 
 



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.
HI V, H Bs A g, H Bs A b, 
H Bc A b, H C V A b 
X
 
 



See A p pe n di x 2: Cli nical La b orat or y Tests .
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 8
T a ble 1 .
St u d y Sc he d ule of Assess me nt
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 t o Peri o d 4
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y - 1 D a y 1
D a y 2
D a y 3
D a y 4
Visit : 
D a y 8 ± 1
C o nt act:
D a y 
2 9- 3 6

All scree ni n g s h o ul d be d o ne ≤2 8 da ys bef ore t he first d ose. 

Da y relati ve t o start of st u d y i nter ve nti o n ( Da y 1).

Da y 1 acti vities at ti me = 0 h o urs are pri or t o t he d ose, 
e xce pt f or st u d y i nter ve nti o n a d mi nistrati o n.

O n -site f oll o w-u p visit t o occ ur o n Da y 8 ± 1 after t he fi nal 
d ose of st u d y i nter ve nti o n.

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 
2 8 t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n. 
H o urs After D ose
0
2 4
3 6
4 8
7 2
Sa m ple f or s pecifie d ge netics 
X 
 



Sa m ples f or s pecifie d ge netics: C ollecte d i n Peri o d 1 o nl y.
If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at 
t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g 
c ollecte d i n c o nj u ncti o n wit h a partici pa nt visit. See Secti o n 
8. 6. 1 f or a d diti o nal details.
S a m ple f or s pecifie d pr otei n 
researc h 
See
Ta ble 2
 



T o be c ollecte d as o utli ne d i n Secti o n 8. 7. 2 .
P F- 0 7 2 9 3 8 9 3 P K
X  
X 
X 
X

X

See Secti o n 8. 5 f or a d diti o nal details.
S a m ple f or tra ns p orter 
bi o mar ker (s)
X


See Secti o n 8. 7. 5 f or a d diti o nal details.
Uri ne s a m ples f or:
Uri ne dr u g testi n g
X  
X


Res ults of a n y pre -d ose testi n g w ill be re vie we d a n d 
c o nfir me d acce pta ble pri or t o d osi n g.
Uri nal ysis ( wit h micr osc o p y, 
if nee de d)
X  
X
X
X  
X

X

Partici pa nt s h o ul d fast f or at least 4 h o urs pri or t o sa m ple 
c ollecti o n. Res ults of a n y pre-d ose testi n g will be re vie we d 
a n d c o nfir me d acce pta ble pri or t o d osi n g. See A p pe n di x 2: 
Cli nical La b orat or y Tests .
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 9
T a ble 2 .
St u d y Sc he d ule of Assess me nts f or P K, Vit als ,  E C Gs a n d Ot her o n D a y 1 of E ac h Peri o d
Visit I de ntifier 
N otes
St u d y D a y
1
H o urs After D ose
-1. 0
-0. 5
0
0. 5
1 
2 
3 
4 
6 
8
1 2 
1 4

H o ur 0 = pre d ose sa m ple c ollecti o n
Ne ur ol o gical e xa m
X
X

D uri n g eac h peri o d. See Secti o n 8. 3. 2 f or 
a d diti o nal i nf or mati o n. 
C o nti n u o us car diac tele metr y
X
 
 
 
 
 

X

Baseli ne tele metr y t o be rec or de d f or at 
least 2 h o urs pri or t o t he first d ose i n Peri o d 
1 o nl y. T his ma y be d o ne i m me diatel y pri or 
t o d osi n g or at s o me 2-h o ur c o nti n u o us 
i nter val i n t he 2 4 h o urs pri or t o d osi n g, as 
l o n g as t he partici pa nt is a wa ke. P ost-d ose 
tele metr y will c o nti n ue f or 8 h o urs after 
d osi n g. See Secti o n 8. 3. 4. 1 f or a d diti o nal 
i nf or mati o n.
Tri plicate 1 2 -Lea d E C G
X  
X  
X  
X 
X 
X 
X 
X 
X 
X  
X

Tri plicate meas ures are c ollecte d 
a p pr o xi matel y 2 - 4 mi n utes a part. See 
Secti o n 8. 3. 4 f or a d diti o nal details. 
Tri plicate S u pi ne B P
X  
X  
X  
X  
X  
X  
X  
X  
X

Tri plicate meas ures are c ollecte d 
a p pr o xi matel y 2 - 4 mi n utes a part. See 
Secti o n 8. 3. 3 f or a d diti o nal i nf or mati o n. 
Te m perat ure , p ulse rate a n d res pirat or y rate
X
X
X

See Secti o n 8. 3. 3 f or a d diti o nal 
i nf or mati o n.
St u d y i nter ve nti o n a d mi nistrati o n
X

Partici pa nts s h o ul d fast f or at least 1 0 h o urs 
pri or t o d osi n g, e xce pt f or peri o ds i n w hic h 
f o o d effects are i n vesti gate d. D osi n g u n der 
faste d or fe d c o n diti o ns is t o occ ur as 
o utli ne d i n Secti o n 5. 3. 2 .
Bl o o d s a m pli n g f or: 
P F -0 7 2 9 3 8 9 3 P K 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X

See Secti o n 8. 5 f or a d diti o nal details. 
Sa m ple f or s pecifie d pr otei n researc h 
X
X  
X
X

T o be c ollecte d as o utli ne d i n Secti o n 8. 7. 2 .
Sa m ple f or tra ns p orter bi o mar ker(s)
X  
X  
X  
X  
X  
X

See Secti o n 8. 7. 5 f or a d diti o nal details.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 0
2. I N T R O D U C TI O N
P F - 0 7 2 9 3 8 9 3 is an oral s mall m olec ule acti vat or of A M P K 3 t hat is c urre ntl y bei n g 
de vel o pe d f or t he treat me nt of H F p E F.
2. 1. St u d y R ati o n ale 
T his st u d y  will be t he first ti me P F - 0 7 2 9 3 8 9 3 is a d mi nistere d t o h u ma ns. T he p ur p ose of t he 
st u d y is t o e val uate t he safety, t olera bilit y , a n d plas ma P K of P F- 0 7 2 9 3 8 9 3 f oll o wi n g 
a d mi nistrati o n of escalati n g si n gle oral d oses t o healt h y a d ult partici pa nts.
2. 2. B ac k gr o u n d 
2. 2. 1. A M P K γ 3 a n d H F p E F
Heart fail ure re prese nts a gl o bal healt h c halle n ge wit h a n esti mate d pre vale nce of 3 0 milli o n 
i n di vi d uals affecte d w orl d wi de. M ore t ha n half of patie nts wit h heart fail ure ha ve heart 
fail ure wit h preser ve d ejecti o n fracti o n ( H F p E F).1 , 2 , 3 , 4 E xercise i nt olera nce is a ke y  feat ure 
of H F p E F a n d is a maj or s o urce of m or bi dit y f or t hese patie nts. T he g ol d sta n dar d meas ure 
of e xercise i nt olera nce is pea k o x y ge n c o ns u m pti o n ( pea k V O 2) meas ure d d uri n g a 
car di o p ul m o nar y e xercise test. T he pea k V O 2 f or H F p E F patie nts is ofte n bel o w esta blis he d 
t hres h ol ds t o s u p p ort i n de pe n de nt li vi n g. This decrease i n pea k V O 2 is sec o n dar y t o car diac
a n d peri p heral or ga n a b n or malities t hat res ult i n re d uce d o x y ge n deli ver y t o a n d/ or utilizati o n 
b y  e xercisi n g s keletal m uscle.5 , 6 Meta -a nal ys is of ra n d o mize d c o ntr ol e xercise i nter val trials 
i n s u bjects with H F p E F de m o nstrate d t hat e n d ura nce trai ni n g al o ne or w he n c o m bi ne d wit h 
resista nce trai ni n g is ass ociate d wit h c ha n ges i n s keletal m uscle bi o mar kers a n d a n effecti ve 
a p pr oac h t o i ncrease pea k V O 2.5 , 7 T hese fi n di n gs s u g gest t hat t hera pe utic strate gies t o 
e n ha nce s keletal m uscle f u ncti o n ma y be nefit H F p E F patie nts.
A M P K is t he se ns or of i ntracell ular e ner g y  a n d t he ce ntral re g ulat or of e ner g y h o me ostasis i n 
e u kar yo tes.8 A M P K is a heter otri meric c o m ple x c o nsisti n g of a si n gle catal ytic, 
scaff ol di n g, a n d re g ulat or y s u b u nit. T here are t w o is of or ms of t he a n d s u b u nits a n d 
t hree is of or ms of t he s u b u nit, gi vi n g rise t o t wel ve p ossi ble c o m bi nati o ns of t he A M P K 
heter otri meric c o m ple x. 9 A M P K ra pi dl y  res p o n ds t o c ha n ges i n cell ular A T P c o nce ntrati o ns 
w here t he rati o of A T P t o A M P or A D P c ha n ges t he acti vit y of A M P K, f urt her i nitiati n g 
m ulti ple pat h wa y s t o pr o m ote i ncrease d cata b olis m a n d decrease d a na b olis m, i ncl u di n g 
gl yc ol ys is, li pi d meta b olis m, a n d mit oc h o n drial h o me ostasis.1 0 , 1 1 , 1 2 , 1 3 , 1 4  
H u ma n s keletal m uscle (i ncl u di n g t he vast us lateralis) c o ntai ns t hree A M P K heter otri meric 
c o m ple xes: 2 2 1, 1 2 1 a n d 2 2 3, eac h c o ntri b uti n g t o ~ 6 5 %, ~ 1 5 % a n d ~ 2 0 % of t he 
t otal A M P K c o m ple x pr otei n p o ol i n t his tiss ue, res pecti vel y.1 5 , 1 6 T he 3 s u b u nit is 
e xcl usi vel y e x presse d i n s keletal m uscle, a n d t he 2 2 3 c o m ple x re prese nts t he maj or 
c o m ple x i n s keletal m uscle t hat is acti vate d d uri n g i nte nse e xercise .1 6 , 1 7 , 1 8 T he tiss ue -
s pecific e x pressi o n of t he is of or ms t he oretically c o ul d pr o vi de a mea ns t o selecti vel y 
acti vate a disti nct A M P K heter otri meric s pecies a n d p ote ntiall y  miti gate t he car di o vasc ular 
safety c o ncer ns descri be d f or -selecti ve a n d pa n- A M P K acti vat or s mall m olec ules.1 9 , 2 0
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 1
H u ma n carriers of t he rare 3 gai n of f u ncti o n varia nt, R 2 2 5 W, are ass ociate d wit h a n 
a p pr o xi mate d o u bli n g of b ot h basal a n d A M P -acti vate d A M P K acti vities i n differe ntiate d 
s keletal m uscle cells, a n d t he vast us lateralis m uscle o btai ne d fr o m t hese i n di vi d uals e x hi bits 
a ~ 90 % i ncrease i n gl yc o ge n c o nte nt a n d a ~ 3 0 % decrease i n i ntra m usc ular tri gl yceri des, 
p ossi bl y  as a c o nse q ue nce of i ncrease d fatty aci d beta -o xi dati o n d ue t o t he A M P K i n hi bit or y  
p h os p h or y lati o n of A C C.2 1 F urt her p he n ot y pi n g of t hese i n di vi d uals c o nfir me d t he i nitial 
fi n di n gs a n d de m o nstrate d t hat m yot u bes fr o m t he R 2 2 5 W carriers ha d t hreef ol d hi g her 
mit oc h o n drial c o nte nt a n d o xi dati ve ca pacit y , t o get her wit h i ncrease d glyc o ge n s y nt hesis 
rates vers us c o ntr ol m yot u bes. 2 2 A d diti o nall y , R 2 2 5 W carriers dis pla ye d a r e mar ka ble 
resista nce t o m usc ular fati g ue u p o n e xercise.2 2 T hese res ults s u p p ort t he h y p ot hesis t hat 
A M P K 3 acti vati o n i m pr o ves s keletal m uscle f u ncti o n.
Ta ke n t o get her, t hese data s u p p ort t he p ote ntial f or a selecti ve s mall m olec ule acti vat or of 
A M P Kγ 3 t o be nefit meta b olic H F p E F patie nts t hr o u g h a mec ha nis m t hat i ncreases pea k V O 2
a n d o verall s keletal m uscle f u ncti o n t o i m pr o ve e xercise i nt olera nce.
2. 2. 2. N o ncli nic al P h ar m ac ol o g y
P F -0 7 2 9 3 8 9 3 is a s mall m olec ule  acti vat or of A M P K w hic h selecti vel y bi n ds t o t he 
A M P K α 2 β 2γ 3 is of or m. B y  bi oc he mical assess me nt, P F-0 7 2 9 3 8 9 3 is a p ote nt a n d selecti ve 
γ 3 A M P K acti vat or w hic h i ncreases p h os p h or y lati o n of a n A C C-deri ve d C y s 5-S A M S 
pe pti de a gai nst h u ma n A M P K α 2 β 2γ 3 c o ntai ni n g c o m ple xes. Si milar p ote nc y was o bser ve d 
a gai nst m o use, d o g, a n d m o n ke y  A M P K α 2 β 2γ 3. I n A M P K α 2 β 2γ 3 tra nsie ntl y tra nsfecte d 
H E K 2 9 3 cells, P F - 0 7 2 9 3 8 9 3 i ncreases γ 3 ass ociate d p T hr 1 7 2.  
I n vi v o, after a si n gle P O dose, P F -0 7 2 9 3 8 9 3 de m o nstrate d d ose - a n d ti me-de pe n de nt 
c ha n ges i n s keletal m uscle bi o mar kers i ncl u di n g a n ele vati o n of t he rati o of 
 
( direct a n d d o w nstrea m tar gets of A M P K γ 3) i n gastr oc ne mi us 
m uscle of h u ma nize d A M P K 3 KI  DIO mice , a m o use m o del of H F p E F, c o m pare d wit h 
ve hicle . T he effect o n 
 was mai ntai ne d after re peate d dail y d osi n g wit h 
P F -0 7 2 9 3 8 9 3 f or 2 wee ks a n d t hese effects were de pe n de nt o n A M P Kγ 3, as P F- 0 7 2 9 3 8 9 3 
ha d n o si g nifica nt effect o n eit her e n d p oi nt i n A M P Kγ 3 K O DI O mice .
F urt her details of n o ncli nical p har mac ol o g y  are i ncl u de d i n t he I B.
2. 2. 3. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
T he n o ncli nical P K of P F -0 7 2 9 3 8 9 3 was c haracterize d b y  
i n m o use, rat, 
d o g, a n d m o n ke y , 
, a n d a t½ of a p pr o xi matel y   
 or s h orter acr oss 
s pecies. P F-0 7 2 9 3 8 9 3 e x hi bite d 
 oral bi oa vaila bilit y acr oss s pecies wit h 
bi oa vaila bilit y  i ncreasi n g  
 wit h use of t he S D D vers us cr ystalli ne f or m ulati o ns i n d o g 
a n d m o n ke y. I n re peat d ose t o xicit y st u dies i n mice a n d d o gs, sys te mic e x p os ure i ncrease d 
wit h i ncreasi n g d ose wit h mea n acc u m ulati o n rati os 
. Preli mi nar y assess me nt of 
P F -0 7 2 9 3 8 9 3 de m o nstrate d  
 passi ve per mea bilit y  a n d s u g geste d t hat P F- 0 7 2 9 3 8 9 3 is a 
s u bstrate f or 
 tra ns p orters. Re nal e xcreti o n of 
P F -0 7 2 9 3 8 9 3 was  
 i n rats, d o gs, a n d m o n ke y s (  
%) wit h t he maj or eli mi nati o n 
r o ute a p peari n g t o be meta b olic cleara nce.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 2
P F -0 7 2 9 3 8 9 3 was hi g hl y b o u n d t o m o use, d o g, a n d h u ma n plas ma pr otei ns a n d prefere ntiall y 
distri b ute d i nt o plas ma vers us re d bl o o d cells acr oss t he s pecies. F oll o wi n g S C d osi n g i n 
mice, P F -0 7 2 9 3 8 9 3 distri b ute d i nt o m uscle tiss ue.
F oll o wi n g i n vitr o a n d i n vi v o e val uati o n, t he pri mar y  cleara nce pat h wa y f or P F - 0 7 2 9 3 8 9 3 i n 
precli nical s pecies a n d h u ma ns a p pears
 
T here was o ne mi n or u ni q ue meta b olite (a 
 meta b olite) o bser ve d i n h u ma n he pat oc ytes a n d a n ot her mi n or u ni q ue meta b olite 
(
) t hat was o bser ve d o nl y i n micr o patter ne d 
c o-c ult ure d h u ma n he pat oc y tes.
At t he pre dicte d cli nical efficaci o us d ose, a p ote ntial D DI ( base d o n F D A a n d E M A D DI 
g ui da nce d oc u me nts usi n g t he mec ha ni stic m o dels) is pre dicte d f or P F-0 7 2 9 3 8 9 3 -me diate d 
. P F-0 7 2 9 3 8 9 3 als o has p ote ntial t o i n hi bit  
 
 I n a d diti o n, 
P F -0 7 2 9 3 8 9 3 has t he p ote ntial t o elicit i n d ucti o n of i ntesti nal  
 T here is a p ote ntial 
f or D DIs w hic h c o ul d occ ur wit h P F-0 7 2 9 3 8 9 3 as a victi m if c o -a d mi nistere d wit h m o derate 
a n d/ or p ote nt cli nical i n hi bit ors or i n d ucers of 
F urt her details of n o ncli nical P K a n d meta b olis m are i ncl u ded i n t he I B.
2. 2. 4. Bi o p h ar m ace utics
P F - 0 7 2 9 3 8 9 3 is a ne utral c o m p o u n d.  
 a n d a p pare nt per mea bilit y, as meas ure d i n 
cell li nes, i n dicate t hat t he m olec ule s h o ul d rea dil y  
 me m bra ne. T he 
s ol u bilit y of t he cr ystalli ne f or m will be  
 i n gastric fl ui d a n d i n t he i ntesti nal p H. Base d 
o n precli nical e x p os ure data a n d i n silic o m o delli n g, t he P F -0 7 2 9 3 8 9 3 cr y stalli ne f or m is 
e x pecte d t o be  
 a bs or be d u n der faste d c o n diti o n 
 m g, a n d 
 a bs or be d at t he d ose ra n ge 
 m g i n t he FI H st u d y usi n g a s us pe nsi o n 
f or m ulati o n. Base d o n p h ysi oc he mical pr o perties a n d i n silic o pre dicti o ns, f o o d is e x pecte d 
t o 
 e x p os ure of cr ystalli ne P F- 0 7 2 9 3 8 9 3.
A S D D is pre dicte d t o ha ve a n 
 P K pr ofile as c o m pare d t o t he cr ystalli ne f or m b y  
 e x p os ure o ver t he e ntire d ose ra n ge. T he s ol u bilit y of t he S D D will be  
 i n 
gastric fl ui d a n d i n t he i ntesti nal p H. P F -0 7 2 9 3 8 9 3 S D D is e x pecte d t o be  
 a bs or be d 
u n der faste d c o n diti o n at t he pre dicte d d osi n g r a n ge 
m g , a n d 
 a bs or be d at 
t he d o se ra n ge 
 m g i n t he FI H st u d y usi n g a s us pe nsi o n f or m ulati o n. 
Base d o n a vaila ble p h ys i oc he mical, precli nical P K a n d i n silic o oral a bs or pti o n data it is 
a ntici pate d t hat d ose li miti n g a bs or pti o n ma y occ ur i n t he d ose ra n ge 
 m g f or 
cr ys talli ne f or m a n d  
 m g f or S D D d ue t o s ol u bilit y  li mitati o ns. C o nse q ue ntl y, Cma x
a n d/ or A U C m a y  decrease at hi g her d oses. 
Data o n t h e h u ma n e x p os ure fr o m S D D vers us cr ystalli ne P F - 0 7 2 9 3 8 9 3 will be use d t o 
o pti mize t he perf or ma nce of t he dr u g pr o d uct.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 3
2. 2. 5. N o ncli nic al S afet y
P F -0 7 2 9 3 8 9 3 was e val uate d i n ge netic t o xicit y , safet y p har mac ol o g y, a n d re peat-d ose 
t o xicit y st u dies i n mice a n d d o gs. P F-0 7 2 9 3 8 9 3 is n ot m uta ge nic or clast o ge nic. A d verse 
m o nit ora ble cli nical si g ns (decrease d acti vit y , c o ol t o t o uc h, l o w b o d y te m perat ures, e mesis, 
tre m ors) a n d m ori b u n dit y were n ote d i n re peat-d ose t o xicit y  st u dies i n mice a n d/ or d o gs at 
d oses 
 m g/ k g/ da y. T he N O A E L was esta blis he d at 1 0 0 m g/ k g/ da y i n mice ( 2 3 da ys of 
c o nsec uti ve d osi n g) a n d d o gs ( 2 1 da y s of c o nsec uti ve d osi n g) (see Secti o n 4. 3. 3 f or e x p os ure 
data safet y  mar gi ns) a n d n o n-a d verse mi ni mal fi n di n gs were n ote d i n t he li ver (mi ni ma ll y
hi g her li ver wei g hts a n d A L T i n fe male mice) . I n t he si n gle-d ose safet y  p har mac ol o g y 
st u dies, m o nit ora ble a n d tra nsie nt car di o vasc ular ( decrease d B P, Q Tc, a n d c o m pe nsat or y 
i ncrease d H R i n d o gs), ner v o us ( decrease d l oc o m ot or acti vit y  i n mice), a n d res pirat or y 
( decrease d res pirat or y rate, mi n ute v ol u me a n d ti dal v ol u me i n mice) s yste ms effects were 
n ote d a n d t he N O E L was esta blis he d i n t hese st u dies.
I n s u m mar y, t he n o ncli nical safet y pr ofile of P F-0 7 2 9 3 8 9 3 has bee n a de q uatel y  c haracterize d 
a n d s u p p orts pr o gressi o n i nt o cli nical trials of u p t o 2 1 da y s. F urt her details of n o ncli nical 
safety are i ncl u de d i n t he I B.
2. 3. Be nefit/ Ris k Assess me nt
St u d y  C 5 1 7 1 0 0 1 is t he first ti me t hat P F -0 7 2 9 3 8 9 3 will be a d mi nistere d t o h u ma ns a n d is 
desi g ne d pri maril y t o ge nerate safet y, t olera bilit y , a n d P K data f or f urt her cli nical 
de vel o p me nt. F or healt h y  partici pa nts partici pati n g i n t his si n gle- d ose st u d y , n o cli nical 
be nefit is e x pecte d. T he p ur p ose of t he st u d y is t o pr o vi de t he basis f or f urt her cli nical 
de vel o p me nt of P F -0 7 2 9 3 8 9 3 as first-i n-class t hera p y f or treat me nt of patie nts wit h H F p E F .
As of t he date of fi nal pr ot oc ol, n o s pecific h u ma n ris ks ha ve bee n i de ntifie d; p ost ulate d ris ks 
base d o n n o ncli nical st u dies are s u m marize d i n Secti o n 2. 2. 5 . T he cli nic al i m pact of t hese 
p ote ntial ris ks will be mi ni mize d wit h preca uti o nar y se nti nel d osi n g a n d t hr o u g h t he 
pr o p ose d ca uti o us d ose -escalati o n pr ocess w herei n hi g her d oses of P F -0 7 2 9 3 8 9 3 will be 
a d mi nistere d o nl y after l o wer d oses ha ve bee n f o u n d t o be well t o lerate d wit h a n acce pta ble 
safety pr ofile. I n a d diti o n, t his st u d y will e m pl o y st o p pi n g r ules f or d ose escalati o n (Secti o n 
6. 6. 1 ) a n d i ncl u des sta n dar d, i nte nsi ve, i n patie nt m o nit ori n g of t he partici pa nt s f oll o wi n g 
a d mi nistrati o n of si n gle, oral d oses of t he st u d y i nter ve nti o n.
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 2 9 3 8 9 3 ma y  be f o u n d i n t he I B, w hic h is t he S R S D f or t his st u d y. 
Refer t o t he St u d y  Inter ve nti o n(s) ta ble i n Secti o n 6. 1 f or a c o m plete descri pti o n of S R S Ds.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 4
2. 3. 1. Ris k Assess me nt
P ote nti al Ris k of Cli nic al Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n(s) P F -0 7 2 9 3 8 9 3
Car di o vasc ular , ne ur ol o gic a n d p ul m o nar y si g ns 
a n d s y m pt o ms
Tra nsie nt c li nical si g ns of car di o vasc ular
(decrease d B P, Q Tc, a n d c o m pe nsat or y i ncrease d 
H R) , C N S (decrease d l oc o m ot or acti vit y ) a n d 
p ul m o nar y effects (decrease d res pirat or y rate, 
mi n ute v ol u me a n d ti dal v ol u me ) were n ote d i n t he 
n o n- cli nical si n gle-d ose t o xicit y st u dies. Refer t o 
Secti o n 2. 2. 5 f or a d diti o nal details.
Car diac , p ul m o nar y a n d ne ur ol o gic m o nit ori n g 
i ncl u di n g tele metr y, electr ocar di o gra ms, vital 
si g ns, res pirat or y rate a n d f ull ne ur ol o gic e xa ms
will be i nc or p orate d as part of safet y m o nit ori n g . 
Preca uti o nar y se nti nel d osi n g will als o be use d i n 
t his st u d y. 
Dr u g -dr u g i nteracti o ns res ulti n g i n e x p os ure 
c ha n ges t o bac k gr o u n d c o nc o mita nt me dicati o ns
Base d o n re g ulat or y m o dels, P F -0 7 2 9 3 8 9 3 has t he 
p ote ntial t o 
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d 
dietar y a n d her bal s u p ple me nts are pr o hi bite d 
wit hi n 7 da ys or 5 half -li ves ( whic he ver is l o n ger) 
pri or t o t he first d ose of st u d y i nter ve nti o n 
t hr o u g h t he last P K c ollecti o n.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 5
2. 3. 2. Be nefit Assess me nt
T he partici pa nts i n t his st u d y  are n ot e x pecte d t o o btai n a n y s pecific be nefit be yo n d 
c o ntri b uti n g t o t he pr oces s of de vel o pi n g a ne w t hera p y f or patie nts wit h H F p E F a n area wit h
u n met nee d. T he y  will recei ve cl ose m o nit ori n g of t heir safety via st u d y pr oce d ures 
u n derta ke n (e g, p h ys ical e xa mi nati o ns, ne ur ol o gical e xa mi nati o ns, 1 2- lea d E C Gs, vital 
si g ns) w hic h will occ ur as o utli ne d i n t his pr ot oc ol.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
Base d o n t he t otalit y  of a vaila ble n o ncli nical data, a n d ta ki n g i nt o acc o u nt t he meas ures t o 
mi ni mize ris k t o st u d y  partici pa nts, t he o verall be nefit/ris k pr ofile s u p p orts cli nical testi n g of 
P F -0 7 2 9 3 8 9 3 i n t his st u d y  as part of t he cli nical de vel o p me nt f or a n i n dicati o n of H F p E F.
3. O B J E C TI V E S A N D E N D P O I N T S
O bjecti ves
E n d p oi nts
Pri m ar y : 
Pri m ar y : 

T o e val uate t he safet y a n d t olera bilit y of si n gle 
asce n di n g d oses of P F - 0 7 2 9 3 8 9 3 a d mi nistere d orall y 
t o healt h y a d ult partici pa nts.

Assess me nt of a d verse e ve nts, cli nical safet y la b orat or y 
tests, vital si g ns, c o nti n u o us car diac m o nit ori n g, 1 2-lea d 
electr ocar di o gra ms, p h ysical e xa mi nati o ns a n d 
ne ur ol o gical e xa mi nati o ns .
Sec o n d ar y:
Sec o n d ar y : 

T o e val uate t he P K of P F -0 7 2 9 3 8 9 3 f oll o wi n g si n gle 
d oses of P F -0 7 2 9 3 8 9 3 a d mi nistere d orall y t o healt h y 
a d ult partici pa nts.

P K para meters deri ve d fr o m plas ma P F -0 7 2 9 3 8 9 3 
c o nce ntrati o ns: C ma x , T ma x , A U C last, a n d if data per mit, 
A U C i nf, a n d t½ .
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y: 

T o e val uate a d diti o nal P K para meters of P F -0 7 2 9 3 8 9 3 
f oll o wi n g si n gle d oses of P F- 0 7 2 9 3 8 9 3 a d mi nistere d 
orall y t o healt h y a d ult partici pa nts.

A d diti o nal P K para meters deri ve d fr o m plas ma 
P F - 0 7 2 9 3 8 9 3 c o nce ntrati o ns: Cma x( d n), A U C last( d n) a n d 
if data per mit, A U C i nf( d n), C L/ F a n d V z/ F .

T o e val uate t he P K of P F -0 7 2 9 3 8 9 3 f oll o wi n g si n gle 
d ose(s) of a cr ystalli ne f or m of P F -0 7 2 9 3 8 9 3 i n faste d 
a n d/ or fe d state, if c o n d ucte d. 

P K para meters deri ve d fr o m plas ma P F -0 7 2 9 3 8 9 3 
c o nce ntrati o ns: C ma x, T ma x , A U C last, a n d if data per mit, 
A U C i nf, a n d t½ .

T o e val uate t he effects of si n gle asce n di n g d oses of 
P F -0 7 2 9 3 8 9 3 o n bi o mar ker (s) of  tra ns p orter acti vit y, 
if fe asi ble & a n alyze d .

F or eac h bi o mar ker (as a p plica ble): A U C 2 4 a n d C ma x
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a ra n d o mize d, i n vesti gat or - a n d partici pa nt -bli n d, s p o ns or -o pe n, place b o -c o ntr olle d, 
first-i n-h u ma n, si n gle asce n di n g oral d ose, 4 -peri o d, cr oss o ver st u d y  of P F- 0 7 2 9 3 8 9 3
a d mi nistere d t o healt h y a d ult partici pa nts. A p pr o xi matel y 2 4 healt h y a d ult partici pa nts ( u p t o 
3 c o h orts of a p pr o xi matel y  8 partici pa nts eac h) will be e nr olle d i n t his st u d y. T he first 2 
c o h orts are pla n ne d, a n d t he t hir d c o h ort is o pti o nal. I n eac h peri o d , partici pa nts will be 
ra n d o mize d t o eit her P F- 07 2 9 3 8 9 3 or place b o i n a rati o of 3: 1. Eac h partici pa nt is pla n ne d t o 
u n der g o u p t o 4 treat me nt peri o ds recei vi n g u p t o 4 d oses of P F- 0 7 2 9 3 8 9 3 a n d u p t o 2 d oses 
of place b o.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 6
Preca uti o nar y  se nti nel d osi n g will be use d i n a n y peri o d e val uati n g escalati n g d oses of 
P F - 0 7 2 93 8 9 3 a n d ma y be o mitte d f or peri o ds w he n re peati n g a d ose le vel or a d mi nisteri n g a 
l o wer d ose le vel t ha n pre vi o usl y e val uate d. F or peri o ds wit h se nti nel d osi n g, t w o partici pa nts 
( 1 recei vi n g P F- 0 72 9 3 8 9 3 a n d 1 recei vi n g place b o) will be d ose d i nitiall y  bef ore t he 
re mai ni n g partici pa nts of t hat peri o d are d ose d. Safet y a n d t olera bilit y data t hr o u g h at least 
2 4 h o urs p ost - d ose f or t he se nti nel partici pa nts will be re vie we d pri or t o d osi n g t he 
re mai ni ng partici pa nts of t hat peri o d. D ose le vels will be escalate d t o brac ket t he e x pecte d 
cli nical d ose ra n ge, b ut t he pr ojecte d e x p os ures will n ot e xcee d t he pre defi ne d h u ma n 
e x p os ure li mits.
Scree ni n g acti vities will be c o m plete d o ver t he 2 8 da y s pri or t o ra nd o mizati o n i n Peri o d 1. 
Partici pa nts c o nfir mi n g eli gi bilit y  acc or di n g t o Secti o n 5 will be a d mitte d t o t he C R U o n 
D a y -1 i n Peri o d 1 f or eac h c o h ort. F or eac h peri o d i n t his st u d y , o n Da y 1, f oll o wi n g 
≥1 0 h o ur o ver ni g ht fast, partici pa nts will recei ve a si n gle oral d ose of P F - 0 7 2 9 3 8 9 3 or 
place b o. Partici pa nts will be disc har ge d o n Da y 4 , f oll o wi n g c o m pleti o n of all sc he d ule d 
assess ments (a p pr o xi matel y 7 2 h o urs p ost -d ose ). Partici pa nts ma y  be as ke d t o re mai n i n t he 
C R U after c o m pleti o n of Da y  4 acti vities at t he discreti o n of t he i n vesti gat or or if safet y , 
t olera bilit y, or P K data dictate t he nee d t o pr ol o n g c o nfi ne me nt i n t he C R U. In eac h c o h ort, a 
was h o ut i nter val of at least 7 da y s will be i ntr o d uce d bet wee n s u bse q ue nt d oses. D uri n g t he 
was h o ut i nter val, e mer gi n g 2 4 -h o ur P K a n d 7 2 -h o ur safet y data will be re vie we d a n d t he 
ne xt d ose will be deter mi ne d. A n o n -site f oll o w-u p visit will occ ur o n Da y 8 ± 1 after t he fi nal 
d ose . T he f oll o w-u p c o ntact ma y  occ ur via tele p h o ne c o ntact a n d m ust occ ur 2 8-3 5 da y s 
after a d mi nistrati o n of t he fi nal d ose of st u d y i nter ve nti o n. 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 tele p h o ne f oll o w -u p c o ntact will be 
a p pr o xi matel y 1 4 wee ks.
Base d o n t he re vie w of e mer gi n g safet y, t olera bilit y, a n d P K data i n C o h orts 1 a n d 2, t he
re mai ni n g peri o ds of C o h ort 2 a n d/ or a n o pti o nal t hir d c o h ort e nr oll i n g a p pr o xi matel y 
8 partici pa nts (cr oss o ver, place b o c o ntr olle d desi g n) ma y  be use d t o e x pl ore a d diti o nal d oses, 
t o re peat a d ose, or t o e val uate effect of cr ystalli ne f or m o n P F - 0 7 2 9 3 8 9 3 P K i n faste d a n d/ or 
fe d state.  
D osi n g will occ ur i n t he faste d state f or all peri o ds, e xce pt if a n o pti o nal e x pl orat or y  
assess me nt of t he effect of f o o d o n cr ys talli ne P F -0 7 2 9 3 8 9 3 P K is c o n d ucte d. T he act ual 
d ose le vel f or t he assess me nt of f o o d effect will be selecte d base d o n e mer gi n g safet y, 
t olera bilit y, a n d P K data b ut will be e x pecte d t o ac hie ve pr ojecte d t hera pe utic e x p os ures 
(Secti o n 4. 3. 2 ).
If a partici pa nt dr o ps o ut bef ore c o m pleti n g all st u d y peri o ds wit hi n a c o h ort, or wit h dra ws 
f or a reas o n u nrelate d t o safety, t he partici pa nt ma y be re place d at t he discreti o n of t he 
i n vesti gat or a n d s p o ns or. T he re place me nt partici pa nt(s) ma y or ma y n ot be re q uire d t o 
c o m plete all peri o ds of t he c o h ort i n w hic h t he y  are partici pati n g at t he discreti o n of t he 
i n vesti gat or a n d s p o ns or.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 7
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T he p o p ulati o n pla n ne d f or t his st u d y  will be healt h y male a n d fe male partici pa nts. Fe male 
partici pa nts will be c o nfir me d t o be of n o n -c hil d beari n g p ote ntial, si nce at t he prese nt ti me 
e m br yo -fetal de vel o p me ntal t o xicit y st u dies wit h P F- 0 7 2 9 3 8 9 3 ha ve n ot bee n c o n d ucte d. I n 
male partici pa nts, a p pr o priate meas ures are e x pecte d t o be f oll o we d t o mi ni mize p ote ntial 
tra nsfer of P F-0 7 2 9 3 8 9 3 via se me n t o part ners (see A p pe n di x 4 ).
Gi ve n t his is t he first ti me P F -0 7 2 9 3 8 9 3 will be a d mi nistere d t o h u ma ns, a n escalati n g si n gle 
oral d ose cr oss o ver desi g n wit h caref ul assess me nt a n d o n g oi n g re vie w of safet y, t olera bilit y  
a n d P K data of P F -0 7 2 9 3 8 9 3 is pla n ne d. D ue t o t he fi n di n gs of tra nsie nt cli nical si g ns of 
cardi o vasc ular a n d ne ur o p ul m o nar y  effects i n t he n o n-cli nical c hr o nic t o xic ol o g y st u dies, 
ne ur ol o gical e xa mi nati o n, R R a n d b o d y  te m perat ure meas ure me nt will be perf or me d   i n t his 
st u d y. I n a d diti o n, a preca uti o nar y  se nti nel d osi n g will be use d . T he hi g hest a ntici pate d C ma x 
a n d A U C 2 4 of P F -0 7 2 9 3 8 9 3 will n ot e xcee d t he pre -defi ne d h u ma n e x p os ure st o p pi n g li mits . 
F urt her m ore, to per mit a n u n biase d assess me nt of safet y, t he partici pa nts’ treat me nt 
assi g n me nts (acti ve treat me nt vers us place b o) will be bli n de d t o b ot h site staff (e xce pt t h ose 
i n v ol ve d i n pre parati o n of d oses) as well as t he st u d y partici pa nts. H o we ver, t o per mit 
real-ti me re vie w of t he safet y a n d P K data, a li mite d n u m ber of s p o ns or st u d y tea m me m bers 
will be u n bli n de d (see Secti o n 6. 4. 3 ).
I n eac h peri o d, a p pr o xi matel y 6 partici pa nts are pla n ne d t o recei ve P F -0 7 2 9 3 8 9 3, a n d 
2 partici pa nts are pla n ne d t o recei ve place b o. T he 4 -peri o d cr oss o ver desi g n will per mit b ot h 
wit hi n a n d bet wee n partici pa nt assess me nt of safet y /t olera bilit y a n d P K at m ulti ple d ose 
le vels a n d place b o. A n a d diti o nal c o h ort ma y  be i ncl u de d if, base d o n e mer gi n g data fr o m 
t he first 2 c o h orts, it is dee me d necessar y t o meet t he o bjecti ves of t his st u d y . F or a gi ve n 
partici pa nt, d osi n g will be se parate d b y at least 7 da y s. T his pla n ne d d osi n g i nter val is 
dee me d s ufficie nt base d o n t he pr ojecte d P F -0 7 2 9 3 8 9 3 ter mi nal half -life (see Secti o n 4. 3. 1 ).
Base d o n t he pre dicte d t ½ of P F -0 7 2 9 3 8 9 3, plas ma c o nce ntrati o ns of P F -0 7 2 9 3 8 9 3 are 
e x pecte d t o be bel o w t he li mit of detecti o n i n a p pr o xi matel y  
, t h us P K sa m ples are 
pla n ne d t o be c ollecte d o ver 
 h o urs p ost- d ose. H o we ver, sa m pli n g ti mes, d urati o n of 
sa m pli n g, a n d/ or t he le n gt h of t he i nter val bet wee n d oses ma y be m o difie d a n d/ or e xte n de d 
base d o n e mer gi n g P K. T he pla n ne d d oses i n t he d ose escalati o n se q ue nce ( Ta ble 3 ) ma y be 
m o difie d or re peate d, as g ui de d b y e mer gi n g safet y, t olera bilit y, a n d P K data b ut will f oll o w 
t he d ose-escalati o n r ules defi ne d i n Secti o n 6. 6. 1 .
Base d o n precli nical e x p os ure data a n d i n silic o m o delli n g, t he P F -0 7 2 9 3 8 9 3 cr y stalli ne f or m 
is e x pecte d t o be 
 a bs or be d u n der faste d c o n diti o n 
 m g, 
a n d 
 a bs or be d at t he d ose ra n ge 
 m g. T heref ore, S D D f or m ulati o n wit h hi g her 
s ol u bilit y a n d hi g her pre dicte d e x p os ures as c o m pare d t o t he cr ystalli ne f or m, will be use d i n 
t his st u d y.
Base d o n p h ys i oc he mical pr o perties a n d i n silic o pre dicti o ns, f o o d is e x pecte d t o ha ve a 
 i m pact o n cr ystalli ne P F-0 7 2 9 3 8 9 3 e x p os ure . An e x pl orat or y  assess me nt of t he P K 
of cr ys talli ne P F - 0 7 2 93 8 9 3 wit h or wit h o ut f o o d relati ve t o S D D f or m ulati o n ma y  be 
c o n d ucte d. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 8
I n vitr o data i n dicate d t hat P F- 0 7 2 9 3 8 9 3 has t he p ote ntial t o i n hi bit 
 
 i n h u ma ns. I n t his st u d y, bl o o d sa m ples f or tra ns p orter bi o mar kers 
(e g,
) will be c ollecte d t o e val uate p ote ntial effects of P F - 0 7 2 9 3 8 9 3 o n tra ns p orter 
acti vit y i n h u ma n. H o we ver, t hese sa m ples will o nl y be a nalyz e d if feasi ble a n d dee me d 
necessar y . 
T he sa m ples will be c ollecte d f or e x pl orat or y  a nal ysis of circ ulat or y bi o mar kers of A M P Kγ 3 
acti vati o n. T he serial bl o o d sa m ples will be c ollecte d t o u n dersta n d t he ti me-de pe n de nt 
pr ofile of circ ulat or y  bi o mar ker c ha n ges f oll o wi n g P F - 0 7 2 9 3 8 9 3 treat me nt, a n d p ossi bl y  t o 
i de ntif y t he ti mep oi nt c orres p o n di n g t o pea k. T he res ults of t hese a nal y ses will n ot be 
re p orte d i n t he C S R. 
C o nsi deri n g t he n o ncli nical safet y  st u dies wit h P F-0 7 2 9 3 8 9 3 i n mice a n d d o gs (see 
Secti o n 2. 2. 3 ), t he sta n dar d safety assess me nts use d b y  t he s p o ns or i n trials a d mi nisteri n g 
i n vesti gati o nal pr o d uct f or t he first ti me t o h u ma ns are dee me d s uita ble (see A p pe n di x 2 ).
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts 
H u ma n re pr o d ucti ve safet y  data are li mite d f or P F - 0 7 2 9 3 8 9 3. T heref ore, t he use of a hi g hl y 
effecti ve met h o d of c o ntrace pti o n is re q uire d f or male partici pa nts (see A p pe n di x 4 ). Fe male 
partici pa nts of c hil d beari n g p ote ntial are e xcl u de d fr o m partici pati o n i n t he trial. 
T here is n o s us pici o n of h u ma n terat o ge nicit y base d o n t he i nte n de d p har mac ol o g y  of t he 
c o m p o u n d.
4. 3. J ustific ati o n f or D ose
T he pr o p ose d d ose le vels of P F -0 7 2 9 3 8 9 3 were deri ve d base d o n c u m ulati ve n o ncli nical 
data, i ncl u di n g i n vitr o, i n vi v o, P K a n d P D data, a n d t he c o m plete d n o ncli nical t o xicit y  
st u dies. D ose le vels ha ve bee n selecte d t o brac ket t he e x pecte d cli nical d ose a n d e x p os ure 
ra n ge, w hile c o nsi deri n g u ncertai nty i n t he pr ojecte d cli nicall y efficaci o us d ose. D ose le vels 
be y o n d t he starti n g d ose (i n Peri o d 1 of C o h ort 1) ma y  be m o difie d base d o n e mer gi n g 
h u ma n safet y, t o lera bilit y, a n d P K data i n t he c urre nt st u d y.
4. 3. 1. Pre dicti o n of H u m a n P K
T he h u ma n P K pr ofile was pre dicte d usi n g h u ma n he pat oc y tes a n d n o n-cli nical data. 
P F -0 7 2 9 3 8 9 3 is pre dicte d t o 
 
 
4. 3. 2. Pre dicti o n of Effic aci o us D ose / C o nce ntr ati o n 
T he P K /P D of P F -0 7 2 9 3 8 9 3 was e xa mi ne d usi n g a P K/ P D - h KI m o use m o del assessi n g t he 
res p o nse of  
 i n m uscle tiss ue as a bi o mar ker. Base d o n t he pre dicte d h u ma n P K, t he 
pr ojecte d h u ma n efficaci o us d ose of P F- 0 7 2 9 3 8 9 3 is 
. T his d ose is e x pecte d t o 
ac hie ve 
 acti vati o n of A M P K3 a n d res ult i n a stea d y state t otal C ma x of 
, a n d a t otal A U C2 4 of 
 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 2 9
4. 3. 3. H u m a n E x p os ure St o p pi n g Li mits
T he N O A E L i n t he 1 m o nt h G L P t o xicit y  st u dy i n mice (t he m ost se nsiti ve s pecies) was
1 0 0 m g/ k g/ da y  (
). T heref ore, 
t he m o use N O A E L e x p os ures are use d t o set h u ma n e x p os ure li mits f or P F- 0 7 2 9 3 8 9 3.
After c orrecti n g f or s pecies - de pe n de nt, plas ma pr otei n bi n di n g bet wee n m o use a n d h u ma n
(fu, p of
res pecti vely):

T he h u ma n P F -0 7 2 9 3 8 9 3 C ma x li mit is a t otal Cma x of 
 n g/ m L (
 n g/ m L
u n b o u n d).

T he h u ma n P F - 0 7 2 9 3 8 9 3 A U C 2 4 li mit is a t otal A U C2 4 of 
 n g• h/ m L 
(
n g• h/ m L u n b o u n d).
4. 3. 4. R ati o n ale f or D ose Selecti o n 
T he safet y, t olera bilit y , a n d plas ma P K of P F- 0 7 29 3 8 9 3 after a d mi nistrati o n of si n gle 
escalati n g oral d oses acr oss a wi de d ose/e x p os ure ra n ge will be e val uat e d i n t his st u d y. T he 
d oses prese nte d i n Ta ble 3 are pr ojecte d base d o n n o ncli nical data a n d ma y be m o difie d 
base d o n e mer gi n g o bser ve d h u ma n safet y , t olera bilit y, a nd P K data ge nerate d d uri n g t his 
st u d y. T he i nitial ra n ge of pla n ne d d oses i n t his st u d y were esta blis he d usi n g t o xic o ki netic 
data, pre dicte d h u ma n P K para meter esti mates, a n d pr ojecte d efficaci o us c o nce ntrati o ns.
T a ble 3.
Pre dicte d H u m a n E x p os ures a n d S afet y M ar gi ns at Pr o p ose d Si n gle 
D oses of P F -0 7 2 9 3 8 9 3
D ose ( m g)
Pr ojecte d E x p os ures a
Safet y Mar gi ns b
C ma x ( n g/ m L)
A U C 2 4
( n g•h/ m L)
C ma x
A U C 2 4
1 0
5 7. 9
6 7 1
2 3 3
2 3 2
3 0
1 7 4
2 0 1 2
7 7. 6
7 7. 3
1 0 0
5 7 9
6 7 0 8
2 3. 3
2 3. 2
3 0 0
1 7 3 7
2 0 1 2 0
7. 7 6
7. 7 3
7 5 0
4 3 4 2
5 0 3 1 0
3. 1
3. 0 9
1 5 0 0
8 6 8 4
1 0 0 6 0 0
1. 5 5
1. 5 5
a.
H u ma n P K pr ofiles were pre dicte d usi n g a 1 -c o mpart me nt m o del w it h t he pr ojecte d h u ma n P K 
para meters f or P F -0 7 2 9 3 8 9 3 . T he m o del ass u mes li near P K at all d oses 
 
b.
S afet y mar gi ns calc ulate d usi n g t he t otal e x p os ure li mits i n h u ma n w hic h was base d o n u n b o u n d C ma x
( 
 n g/ m L) a n d u n b o u n d A U C2 4 ( 
 n g•h/ m L) o bser ve d at N O A E L ( 1 0 0 m g/ k g) i n 1 -m G L P 
t o xic ol o g y st u d y i n m o use, t he m ost se nsiti ve s pecies a n d c orrecte d wit h h u ma n pr otei n bi n di n g (fu , p
=
) 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 0
T he P F -0 7 2 9 3 8 9 3 starti n g d ose le vel of 1 0 m g is pla n ne d. T he pre dicte d P F - 0 7 2 9 3 8 9 3 Cma x
a n d A U C 2 4 after si n gle d ose of 1 0 m g are a p pr o xi matel y  2 3 3- a n d 2 3 2- f ol d, res pecti vely, 
bel o w t he e x p os ure li mit defi ne d f or P F -0 7 2 9 3 8 9 3 d ose escalati o n i n Secti o n 4. 3. 3 . T he 
ma xi m u m tar get c o vera ge f ollo wi n g a si n gle 1 0 m g d ose is pre dicte d t o be 
% wit h 
ma xi m u m i ncrease i n 
. T he pre dicte d P F -0 7 2 9 3 8 9 3 e x p os ures ( Cma x
a n d A U C 2 4) after si n gle d ose of 1 0 m g are a p pr o xi matel y 
 l o wer t ha n pre dicte d 
e x p os ures at pr ojecte d h u m a n efficaci o us d ose. A si n gle d ose of 1 5 0 0 m g (t he t o p d ose i n 
Ta ble 3 ) is esti mate d t o pr o vi de a n e x p os ure mar gi n of 
f or b ot h C ma x a n d A U C 2 4 
relati ve t o t he e x p os ure li mits.
T he d ose ra n ge t o be st u die d was selecte d t o acc o u nt f or u ncertai nties i n t he pr ojecte d C eff
a n d t he pr ojecte d t hera pe utic d ose, w hile als o brac keti n g t he e x pecte d cli nicall y  effecti ve 
d ose ra n ge i n h u ma ns f or cli nicall y  rele va nt p har mac olo gical acti vit y a n d pr o vi di n g safet y 
c o vera ge f or a wi de ra n ge of P F- 0 7 2 9 3 8 9 3 d oses.
Assess me nt of t he safet y,  t olera bilit y, a n d P K after eac h si n gle d ose le vel will be c o n d ucte d 
bef ore escalati n g t o t he ne xt d ose le vel. T he d ose/e x p os ure- escalati o n i ncre m e nts are pla n ne d 
t o be u p t o a p pr o xi matel y se mi-l o garit h mic i ncreases i n e x p os ure fr o m t he pre vi o us hi g hest 
d ose le vel t hat has bee n e val uate d. If e x p os ure e xcee ds t he pr ojecte d t hera pe utic ra n ge, or if 
c ha n ges i n safet y para meters are o bser ve d, s maller d o se-escalati o n ste ps ma y be 
i m ple me nte d.
T he act ual d ose le vels, tar get e x p os ures, a n d/ or d ose le vel i ncre me nts ma y  be a dj uste d 
( hi g her or l o wer) d uri n g t he st u d y base d o n e mer gi n g h u ma n safety, t olera bilit y , a n d P K 
data, b ut pr ojecte d e x p os ures will n ot e x cee d t he pre defi ne d h u ma n e x p os ure li mits. D ose 
le vels ma y als o be re peate d if warra nte d.
W he n t he assess me nt of t he f o o d effect f or t he cr ystalli ne f or m o n t he P K of P F- 0 7 2 9 3 8 9 3 is 
c o n d ucte d, t he d ose le vel(s) will be selecte d base d o n t he e mer gi n g safety , t olera bilit y, a n d 
P K data fr o m pre vi o us peri o ds of t he st u d y. T he act ual d ose le vel(s) will be e x pecte d t o 
ac hie ve e x p os ures si milar t o or greater t ha n pr ojecte d t hera pe utic e x p os ures (as o utli ne d i n 
Secti o n 4. 3. 2 ), b ut t he pr ojecte d e x p os ures will n ot e xcee d t he pre defi ne d h u ma n e x p os ure 
li mits (as o utli ne d i n Secti o n 4. 3. 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 par tici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y if t he y ha ve c o m plete d all peri o ds of 
t he st u d y, i ncl u di n g t he last sc he d ule d pr oce d ure s h o w n i n t he S o A .
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate p artici pa nt s are e nr olle d, i ncl u di n g 
partici pa nts acr oss di verse a n d re prese ntati ve racial a n d et h nic bac k gr o u n ds. If a 
prescree ni n g t o ol is utilize d f or st u d y recr uit me nt p ur p oses, it will i ncl u de c ollecti o n of 
i nf or mati o n t hat reflects t he e nr oll me nt of a di verse partici pa nt p o p ulati o n i ncl u di n g, w here 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 1
per mitte d u n der l ocal re g ulati o ns, a ge, se x, race, a n d et h nicit y . T he f oll o wi n g eli gi bilit y  
criteria are desi g ne d t o select partici pa nt s f or w h o m partici pati o n i n t he st u d y  is c o nsi dere d 
a p pr o priate. All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het her a partic ular part ici 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 ply:
A ge a n d Se x :
1.
Fe male s of n o n -c hil d beari n g p ote ntial a n d males 1 8 t o 6 5 ye ars of a ge, i ncl usi ve, at 
t he ti me of si g ni n g t he I C D w h o are o vertl y healt h y as deter mi ne d b y me dical 
e val uati o n i ncl u di n g me dical hist or y, p h ysical e xa mi nati o n, la b orat or y tests, a n d 
car diac m o nit ori n g.

Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d 
fe male (Secti o n 1 0. 4. 2 ) partici pa nts.
Ot her I ncl usi o n Criteri a :.
2.
B MI of 1 6 - 3 0. 5 k g/ m 2; a n d a t otal b o d y wei g ht > 5 0 k g ( 1 1 0 l b).
3.
W illi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt pla n, la b orat or y tests, 
lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1 , w hic h 
i ncl u des c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he IC D a n d i n 
t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 2

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.
2.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y or ot her c o n diti o ns or sit uati o ns 
relate d t o C O VI D-1 9 pa n de mic t hat ma y i ncrease t he ris k of st u d y partici pati o n or, i n 
t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
3.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n, wit h t he 
 
w hic h are pr o hi bite d wit hi n 1 4 da y s pl us 5 half-li ves pri or t o t he first d ose of st u d y 
i nter ve nti o n. Refer t o Secti o n 6. 9 Pri or a n d C o nc o mita nt T hera p y f or a d diti o nal 
details.
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
4.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y i nter ve nti o n use d i n t his st u d y  ( w hic he ver is l o n ger). Partici pati o n i n 
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d ur i n g t heir 
partici pati o n i n t his st u d y .
Di a g n ostic Assess me nts:
5.
A p ositi ve uri ne dr u g test .
6.
Scree ni n g s u pi ne B P ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g ( diast olic) f or 
partici pa nts < 6 0 ye ars; a n d ≥1 5 0/ 9 0 m m/ H g f or partici pa nts ≥6 0 years ol d, f oll o wi n g 
at least 5 mi n utes of s u pi ne rest. If s ys t olic B P is ≥1 4 0 or 1 5 0 m m H g ( base d o n a ge) 
or diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of 
t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s eli gi bilit y . 
7.
Re nal i m pair me nt as defi ne d b y  a n e G F R < 7 5 m L/ mi n/ 1. 7 3 m². Si nce partici pa nts are 
1 8 y ears t o 6 5 years, 2 0 2 1 C K D- EPI  e G F R (c o m bi ne d Screat a n d Sc ys) is t he 
rec o m me n de d f or m ula (see Secti o n 1 0. 7. 2 ) t o deter mi ne eli gi bilit y a n d t o pr o vi de a 
baseli ne t o q ua ntif y  a ny s u bse q ue nt ki d ne y  safet y e ve nts.
8.
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 safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms, 
c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate- a ge m y o car dial i nfarcti o n, S T -T 
i nter val c ha n ges s u g gesti ve of my o car dial isc he mia, sec o n d- or t hir d - de gree A V 
bl oc k, or seri o us bra d yarr h yt h mias or tac h ya rr hyt h mias). If Q Tc F e xcee ds 4 5 0 ms, or 
Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 
3 Q Tc F or Q R S val ues use d t o deter mi ne t he parti ci pa nt’s eli gi bilit y. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 3
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.
9.
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 h e st u d y s pecific- la b orat or y a n d c o nfir me d b y a si n gle 
re peat test, if dee me d necessar y: 

A L T, A S T, t otal b ilir u bi n ≥1. 0 5 × U L N ; partici pa nts wit h a hist or y  of Gil bert’s 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤U L N.
Ot her E xcl usi o n Criteri a :
1 0. 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 1. Use of t o bacc o or nic oti ne- c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nt of 5 
ci garettes/ da y or 2 c he ws of t o bacc o/ da y.
1 2. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers.
5. 3. Lifest yle C o nsi der ati o ns
T he f oll o wi n g g ui deli nes are pr o vi de d:
5. 3. 1. C o ntr ace pti o n 
T he i n vesti gat or or t heir desi g nee, i n c o ns ultati o n wit h t he partici pa nt, will c o nfi r m t hat t he 
partici pa nt is utilizi n g a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual partici pa nt 
a n d t heir part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see A p pe n di x 4 ,
Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. T he i n vesti gat or or desi g nee will a d vi se t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  i nter ve nti o n, if 
a p plica ble.
At ti me p oi nts i n dicate d i n S o A , t he i n vesti gat or or desi g nee will i nf or m t he partici pa nt of 
t he nee d t o use hi g hly effecti ve c o ntrace pti o n c o nsiste ntl y  a n d c orrectl y a n d d oc u me nt t he 
c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart. Partici pa nts nee d t o 
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. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 4
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 wn 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 a p pr o xi matel y 1 0 h o urs pri or t o t he 
c ollecti o n of t he pre d ose P K sa m ple.

N o ncaffei nate d dri n ks (e xce pt gra pefr uit or gra pefr uit -relate d citr us fr uit j uices-see 
bel o w) ma y  be c o ns u me d wit h meals a n d t he e ve ni n g s nac k.

L u nc h will be pr o vi de d a p pr o xi matel y  4 h o urs after d osi n g.

Di n ner will be pr o vi de d a p pr o xi matel y  9 t o 1 0 h o urs after d osi n g.

A n e ve ni n g s nac k ma y  be per mitte d.

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi 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 p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat, a n d 1 5 % pr otei n , wit h t he e xce pti o n of 
d osi n g da y s i n w hic h a hi g h-fat/ hi g h-cal orie meal will be gi ve n pri or t o st u d y  
i nter ve nti o n. T he 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.

O n n o n -d osi n g d ays w hile i n patie nt, as a p pr o priate, sta n dar d m or ni n g meal, l u nc h, 
a n d e ve ni n g meal (al o n g wit h a n e ve ni n g s nac k) are t o be pr o vi de d at a si milar cl oc k 
ti me t o t he cl oc k ti me w he n t hese meals are offere d o n t he d osi n g da y.

D osi n g u n der faste d c o n diti o ns:

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nts will recei ve st u d y
i nter ve nti o n.

Water is per mitte d u ntil 1 h o ur pri or t o st u d y  i nter ve nti o n a d mi nistrati o n. 
Water ma y
be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur after d osi n g.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 5

D osi n g if f o o d effects are i n vesti gate d:

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nts s h o ul d start 
brea kfast a p pr o xi matel y  3 0 mi n utes pri or t o a d mi nistrati o n of st u d y 
i nter ve nti o n.

T he hi g h -fat, hi g h-cal oric brea kfast will be c o ns u me d o ver a p pr o xi mate l y a 
2 0 -mi n ute peri o d wit h st u d y  i nter ve nti o n a d mi nistere d a p pr o xi matel y 
1 0 mi n utes after c o m pleti o n of t he meal at 0 H.

T here are n o water restricti o ns pri or t o d osi n g f or partici pa nts d ose d u n der fe d
c o n diti o ns. Water ma y be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur after
d osi n g.

T he brea kfast will be a hi g h -fat (a p pr o xi matel y 5 0 % of t otal cal oric c o nte nt of 
t he meal), hi g h -cal orie (a p pr o xi matel y 8 0 0 t o 1 0 0 0 cal ories) meal. T he meal 
will c o nsist of a p pr o xi matel y 1 5 0 pr otei n cal ories, 2 5 0 car b o hy drate c al ories, 
a n d 5 0 0 -6 0 0 fat cal ories. A n e xa m ple test meal w o ul d be: 2 e g gs frie d i n 
b utter, 2 stri ps of bac o n ( or 5 0 g of meat or sa usa ge), 2 slices of t oast wit h 
b utter, 4 o u nces (a p pr o xi matel y  1 1 2 gra ms) of has h br o w n p otat oes, a n d 8 
fl ui d o u nces ( 2 4 0 m L) of w h ole mil k. Partici pa nts will be e nc o ura ge d t o 
c ons u me t he e ntire meal.
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 C R U a n d c o nti n ue a bstai ni n g fr o m alc o h ol u ntil c ollecti o n 
of t he fi nal P K sa m ple of eac h st u d y peri o d. Partici pa nt s may u n der g o a n alc o h ol 
breat h test or bl o o d alc o h ol test at t he discreti o n of t he i n vesti gat or.

Partici pa nt s will a bstai n fr o m t he use of t o bacc o- or nic oti ne -c o ntai ni n g pr o d ucts f or 
2 4 h o urs pri or t o d osi n g a n d d uri n g c o nfi ne me nt i n t he C R U. 
5. 3. 4. Acti vit y

Part ici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea vy 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 y s, partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P, p ulse rate , a n d 
E C G meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 
4 h o urs after d osi n g;
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 6

Partici pa nt s will be c o nfi ne d t o t he pr oce d ure r o o m f or t he first 4 h o urs after d osi n g 
o n Da y 1 d uri n g c o nti n u o us car diac m o nit ori n g, e xce pt t o use t he bat hr o o m. After 
t his, if t he e q ui p me nt set u p all o ws, partici pa nt s ma y be a m b ulat or y d uri n g t he E C G 
m o nit ori n g peri o d, b ut s h o ul d n ot e n ga ge i n stre n u o us acti vities. If e q ui p me nt d oes 
n ot all o w a m b ulati o n, a p pr o priate acc o m m o dati o ns will be ma de b y  t he i n vesti gat or 
site t o facilitate c o nti n u o us m o nit ori n g (e g, be dsi de uri nals s h o ul d be pr o vi de d t o 
acc o m m o date partici pa nt s’ e xcret or y nee ds).
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e nr olle d i n t he st u d y. Scree n fail ure data are c ollecte d a n d re mai n as 
s o urce a n d are n ot re p orte d o n t he C R F .
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y be 
rescree ne d. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal a n d n o ni n vesti gati o nal me dici nal 
pr o d ucts/a u xiliar y  me dici nal pr o d ucts, me dical de vices, a n d ot her i nter ve nti o ns (e g, s ur gical 
a n d be ha vi oral) i nte n de d t o be a d mi nistere d t o t he st u d y  partici pa nts d uri n g t he st u d y 
c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o:

P F - 0 7 2 9 3 8 9 3

Place b o f or P F -0 7 2 9 3 8 9 3
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 7
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 2 9 3 8 9 3
Place b o
T y pe
Dr u g
Dr u g
Use
E x peri me ntal
Place b o
I M P or NI M P/ A x M P
I M P
I M P
D ose F or m ul ati o n
B ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns
B ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns
U nit D ose Stre n gt h(s)
Pl a n ne d oral s us pe nsi o n d oses 
ra n gi n g fr o m 1 0 -1 5 0 0 m g
0 m g
D os a ge Le vel(s)
Si n gle asce n di n g d oses 1 0 -1 5 0 0 m g 
(see Secti o n 1. 2 a n d Secti o n 4. 3. 4 )
0 m g
R o ute of A d mi nistr ati o n
Oral
Oral
S o urci n g
Pr o vi de d ce ntrall y b y  t he s p o ns or
Pr o vi de d ce ntrall y b y  t he s p o ns or
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d 
as b ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns . 
Eac h i n di vid ual b ottle 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 as
b ul k p o w der f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns . 
Eac h i n di vi d ual b ottle will be la bele d 
as re q uire d per c o u ntr y re q uire me nt.
S R S D
I B
I B
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 8
St u d y Ar m(s)
A r m  Title
C o h ort 1
C o h ort 2
C o h ort 3 ( O pti o nal)
A r m  Descri pti o n
Partici pa nts will recei ve 
u p t o 4 d oses of 
P F -0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g 
place b o d oses . D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses t o 
be deter mi ne d
Partici pa nts will recei ve 
u p t o 4 d oses of 
P F -0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g 
place b o d oses . D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses t o 
be deter mi ne d
Partici pa nts will recei ve 
u p t o 4 d oses of 
P F -0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of matc hi n g 
place b o d oses . D oses 
will be a d mi nistere d as 
oral s us pe nsi o ns as 
escalati n g si n gle d oses t o 
be deter mi ne d
P F - 0 7 2 9 3 8 9 3 a n d place b o will be pr o vi de d b y  Pfizer as b ul k p o w ders f or e xte m p ora ne o us 
pre parati o n of oral s us pe nsi o ns at t he C R U.

S D D P F -0 7 2 9 3 8 9 3 or place b o oral s us pe nsi o n will be e xte m p ora ne o usl y pre pare d f or 
si n gle d ose ra ng i n g fr o m 1 0 m g t o 1 5 0 0 m g.

Cr y stalli ne P F-0 7 2 9 3 8 9 3 or place b o oral s us pe nsi o n will be e xte m p ora ne o usl y  
pre pare d f or si n gle d ose ra n g i n g fro m 1 0 m g t o 5 0 0 m g.
P F - 0 7 2 9 3 8 9 3 a n d place b o will be prese nte d t o t he partici pa nt s i n i n di vi d ual d osi n g 
c o ntai ners.
6. 1. 1. A d mi nistr ati o n
F or faste d peri o d(s):

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nt s will recei ve st u d y 
i nter ve nti o n at a p pr o xi matel y 0 8: 0 0 h o urs ( pl us or mi n us 2 h o urs) wi t h o ut brea kfast 
o n Da y  1. 
F or fe d peri o d(s):

F oll o wi n g a n o ver ni g ht fast of at least 1 0 h o urs, partici pa nts will recei ve brea kfast 
a p pr o xi matel y 3 0 mi n utes pri or t o d osi n g o n Da y 1 w hic h is t o be c o mplete d wit hi n 
a p pr o xi matel y 2 0 mi n utes as o utli ne d i n Secti o n 5. 3. 2 . T he partici pa nts will t he n 
recei ve st u d y i nter ve nti o n a p pr o xi matel y 1 0 mi n utes after c o m pleti o n of t he meal at 
a p pr o xi matel y 0 8: 0 0 h o urs ( pl us or mi n us 2 h o urs).
F or all peri o ds, i n vesti gat or site pers o n nel will a d mi nister a si n gle oral d ose of st u d y 
i nter ve nti o n o n Da y 1 of eac h peri o d wit h a m bie nt te m perat ure water t o a t otal v ol u me of 
a p pr o xi matel y 2 4 0 m L. A d mi nister st u d y i nter ve nti o n acc or di n g t o t he E D R.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 3 9
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 by 
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 nte r ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y, pre pare, a n d/or a d mi nister st u d y  i nter ve nti o n.
3.
All st u d y  i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d
m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d 
st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. At 
a mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures si nce pre vi o usly d oc u me nte d u p o n 
ret ur n t o b usi ness.
4.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h acti o ns ta ke n. T he site s h o ul d acti vely 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o o n as p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y  i nter ve nti o n m ust be 
q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  
i nter ve nti o n. S pecific details re gar di n g t he e xc ursi o n defi niti o n a n d i nf or mati o n t o
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he C R U 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 by t he st ora ge 
c o n diti o ns state d o n t he la bel. See t he E D R f or st ora ge c o n diti o ns of t he st u d y  
i nter ve nti o n o nce pre pare d.
6.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners.
7.
T he i n vesti gat or, i nstit uti o n, hea d of t he me dical i nstit uti o n ( w here a p plica ble), or 
a ut h orize d site staff is res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y, 
rec o nciliati o n, a n d rec or d mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal 
dis p ositi o n rec or ds) , s uc h as t he IP A L  or s p o ns or-a p pr o ve d e q ui vale nt . All st u d y  
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.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 0
8.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  
i nter ve nti o ns are pr o vi de d i n t he C R U’s pr oce d ures . Al l 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 re g ulati o ns, i nstit uti o nal p olic y , an 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 o r 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, 
partici pa nt , i n acc or da nce wit h t his pr ot oc ol. Local healt h a ut h orit y re g ulati o ns or 
i n vesti gat or site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
P F - 0 7 2 93 8 9 3 a n d place b o oral d osi n g s us pe nsi o ns will be pre pare d i n t he C R U b y  
2 o perat ors, 1 of w h o m is a p har macist. Details of d ose pre parati o n will be gi ve n i n a 
se parate E D R. Pre pare d d oses will be pr o vi de d i n u nit d ose c o ntai ners a n d la bele d i n 
acc or da nce wit h Pfizer re g ulati o ns a n d t he i n vesti gat or site’s la beli n g re q uire me nts.
P F - 0 7 2 9 3 8 9 3 a n d place b o will be pre pare d b y q ualifie d u n bli n de d site pers o n nel acc or di n g 
t o t he E D R . Bli n de d st u d y i nter ve nti o n will be a d mi nistere d i n a bli n d e d fas hi o n t o t he 
partici pa nt . 
6. 3. Assi g n me nt t o St u d y I nter ve nti o n
T he i n vesti gat or will assi g n partici pa nt n u m bers t o t he partici pa nt s as t he y are scree ne d f or 
t he st u d y. Pfizer will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or da nce 
wit h t he ra n d o mizati o n n u m bers, t he partici pa nt will recei ve t he st u d y treat me nt re gi me n 
assi g ne d t o t he c orres p o n di n g ra n d o mizati o n n u m ber.
6. 4. Bli n di n g
T his is a site d o u ble -bli n d (s p o ns or u n bli n de d) st u d y. 
6. 4. 1. Bli n di n g of P a rtici p a nts
Partici pa nts will be bli n de d t o t heir assi g ne d st u d y i nter ve nti o n.
6. 4. 2. Bli n di n g of Site Pers o n nel
I n vesti gat ors a n d ot her site staff will be bli n de d t o partici pa nts’ assi g ne d st u d y i nter ve nti o n. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 3
se nti nel partici pa nts will be re vie we d pri or t o d osi n g t he re mai ni n g partici pa nts of t hat 
peri o d.
6. 6. 1. D ose Esc al ati o n a n d St o p pi n g R ules
D ose escalati o n st o p pi n g r ules will be use d t o deter mi ne w het her t he ma xi mal t olerate d d ose 
has bee n attai ne d. D ose escalati o n ma y  be st o p pe d if it is deter mi ne d t hat t he li mits of safet y 
a n d/ or t olera bilit y ha ve bee n reac he d. T his decisi o n will be ma de after a disc ussi o n ta kes 
place bet wee n t he s p o ns or st u d y  tea m a n d t he i n vesti gat or. T he s p o ns or st u d y tea m ma y n ot 
o verr ule t he i n vesti gat or’s decisi o n t o st o p d ose escalati o n. If d ose escalati o n is st o p pe d 
beca use of a n y of t hese criteria , a d diti o nal c o h orts ma y recei ve t he sa me or l o wer d oses of 
t he st u d y i nter ve nti o n.
T he d ose escalati o n will be ter mi nate d base d o n t he f oll o wi n g criteria:

If 5 0 % or m ore of t he partici pa nt s recei vi n g acti ve dr u g at a gi ve n d ose le vel ( b ut n ot 
partici pa nt s recei vi n g place b o) de vel o p si milar cli nicall y si g nifica nt la b orat or y, E C G, 
or vital si g n a b n or malities, i n t he sa me or ga n class, i n dicati n g d ose -li miti n g 
i nt olera nce.

Se vere n o nseri o us A Es, c o nsi dere d as, at least, p ossi bl y relate d t o st u d y i nter ve nti o n
ad mi nistrati o n, i n 2 partici pa nts at a gi ve n d ose le vel ( b ut n ot partici pa nts recei vi n g 
place b o), i n de pe n de nt of wit hi n or n ot wit hi n t he sa me s yste m or ga n class, i n dicati n g 
d ose -li miti n g i nt olera nce.

D osi n g will be pa use d f or a n y S A E t hat occ urs i n a parti ci pa nt recei vi n g acti ve 
treat me nt u ntil ca usalit y is f ull y assesse d b y t he PI a n d s p o ns or. D osi n g ma y res u me 
if t he S A E is deter mi ne d t o be n ot dr u g-relate d by t he PI a n d s p o ns or. If t he S A E is 
deter mi ne d t o be eit her dr u g-relate d or u n k n o w n, eit her d osi n g will cease or t he S A E 
will be e val uate d b y t he s p o ns or’s pr ot oc ol re vie w c o m mittee ( or si milar re vie w 
gr o u p), w hic h is i n de pe n de nt of t he st u d y  tea m a n d i n vesti gat ors. If t he pr ot oc ol 
re vie w c o m mittee deter mi nes t hat d osi n g ma y res u me, a pla n t hat miti gates ris ks t o 
partici pa nt s wit h t he res u m pti o n of d osi n g will be i m ple me nte d. S uc h a pla n c o ul d 
i ncl u de a re visi o n of i ncl usi o n/e xcl usi o n criteria, re peati n g or re d uci n g t he d ose, or 
a d di n g a p pr o priate safet y m o nit ori n g.

It is deter mi ne d t hat t he li mit of safet y a n d/ or t olera bilit y has bee n reac he d. T his 
decisi o n will be ma de f oll o wi n g disc ussi o ns bet wee n t he st u d y  tea m a n d t he 
i n vesti gat or.

Ot her fi n di n gs t hat, at t he discreti o n of t he st u d y t ea m a n d i n vesti gat or, i n dicate t hat 
d ose escalati o n s h o ul d be halt e d.

If, at a ny d ose le vel, t he a vera ge e x p os ure reac hes or e xcee ds t he P K st o p pi n g li mits, 
t otal C ma x of  
 n g/ m L or t otal A U C 2 4 of  
 n g• h/ m L . I n a d diti o n, i n di vi d ual 
P K data, i ncl u di n g t he ma xi m u m e x p os ure o bser ve d i n i n di vi d ual partici pa nts wit hi n 
a c o h ort will be c o nsi dere d al o n gsi de t he mea n e x p os ures f or t he c o h ort. T he d ose 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 4
escalati o n will be st o p pe d if i n di vi d ual ma xi m u m e x p os ure i n ≥2 partici pa nts reac hes 
or e xcee ds t he P K st o p pi n g li mits, t otal C ma x of  
 n g/ m L or t otal A U C 2 4 of 
 n g• h/ m L.

If, base d o n t he o bser ve d data, t he gr o u p mea n Cma x or A U C ( base d o n t otal plas ma 
c o nce ntrati o n) of t he ne xt pla n ne d d ose is pr ojecte d t o e xcee d t he escalati o n li mits, 
t hat d ose will n ot be e x pl ore d. M o difie d d oses ma y be e x pl ore d if t he y are n ot 
e x pecte d t o e xcee d P K st o p pi n g criteria.
Pr o gressi o n t o t he ne xt d ose will occ ur if t he last d ose was well t olerate d a n d after 
satisfact or y re vie w of t he a vaila ble safety a n d P K data.
6. 7. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y  partici pati o n.
6. 8. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of P F - 0 7 2 9 3 8 9 3 greater t ha n 2 0 0 0 m g wit hi n a 2 4- h o ur ti me peri o d 
will be c o nsi dere d a n o ver d ose.
T here is n o s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or or treati n g p hys icia n s h o ul d:
1.
C o ntact t he st u d y me dical m o nit or wit hi n 2 4 h o urs.
2.
Cl osel y  m o nit or t he partici pa nt f or a ny A E s/ S A Es a n d la b orat or y a b n or malities as 
me dicall y  a p pr o priate a n d f oll o w u p u ntil res ol uti o n, sta bilizati o n, t he e ve nt is 
ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w -u p (as defi ne d i n Secti o n 7. 3 ).
3.
D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n 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 3 da ys fr o m t he date of t he last d ose of 
st u d y i nter ve nti o n if re q ueste d b y t he st u d y me dical m o nit or ( deter mi ne d o n a case b y
case basis).
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he st u d y me dical m o nit or as nee de d base d o n t he cli nical e val uati o n of t he 
partici pa nt.
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of pre scri pti o n or n o n prescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n t hr o u g h t he last P K c ollecti o n, wit h t he 
 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 5
 w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o t he first 
d ose of st u d y  i nter ve nti o n.
A n o n -e x ha usti ve list of 
 is i n 
A p pe n di x 9 . Beca use t his is n ot a n all-i ncl usi ve list, site staff s h o ul d c o ns ult wit h t he s p o ns or 
or desi g nee wit h a n y q uesti o ns re gar di n g p ote ntial D DI.
Li mite d use of n o n prescri pti o n me dicati o ns t hat are n ot belie ve d t o affect partici pa nt safet y 
or t he o verall res ults of t he st u d y  ma y be per mitte d o n a case b y case basis f oll o wi n g 
a p pr o val b y t he s p o ns or . Aceta mi n o p he n/ paraceta m ol ma y  be use d at d oses of ≤1 g/ da y .
Fe males ta ki n g h or m o ne re plac e me nt t hera p y m a y be eli gi ble t o partici pate i n t his st u d y if 
t he y are willi n g t o disc o nti n ue t hera p y at least 2 8 da y s pri or t o t he first d ose of st u d y 
treat me nt a n d re mai n off h or m o nal t hera py f or t he d urati o n of t he st u d y.
All c o nc o mita nt treat me nts ta ke n d uri n g t he st u d y  m ust be rec or de d wit h i n dicati o n, dail y 
d ose, a n d start a n d st o p dates of a d mi nistrati o n. All partici pa nts will be q uesti o ne d a b o ut 
c o nc o mita nt treat me nt at eac h cli nic visit.
Treat me nts ta ke n wit hi n 2 8 da y s bef ore t he first d ose of st u dy 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 2 9 3 8 9 3; 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 Es , or s o me 
ot her (a d mi nistrati ve) reas o ns .
D isc o nti n uati o n of st u d y i nter ve nti o n d oes n ot re prese nt wit h dra wal fr o m t he st u d y. If st u d y 
i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt s h o ul d re mai n i n t he st u d y t o be 
e val uate d f or o n g oi n g A Es . See t he S o A f or data t o be c ollecte d at t he ti me of 
disc o nti n uati o n of st u d y  i nter ve nti o n a n d f oll o w-u p f or a n y  f urt her e val uati o ns t hat nee d t o 
be c o m plete d.
I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be d oc u me nte d o n t he 
a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is disc o nti n ui n g f urt her 
recei pt of st u dy i nter ve nti o n or als o fr o m st u d y  pr oce d ures, f urt her st u d y f oll o w-u p, a n d/ or 
f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 6
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 C L) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter- me diate d effect 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 ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y c o ns ultati o n.
F oll o w -u p Assess me nts
T he partici pa nt s h o ul d ret ur n t o t he site f or e val uati o n as s o o n as p ossi ble, prefera bl y wit hi n 
4 8 h o urs of a ware ness of t he a b n or mal res ults. 
E val uati o n s h o ul d i ncl u de p h y sical e xa mi nati o n, la b orat or y tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs an d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates of e G F R, e Cr Cl a n d Screat -base d e G F R a n d c o m bi ne d 
Screat -S c y s-base d e G F R s h o ul d als o be deri ve d usi n g t he a p pr o priate e q uati o n descri be d i n 
A p pe n di x 7 .
Assess me nts of uri ne al b u mi n -t o-creati ni ne rati o or uri ne v ol u me ma y als o be perf or me d as 
a p pr o priate.
Differe nti ati n g Ac ute Ki d ne y I nj ur y fr o m DI CI
A c o nfir me d Screat i ncrease is defi ne d as:
(i) ≥0. 3 m g/ d L ( ≥2 6. 5 µ m ol/ L) wit hi n 4 8 h o urs O R 
(ii) c o nfir me d Screat i ncrease ≥1. 5 ti mes baseli ne ( k n o w n or s us pecte d t o ha ve occ urre d 
wit hi n t he pri or 7 da y s). 
Base d o n t he assess me nts perf or me d, s us pecte d A KI (i ncl u di n g DI KI) ma y be differe ntiate d 
fr o m DI CI as f oll o ws.
A d ult p artici p a nts
A KI (i nc l 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 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 7
A KI (i nc l u di n g DI KI)
A n y o ne of t he bel o w
DI CI
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)
C o nfir me d Screat -base d e G F R 
decrease w ith o ut c o nfir me d c o m bi ne d 
Screat -Sc ys -base d e G F R decrease.
Al b u mi n uria or 
pr otei n uria
C o nfir me d al b u mi n uria i ncrease (see 
A p pe n di x 7 f or Gra des A 1 t o A 3 
q ua ntitati o n)
Uri ne v ol u me
Uri ne v ol u me < 0. 5 m L/ k g/ h f or 6 
c o nsec uti ve h o urs
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is ne w-o nset or w orse ni n g al b u mi n uria or pr otei n uria are 
detecte d.
All c o nfir me d cases of cli nicall y  rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d 
p ote ntial cases of DI KI if n o ot her reas o n f or t he ki d ne y  f u ncti o n a b n or malities has bee n 
f o u n d.
7. 1. 2. E C G C h a n ges 
A partici pa nt w h o meets eit her b ullete d criteria base d o n t he a vera ge of tri plicate E C G 
rea di n gs will be wit h dra w n fr o m t he st u 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.
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 ny 
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
7. 1. 3. C O VI D - 1 9
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n A E or S A E (as 
a p pr o priate) a n d a p pr o priate me dical i nter ve nt i o n pr o vi de d. St u d y  treat me nt s h o ul d c o nti n ue 
u nless t he i n vesti gat or/treati n g p h ys icia n is c o ncer ne d a b o ut t he safety of t he partici pa nt, i n 
w hic h case te m p orar y  or per ma ne nt disc o nti n uati o n ma y be re q uire d.
It is rec o m 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 ve nti o n wit h t he st u d y me dical m o nit or. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 8
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 f r o m t he st u d y i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ure;

L ost t o f oll o w - u p

Deat h ;

St u d y  ter mi nate d b y s p o ns or;

Discreti o n of t he i n vesti gat or or s p o ns or f or safet y or be ha vi oral reas o ns, or t he 
i na bilit y of t he partici pa nt t o c o m pl y wit h t he pr ot oc ol re q uire d sc he d ule of st u d y  
visits or pr oce d ures.
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d . See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y. Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
T he partici pa nt will be per ma ne ntl y disc o nti n ue d fr o m t he st u d y i nter ve nti o n a n d t he st u d y  at 
t hat ti me.
If a partici pa nt wit h dra ws fr o m t he st u d y, t he y m a y  re q uest destructi o n of a n y  re mai ni n g 
sa m ples ta ke n a n d n ot teste d, a n d the i n vesti gat or m ust d oc u me nt a n y  s uc h re q uests i n t he 
site st u d y rec or ds a n d n otif y t he s p o ns or acc or di n gl y.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt (see Secti o n 7. 2. 1 f or 
discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns will be perf or me d a n d n o a d diti o nal 
data will be c ollecte d. T he s p o ns or ma y  retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore 
s uc h wit h dra wal of c o nse nt.
7. 2. 1. Wit h dr a w al of C o nse nt 
Partici pa nt s w h o re q uest t o disc o nti n ue recei pt of st u d y i nter ve nti o n will re mai n i n t he st u d y  
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol s pecifie d- f oll o w- u p pr oce d ures. T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecifically wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h t he m or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his i nf or mati o n. 
Partici pa nt s s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt 
fr o m f ut ure f oll o w- u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y  fr o m 
f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures a n d/ or p osttreat me nt st u d y 
f oll o w- u p-, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat vital stat us ( w het her 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 4 9
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 
u se d t o deter mi ne vital stat us o nl y as a p pr o priatel y directe d i n acc or da nce wit h l ocal la w.
7. 3. L ost t o F oll o w -U p 
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if t he partici pa nt re peate dl y fails t o ret ur n 
f or sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa n t a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble. Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d;

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, t he partici pa nt will be c o nsi dere d 
t o ha ve wit h dra w n fr o m t he st u d y. 
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
8. 1. A d mi nistr ati ve P r oce d ures
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y s pecific- pr oce d ures. 
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o n fir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Partici pa nts wi ll be scree ne d wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he st u d y i nter ve nti o n 
t o c o nfir m t hat t he y meet t he st u d y p o p ulati o n criteria f or t he st u d y. If t he ti me bet wee n 
scree ni n g a n d d osi n g e xcee ds 2 8 d a y s as a res ult of u ne x pecte d dela ys (e g, dela ye d dru 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.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 0
A partici pa nt w h o q ualifie d f or t his pr ot oc ol b ut di d n ot e nr oll fr o m a n earlier c o h ort/ gr o u p 
ma y  be use d i n a s u bse q ue nt c o h ort/ gr o u p wit h o ut rescree ni n g, pr o vi de d la b orat or y  res ults 
o btai ne d pri or t o t he first d ose a d mi nistrati o n meet eli gi bilit y  criteria f or t his st u d y. I n 
a d diti o n, ot her cli nical assess me nts or s peci me n c ollecti o ns, e g, retai ne d researc h sa m ples, 
ma y  n ot nee d t o be re peate d , as a p pr o priate.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol re q uire d- tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma ke it u nfeasi ble t o perf or m t he 
test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
well -bei n g of t he partici pa nt . W he n a pr ot oc ol re q uire d- test ca n n ot be perf or me d, t he 
in 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 n y 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 nner.
Safet y , la b orat or y, or a nal yte res ults t hat ha ve bee n c ollecte d f or t he p ur p oses of t his st u d y  
a n d c o ul d u n bli n d t he st u d y will n ot be re p orte d t o i n vesti gati ve sites or ot her bli n de d 
pers o n nel u ntil t he st u d y  has bee n u n bli n de d.
If a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g n assess me nts 
(p ulse rate a n d B P) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr uctio 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 
4 8 0 m L . T he act ual c ollecti o n ti mes of bl o o d sa m pli n g ma y c han ge. A d diti o nal bl o o d 
sa m ples ma y be ta ke n f or safety assess me nts at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal 
v ol u me ta ke n d uri n g t he st u d y  d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d of 5 6 c o nsec uti ve 
da y s.
T o pre pare f or st u d y partici pati o n, partici pa nt s will be i nstr ucte d o n t he i nf or mati o n i n t he 
Lifest y le C o nsi derati o ns a n d C o nc o mita nt T hera p y secti o ns of t he pr ot oc ol.
8. 2. Effic ac y Assess me nts
Efficac y  para meters are n ot e val uate d i n t his st u d y. 
8. 3. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d safet y
meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess a n y percei ve d safet y 
iss ues.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 2
T he sa me pr o perl y size d a n d cali brate d B P c uff will be use d t o meas ure B P eac h ti me. T he 
use of a n a ut o mate d de vice f or meas uri n g B P a n d p ulse rate is acce pta ble; h o we ver, w he n 
d o ne ma n uall y, p ulse rate will be meas ure d i n t he brac hial/ra dial arter y  f or at least 
3 0 sec o n ds. W he n t he ti mi n g of t hese meas ure me nts c oi nci des wit h a bl o o d c ollecti o n, B P 
a n d p ulse rate s h o ul d be o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n.
A d diti o nal c ollecti o n ti mes, or c ha n ges t o c ollecti o n ti mes, of B P a n d p ulse rate will be 
per mitte d, as necessar y, t o e ns ure a p pr o priate c ollecti o n of safet y  data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri ng t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 3. 2. Res pir at or y R ate 
Res pirat or y  rate will be meas ure d after a p pr o xi matel y 5 mi n utes 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. 3. Te m per at ure 
Te m perat ure will be meas ure d orall y. N o eati n g, dri n ki n g, or s m o ki n g is all o we d f or 
1 5 mi n utes pri or t o t he meas ure me nt.
8. 3. 4. Electr oc ar di o gr a ms
St a n dar d 1 2 -lea d E C Gs will be c ollecte d at ti mes s pecifie d i n t he S o A secti o n of t his 
pr ot oc ol usi n g a n E C G s yste m t hat a ut o maticall y calc ulates t he H R a n d meas ures P R, Q T, 
Q Tc F, a n d Q R S i nter vals. All sc he d ule d E C Gs s h o ul d be perf or me d after t he partici pa nt has 
reste d q uietly f or at least 5 mi n utes i n a s u pi ne p ositi o n. 
Tri plicate 1 2 -lea d E C Gs (as s pecifie d i n t he S o A ) will be o btai ne d a p pr o xi matel y  2 t o 
4 mi n utes a part; t he a vera ge of t he tri plicate E C G meas ure me nts c ollecte d at - 1. 0, -0. 5, a n d 
0 h o urs pre -d ose o n Da y 1 of eac h peri o d will ser ve as eac h partici pa nt ’s baseli ne Q TcF
val ue f or t hat peri o d. 
T o e ns ure safet y of t he partici pa nt s, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o baseli ne meas ure me nts. A d diti o nal E C G m o nit ori n g will occ ur if a) t he mea n 
val ue fr o m t he tri plicate meas ure me nts f or a n y p ost -d ose Q Tc F i nter val is i ncrease d b y 
≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n abs ol ute Q T val ue is ≥5 0 0 ms f or a ny 
sc he d ule d E C G. If eit her of t hese c o n diti o ns occ urs, t he n a si n gle E C G meas ure me nt m ust be 
re peate d at least h o url y u ntil Q TcF 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 ur e me nt.
F or si n gle E C G c ollecti o ns, 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 ms fr o m t he baseli ne a n d is > 4 5 0 ms; or b) a n a bs ol ute Q T val ue 
is ≥5 0 0 ms f or a n y  sc he d ule d E C G. If eit her of t hese c o n diti o ns occ urs, t he n 2 a d diti o nal 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 3
E C Gs will be c ollecte d a p pr o xi matel y  2 - 4 mi n utes a part t o c o nfir m t he ori gi nal 
meas ure me nt. If t he Q Tc F val ues fr o m t hese re peate d E C Gs re mai n a b o ve t he t hres h ol d 
val ue, t he n a si n gle E C G m ust be re peate d at least h o url y  u ntil Q Tc values fr o m 2 s uccessi ve 
E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat meas ure me nt.
If a) a p ost -d ose Q Tc F i nter val re mai ns ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a ny sc he d ule d E C G f or greater t ha n 4 h o urs ( or s o o ner, at 
t he discreti o n of t he i n vesti gat or); or c) Q Tc F val ue get pr o gressi vel y  l o n ger, t he partici pa nt
s h o ul d u n der g o c o nti n u o us E C G m o nit ori n g. A car di ol o gist s h o ul d be c o ns ulte d if Q TcF
val ues d o n ot ret ur n t o less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
I n s o me cases, it ma y be a p 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 ort a nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne-rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o vi der’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 8 .
8. 3. 4. 1. C o nti n u o us C ar di ac M o nit ori n g b y Tele metr y
All a b n or mal r h yt h ms will be rec or de d a n d re vie we d b y  t he st u d y p h ysicia n f or t he prese nce 
of r h yt h ms of p ote ntial cli nical c o ncer n. T he ti me, d urati o n, a n d descri pti o n of t he cli nicall y 
si g nifica nt e ve nt will be rec or de d i n t he C R F. I n a d diti o n, a pri nte d rec or d of t he traci n g(s) of 
t he cli nicall y si g nifica nt r hyt h m(s) will be ma de a n d retai ne d wit h ot her s o urce d oc u me nts.
Tele metr y  s h o ul d be c ollecte d usi n g a ce ntralize d s yste m t hat als o all o ws f or t he st ora ge a n d 
a d va nce d a nal ys is of all rec or de d data i n or der t o preser ve i m p orta nt e ve nts f or f ut ure 
e val uati o ns . H olter m o nit ori n g s h o ul d n ot be use d i n parallel wit h c o nti n u o us tele metr y, 
u nless it is t he o nl y  mea ns of data st ora ge a vaila ble at t he i n vesti gat or site, or verifia ble 
arr h yt h mia q ua ntificati o n is re q uire d. T o esta blis h a baseli ne, tele metr y  s h o ul d be rec or de d 
f or at least 2 h o urs bef ore d osi n g i n Peri o d 1. T his ma y  be d o ne i m me diatel y pri or t o d osi n g 
or at s o me 2 -h o ur c o nti n u o us i nter val i n t he 2 4 h o urs pri or t o d osi n g, as l o n g as t he rec or di n g 
is perf or me d w he n t he partici pa nt is a wa ke. P ost -d ose tele metr y  will c o nti n ue f or 8 h o urs 
after d osi n g. Tele metr y  ma y be st o p pe d wit hi n a reas o na bly s h ort peri o d of ti me pri or t o 
d osi n g, i n or der t o a v oi d i nterfere nce wit h st u d y o perati o ns c o n d ucte d i m me diatel y bef ore 
d osi n g. H o we ver, it is e x pecte d t hat t he tele metr y  lea ds will be i n place a n d t he s yste m 
c o n necte d pri or t o d osi n g.
8. 3. 5. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A .
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 4
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 o cc 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 2 8 da y s after t he last d ose of st u d y i nter ve nti o n s h o ul d be 
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 a n d t he s p o ns or n otifie d.
See A p pe n di x 6 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
DI LI .
See A p pe n di x 7 f or i nstr ucti o ns f or la b orat or y testi n g t o m o nit or ki d ne y f u ncti o n a n d 
re p orti n g la b orat or y test a b n or malities.
Partici pa nt s ma y u n der g o ra n d o m uri ne dr u g testi n g at t he discreti o n of t he i n vesti gat or. 
Dr u g testi n g c o n d ucte d pri or t o d osi n g m ust be ne gati ve f or partici pa nt s t o recei ve st u d y 
i nter ve nti o n. 
8. 3. 6. 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 per C R U pr oce d ures.
8. 4. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A E s ma y arise fr o m sy m pt o ms or ot her c o m plai nts re p orte d t o t he i n 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 healt hcare pr o vi ders (cli nical si g ns, test res ults, etc).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o ass ess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o nti n ue 
t he st u d y (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 Safet y t o o btai n s pecific f oll o w - u p 
i nf or mati o n i n a n e x pe dite d fas hi o n.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 5
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 p a nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A Es or S A E s after t he 
partici pa nt has c o ncl u de d st u d y partici pati o n. H o we ver, if t he i n vesti gat or lear ns of a ny S A E, 
i ncl u di n g a deat h, at a ny ti me after a partici pa nt has c o ncl u de d st u d y part ici pati o n, a n d t he y
c o nsi der t he e ve nt t o be reas o na bl y relate d t o t he st u d y  i nter ve nti o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m / P S S A .
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n 
Secti o n 8. 4. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m / P S S A 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 E s a n d S A Es o n the C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 4. 1 , will be rec or de d 
o n t he A E secti o n of t he C R F.
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y re p orte d 
A E s a n d S A Es re p orte d b y t he partici pa nt.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 6
As part of o n g oi n g safet y re vie ws c o n d ucte d b y t he s p o ns or, a n y n o nseri o us A E t hat is 
deter mi ne d b y t he s p o ns or t o be seri o us will be re p orte d b y  t he s p o ns or as a n S A E. T o assist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
Re p orti n g of A E s a n d S A Es f or partici pa nts w h o fail scree ni n g are s u bject t o t he C R F 
re q uire me nts as descri be d i n Secti o n 5. 4 .
8. 4. 2. Met h o d of Detecti n g A E s a n d S A Es
T he met h o d of rec or di n g, e val uati n g, a n d assessi n g ca usalit y  of AEs a n d S A 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 AE s a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 4. 3. F oll o w - Up of A E s a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi 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 
an 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 ve sti 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 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 7
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 n cl 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 o f 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 ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n c o ntact t he n i nse mi nates his fe male 
part ner pri or t o or ar o u n d t he ti me of c o nce pti o n .
T he i n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial i nf or mati o n s u b mitte d 
s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y). 

If E D P occ urs i n a partici pa nt or 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 Pf izer 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 or via P S S A 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 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 8

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 ort F or m a n d E D P S u p ple me ntal 
F or m or via P S S A . 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 ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr oss vis ual i ns pecti o n ( u nless pre -pr oce d ur e 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 utco mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n s h o ul d be re p orte d 
as a n S A E ;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es. I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or. F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case-b y -case basis (e g, f oll o w- u p o n 
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 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 5 9
e n vir o n me ntal E D B is a fe male fa mily me m ber or healt hcare pr o vi der w h o re p orts 
t hat s he is breastfee di n g after ha vi n g been 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 or via P S S A . 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 or via P S S A 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 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 0
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 / PS S A t o 
Pfizer S afet y Wit hi n 2 4 
H o urs of A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y  A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y  if ass ociate d wit h a n 
S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y partici pa nt .

T he a d mi nistrati o n of e x pire d st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect d osa ge;

T he a d mi nistrati o n of st u d y  i nter ve nti o n t hat has u n der g o ne te m perat ure e xc ursi o n 
fr o m t he s pecifie d st ora ge ra n ge, u nless it is deter mi ne d b y t he s p ons or t hat t he st u d y  
i nter ve nti o n u n der q uesti o n is acce pta ble f or use.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, suc h me dicati o n err ors occ urri n g t o a st u d y  partici pa nt are rec or de d o n t he 
me dicati o n er r 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 / P S S A o nl y w he n ass oci ate d wit h a n S A E.
8. 5. P h ar m ac o ki netics 
8. 5. 1. Pl as m a f or A n al ysis of P F -0 7 2 9 3 8 9 3 C o nce ntr ati o n 
Bl o o d sa m ples of a p pr o xi matel y  3 m L, t o pr o vi de a p pr o xi matel y 1. 2 m L plas ma, will be 
c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of P F - 0 7 2 9 3 8 9 3 i nt o a p pr o priately 
la bele d t u bes c o ntai ni n g K2E D T A as s pecifie d i n t he S o A . I nstr ucti o ns f or t he c ollecti o n 
i ncl u di n g a n y p ote ntial a d diti ve i nf or mati o n, pr ocessi n g, ali q u oti n g, ha n dli n g, st ora ge, a n d 
s hi p me nt of bi ol o gical sa m ples will be pr o vi de d i n t he la b orat or y ma n ual or b y  t he s p o ns or. 
T he act ual date a n d ti me ( 2 4- h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 1
All eff orts will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. 
C ollecti o n of sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are
o btai ne d wit hi n 1 0 % of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n u tes of a 
6 0 - mi n ute sa m ple) will n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of 
t he c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 
1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y  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. T his pr ot oc ol de viati o n wi n d o w 
d oes n ot a p pl y  t o sa m ples t o be c ollecte d m ore t ha n 1 0 h o urs after d ose a d mi nistrati o n at 
o ut patie nt/f oll o w -u p visits wit h visit wi n d o ws.
Sa m ples will be use d t o e val uate t he P K of P F -0 7 2 9 3 8 9 3 . Sa m ples c ollecte d f or a nalys es of 
P F - 0 7 2 9 3 8 9 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 h e 
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 2 9 3 8 9 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.
Dr u g c o nce ntrati o n i nf or mati o n t hat ma y  u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gator sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d in t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt . T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
A 4 m L  bl o o d P G x sa m ple f or D N A is olati o n will be c ollecte d as s pecifie d i n t he S o A . D N A 
sa m ples ma y be a nal yze d f or e val uati o n of ge netic varia nts ass ociate d wit h variati o n i n P K, 
bi o mar ker res p o nse, or t o e x pl ore A Es s h o ul d t hese be o bser ve d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 2
See A p pe n di x 5 f or i nf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b ma n ual a n d ot her 
s u p p orti n g d oc u me ntati o n.
8. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
Retai ne d researc h sa m ples f or ge netics will n ot be c ollecte d i n t his st u d y . 
8. 7. Bi o m ar kers
8. 7. 1. S pecifie d Ge ne E x pressi o n ( R N A) Rese arc h
S pecifie d ge ne e x pressi o n ( R N A) researc h is n ot i ncl u de d i n t his st u d y .
8. 7. 2. S pecifie d Pr otei n Rese arc h 
A 4 m L  bl o o d sa m ple will be c ollecte d i n a re d-t o p ser u m ve n o us bl o o d c ollecti o n t u be ( n o 
ser u m se parat ors) at t he ti me p oi nt s o utli ne d i n t he S o A .
Ser u m sa m ples ma y be use d f or e x pl orat or y a nal ysis of circ ulat or y bi o mar kers of A M P Kγ 3 
acti vati o n an d/ or t o u n der sta n d t he ti me-de pe n de nt pr ofile of circ ulat or y  bi o mar ker c ha n ges 
f oll o wi n g P F-0 7 2 9 3 8 9 3 treat me nt . Res i d ual sa m ples ma y als o be use d t o a nal yze n o n-dr u g 
meta b oli tes i n res p o nse t o st u d y i nter ve nti o n. 
8. 7. 3. S pecifie d Met a b ol o mic Rese arc h 
S pecifie d meta b ol o mic researc h is n ot i ncl u de d i n t his st u d y.
8. 7. 4. Ret ai ne d Rese arc h S a m ples f or Bi o m ar kers
Retai ne d researc h sa m ples f or bi o mar kers will n ot be c ollecte d i n t his st u d y . 
8. 7. 5. Pl as m a f or A n al ysis of Bi o m ar ker(s) of Tr a ns p orter Acti vit y
A 3 m L  bl o o d sa m ple t o pr o vi de a p pr o xi matel y 1. 2 m L of plas ma, will be c ollecte d i nt o 
a p pr o priatel y la bele d a m ber c ol ore d t u bes c o ntai ni n g K2E D T A f or meas ure me nt of plas ma 
bi o mar ker (s), as s pecifie d i n t he S o A .
F ur t her i nstr ucti o ns f or t he c ollecti o n, ha n dli n g, pr ocessi n g, st ora ge, a n d s hi p me nt of 
bi ol o gical sa m ples will be pr o vi de d i n t he la b orat or y  ma n ual or b y t he s p o ns or. T he act ual 
date a n d ti me ( 2 4 -h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
Plas ma s a m ples c ollecte d f or bi o mar ker (s) m a y  als o be use d t o e val uate safet y or efficac y or 
P K 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 y tical met h o d, or f or t he meas ure me nt of P K bi o mar kers or 
f or ot her i nter nal e x pl orat or y p ur p oses.
All eff orts will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. 
C ollecti o n of sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are
o btai ne d wit hi n 1 0 % of t he n o mi nal ti me relati ve t o d o si 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 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 3
t he c ollecti o n is n ote d o n t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 
1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y 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. T his pr ot oc ol de viati o n wi n d o w 
d oes n ot a p pl y  t o sa m ples t o be c ollecte d m ore t ha n 1 0 h o urs after d ose a d mi nistrati o n at 
o ut patie nt/f oll o w -u p visits wit h visit wi n d o ws.
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 ut ilizati 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 he sis
N o f or mal statistical h y p ot hesis testi n g will be perf or me d i n t his st u d y .
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d 
“E nr olle d ” mea ns a partici pa nt ’s a gree me nt t o partici pate i n a 
cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess a n d ra n d o mizati o n t o st u d y i nter ve nti o n.
Safet y anal ys is set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y i nter ve nti o n. Partici pa nts will 
be a nal yz e d acc or di n g t o t he st u d y i nter ve nti o n t he y act ually 
recei ve d.
P K C o nce ntrati o n Set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o recei ve at least 1 d ose of st u d y  i nter ve nti o n a n d i n w h o m 
at least 1 plas ma c o n ce ntrati o n val ue is re p orte d.
P K Para meter Set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o recei ve at least 1 d ose of st u d y  i nter ve nti o n a n d ha ve at 
least 1 of t he P K para meters of i nterest calc ulate d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 4
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.
Briefl y, f or t he a nal ys is of t he pri mar y  e n d p oi nt of safety, t he s p o ns or data sta n dar d r ules f or 
i m p utati o n will be a p plie d t o ha n dle missi n g safet y data. I n all P K data prese ntati o ns (e xce pt 
listi n gs), c o nce ntrati o ns bel o w t he li mit of q ua ntificati o n will be set t o zer o. F or P K s u m mar y  
ta bles a n d pl ots of mea n/ me dia n pr ofiles, statistics will be calc ulate d ha vi n g set 
c o nce ntrati o ns t o missi n g if o ne of t he f oll o wi n g cases is tr ue: 
1.
A c o nce ntrati o n has bee n c ollecte d as N D (ie, n ot d o ne) or N S (ie , n o sa m ple );
2.
A de viati o n i n sa m pli n g ti me is of s ufficie nt c o ncer n or a c o nce ntrati o n has bee n 
fla g ge d a n o mal o us b y t he p har mac o ki neticist/statisticia n.
If a P K para meter ca n n ot be deri ve d fr o m a partici pa nt’s c o nce ntrati o n data, t he para meter 
will be c o de d as N C (ie n ot calc ulate d) a n d set t o missi n g f or s u m mar y ta bles a n d a nalys es.
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. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
A Es, E C Gs, B P, p ulse rate, c o nti n u o us car diac m o nit ori n g, a n d safet y la b orat or y  data will be 
re vie we d a n d s u m marize d o n a n o n g oi n g basis d uri n g t he st u dy t o e val uate t he safet y of 
partici pa nts. A n y cli nical la b orat or y, E C G, B P, p ulse rate , res pirat or y rate, a n d/ or 
te m perat ure a b n or malities 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, ne ur ol o gical e xa mi nati o n, a n d c o nti n u o us car diac 
m o nit ori n g dat a, 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, a n d c o nti n u o us car diac m o nit ori n g 
data, c o n d ucte d d uri n g t he acti ve c ollecti o n peri o d will be ca pt ure d as A Es, if t h ose fi n di n gs 
meet t he defi niti o n of a n A E. 
Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as la b orat or y  
data, E C Gs, a n d vital si g ns, will be c o nsi dere d s o urce data, a n d will n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.
9. 3. 1. 1. Electr oc ar d i o gr a m A n al yses
C ha n ges fr o m baseli ne f or t he E C G para meters H R, Q T i nter val, Q Tc F i nter val, P R i nter val, 
a n d Q R S c o m ple x will be s u m marize d b y  treat me nt a n d ti me. T he fre q ue nc y of u nc orrecte d 
Q T val ues a b o ve 5 0 0 ms will be ta b ulate d.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 6
T a ble 4 .
Pl as m a P F - 0 7 2 9 3 8 9 3 P K P ar a meters
P a r a m eter
Defi niti o n
M e t h o d of Deter mi n ati o n
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 u rre nce
t½ *
T er m i nal eli mi nati o n half-life
L o g e( 2)/ kel, w here kel is t he ter mi nal p hase rate 
c o nsta nt calc ulate d b y a li near re gressi o n of t he 
l o g-li near c o nce ntrati o n-ti me c ur ve. O nl y t h ose 
data p oi nts j u d ge d t o descri be t he ter mi nal l o g-
li near decli ne will be use d i n t he re gressi o n.
C L/ F *
A p pare nt cleara nce
D ose/ A U C i nf
Vz/ F *
A p pare nt v ol u me of distri b uti o n
D ose/( A U C i nfk el)
A U C last( d n)
D ose -n or m alize d A U C last
A U C last/ D ose
A U C i nf( d n) *
D ose -n or m alize d A U C i nf
A U C i nf/ D ose
C ma x ( d n)
D ose -n or m alize d C ma x
C ma x / D ose
* As data per mits
9. 3. 2. 2. St atistic al Met h o ds f or P K D at a 
Plas ma c o nce ntrati o ns of P F- 0 7 2 9 3 8 9 3 will be liste d a n d s u m marize d descri pti vel y  b y d ose 
(f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) a n d n o mi nal P K sa m pli n g ti me. I n di vi d ual 
partici pa nt a n d me dia n pr ofiles of t he plas ma c o nce ntrati o n -ti me data will be pl otte d b y d ose 
(f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) usi n g act ual (f or i n di vi d ual) a n d n o mi nal 
(f or me dia n) ti mes res pecti vel y. Me dia n pr ofiles will be prese nte d o n b ot h li near a n d l o g 
scales.
T he plas ma P K para meters will be s u m marize d descri pti vel y  b y d ose (f or m ulati o n a n d 
fasti n g c o n diti o n, if a p pr o priate) as a p plica ble. D ose-n or malize d A U C i nf, A UC last, a n d C ma x
will be pl otte d a gai nst d ose (f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) usi n g a 
l o garit h mic scale, a n d will i ncl u de i n di vi d ual partici pa nt val ues a n d t he ge o metric mea ns f or 
eac h d ose. T hese pl ots will be use d t o u n dersta n d t he relati o ns hi p be t wee n t he P K para meters 
a n d d ose ( f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate).
If t he f or m ulati o n a n d/or f o o d effect is assesse d, a mi xe d effects A N O V A will be perf or me d 
se paratel y o n t he nat ural l o g tra nsf or me d A U Ci nf, A UC last, a n d C ma x ( d ose-n or ma lize d pri or 
t o a nal ysis, if a p pr o priate) wit h f or m ulati o n a n d/ or fasti n g c o n diti o n i ncl u de d as a fi xe d 
effect a n d partici pa nt as a ra n d o m effect. F urt her details of t his a nal y sis will be pr o vi de d i n 
t he S A P, w here m odificati o ns t o t he m o del ma y  be o utli ne d de pe n di n g o n d osi n g sc he ma 
i m ple me nte d.
A d diti o nal P K a nal y ses ma y be perf or me d if dee me d a p pr o priate a n d ma y n ot be i ncl u de d i n 
t he C S R.
9. 3. 3. Terti ar y/ E x pl or at or y E n d p oi nt(s) A n al ysis
T he a nal ys is of tertiar y/e x pl orat or y e n d p oi nts will be detaile d i n t he S A P.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 7
9. 3. 4. Ot her A n al yses 
P har mac o ge n o mic or bi o mar ker data fr o m s pecifie d ge netics a n d s pecifie d pr otei n bi o mar ker 
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 nal ys es are n ot pla n ne d t o be i ncl u de d i n t he C S R.
9. 4. I nteri m A n al yses
N o f or mal i nteri m a nal ys is will be c o n d ucte d f or t his st u d y. 
9. 5. S a m ple Size Deter mi n ati o n
A sa m ple size of a p pr o xi matel y 2 4 healt h y a d ult partici pa nts ( u p t o 3 c o h orts of 
a p pr o xi matel y 8 partici pa nts eac h) has bee n c h ose n base d o n t he nee d t o mi ni mize first 
e x p os ure t o h u ma ns of a ne w c he mical e ntit y  a n d t he re q uire me nt t o pr o vi de a de q uate safety, 
t olera bilit y, a n d P K assess me nt at eac h d ose le vel. At eac h d ose le vel, 6 partici pa nts are 
pla n ne d t o recei ve P F - 0 7 2 9 3 8 9 3 a n d 2 partici pa nts are pla n ne d t o recei ve place b o wit h all 
partici pa nts at t he e n d of t he st u d y  ha vi n g recei ve d u p t o 4 d oses of P F-0 7 2 9 3 8 9 3 a n d u p t o 
2 d oses of place b o.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 8
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 bs ta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y 
a p pr o val pri or t o i nitiati o n e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n uall y or 
m ore fre q ue ntl y  i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/ E C;

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures ;

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H G C P g ui deli nes, t he I R B/ E C, E ur o pea n re g ulati o n 
5 3 6/ 2 0 1 4 f or cli nical st u dies, E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h, a n d all ot her a p plica ble l ocal re g ulati o ns .
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area o f t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 6 9
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diately of a n y ur ge nt safet y meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nt s a gai nst a ny i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. Fi n a nci al Discl os ure
N ot a p plica ble. 
1 0. 1. 3. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or t he i n vesti gat or's re prese ntati ve will e x plai n t he nat ure of t he st u d y , 
i ncl u di n g t he ris ks a n d be nefits, t o t he partici pa nt a n d a ns wer all q uesti o ns re gar di n g t he 
st u d y. T he partici pa nt s h o ul d be gi ve n s ufficie nt ti me a n d o p p ort u nit y  t o as k q uesti o ns a n d t o 
deci de w het her or n ot t o partici pate i n t he trial.
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts will be 
re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, 
l ocal re g ulati o ns, I C H g ui deli nes, pri vac y  a n d data pr otecti o n re q uire me nts, w here 
a p plica ble, a n d t he I R B/ E C or st u d y  ce nter.
T he i n vesti gat or m ust e ns ure t hat eac h partici pa nt is f ull y i nf or me d a b o ut t he nat ure an 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 ua lit 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 ght t o access a n d c orrect t heir pers o nal data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of 
t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o s i g n t he I CD.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I R B/ E C-a p pr o ve d I CD (s) 
d uri n g t heir partici pati o n i n t he st u d y as re q uire d per l ocal re g ulati o ns.
A c o p y of t he I C D (s) m ust be pr o vi de d t o t he partici pa nt.
Partici pa nts w h o are rescree ne d are re q uire d t o si g n a ne w I C D.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 0
1 0. 1. 3. 1. Electr o nic C o nse nt 
Partici pa nts ma y  be a ble t o e x perie nce t he i nf or me d c o nse nt pr ocess b y electr o nic mea ns 
(e C o nse nt). T he e C o nse nt pr ocess i ncl u des a n electr o nic prese ntati o n of t he i nf or me d 
c o nse nt d oc u me nt (eI C D), cli nical trial e d ucati o nal c o m p o ne nts (as a p plica ble), a n d 
electr o nic si g nat ures (if all o we d b y  l ocal re g ulati o ns). T he use of e C o nse nt d oes n ot re place 
or alter t he I C D c o nte nt or i nf or me d c o nse nt pr ocess as descri be d a b o ve. T he e C o nse nt 
pr ocess c o m plies wit h a p plica ble re g ulati o ns a n d s p o ns or p olicies t o e ns ure relia bilit y  a n d 
data pri vac y . 
1 0. 1. 4. D at a Pr otecti o n
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of partici pa nt data.
Partici pa nts’ pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte d electr o nic a n d/ or pa per 
f or m a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y  
a ut h orize d st u d y staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site will be res p o nsi ble f or 
deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g breac h 
n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, partici pa nts will be assi g ne d a si n gle, par tici pa nt-s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y  t his si n gle, partici pa nt -s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nt s w h o partici pate d i n t he st u d y, li n ki n g eac h 
partici pa nt ’s n u merical c o de t o t heir act ual i de ntit y a n d me dical rec or d I D. I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he cli nical st u d y agree me nt a n d a p plica ble pri vac y  la ws.
I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are 
sec ure d by t ec h nical a n d or ga nizati o nal sec urit y m eas ures desi g ne d t o pr otect s uc h data 
a gai nst acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access.
T he s p o ns or mai ntai ns S O Ps o n h o w t o res p o n d i n t he e ve nt of u na ut h or ize d access, use, or 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 0. 1. 5. C o m mittees Str uct ure
1 0. 1. 5. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use an E- D M C.
1 0. 1. 6. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y results 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 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 1
w w w. pfizer .c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
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 ons 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 pl ica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts i ncl u de d 
i n mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y d oc u me nts a n d C S Rs 
i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A P s. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt hs after st u d y  c o m pleti o n. Partici pa nt -le vel data will be a n o ny m ize d i n acc or da nce 
wit h a p plica ble pri vac y  la ws a n d re g ulati o ns. C S Rs will ha ve pers o nally i de ntifia ble 
inf 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 nfl icts 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.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 2
1 0. 1. 7. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi gnee 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.
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 vest i gat or m ust per mit st u d y-relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce rec or ds a n d d oc u me nts.
T his verificati o n ma y  als o occ ur after st u d y c o m pleti o n. It is i m p orta nt t hat t he 
i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d 
p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he pr ocess .
M o nit ori n g details descri bi n g strate g y , i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d 
pr ocesses (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y , s uc h as ris k m a na ge me nt a n d 
m iti gati o n strate gies a n d anal yt ical ris k- base d m o nit ori n g), met h o d s, res p o nsi bilities, a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n mai ntai ne d 
a n d utilize d b y t he s p o ns or or desi g nee.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C D s, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y  be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
dat a 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 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 3
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 vide 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.
1 0. 1. 8. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nts are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are fr o m s o urce d oc u me nts m ust be 
c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d . T he 
i n vesti gat or ma y nee d t o re q uest pre vi o us me dical rec or ds or tra nsfer rec or ds, de pe n di n g o n 
t he st u d y. Als o, c urre nt me dical rec or ds m ust be a vaila ble.
Defi niti o n of w hat c o nstit utes a s o urce d oc u me nt a n d its ori gi n ca n be f o u n d i n t he S o urce 
D oc u me nt L ocat or , w hic h is mai ntai ne d b y t he s p o ns or’s desi g nee ( Pfizer C R U) .
Descri pti o n of t he use of t he c o m p uterize d s yste m is d oc u me nte d i n t he Data Ma na ge me nt 
Pla n , w hic h is mai ntai ne d b y t he s p o ns or’s desi g nee ( Pfizer C R U).
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce rec or d) t hat s u p ports t he 
i nf or mati o n e ntere d i n t he C R F.
T he s p o ns or or desi g nee will perf or m m o nit ori n g t o c o nfir m t hat data e ntere d i nt o t he C R F 
b y  a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; 
t hat t he safety a n d ri g hts of part ici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 9. Use of Me dic al Rec or ds
I n certai n sit uati o ns, s p o ns or re vie w of re dacte d c o pies of partici pa nt me dical rec or ds f or 
treat me nt of a n A E m a y  be perf or me d, w here et hicall y a n d scie ntificall y j ustifie d a n d 
per mitte d b y  l ocal re g ulati o ns, t o e ns ure partici pa nt safety. 
D ue t o t he p ot e ntial f or a partici pa nt t o be re -i de ntifie d fr o m t heir me dical rec or ds, t he 
f oll o wi n g acti o ns m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee:

T he i n vesti gat or or site staff m ust re dact pers o nal i nf or mati o n fr o m t he me dical 
rec or d. T he pers o nal i nf or mati o n i ncl u des, b ut is n ot li mite d t o, t he f oll o wi n g:  
partici pa nt na mes or i nitials , partici pa nt dates (e g, birt h date, date of h os pital 
a d missi o n/ disc har ge, date of deat h), partici pa nt i de ntificati o n n u m bers (e g, S ocial 
Sec urit y  n u m ber, healt h i ns ura nce n u m ber, me dical rec or d n u m ber, 
h os pital/i nstit uti o n i de ntifier), p artici pa nt l ocati o n i nf or mati o n (e g, street a d dress, 
cit y, c o u ntr y, p ostal c o de, IP a d dress), partici pa nt c o ntact i nf or mati o n (e g, 
tele p h o ne/fa x n u m ber, e mail a d dress).
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 4

Eac h me dical rec or d m ust be tra ns mitte d t o t he s p o ns or or s p o ns or desi g nee usi n g 
s yste ms wit h tec h nical a n d or ga nizati o nal sec urit y meas ures t o e ns ure t he pr otecti o n 
of pers o nal data (e g, Fl ore nce is t he preferre d s ys te m if a vaila ble). 
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. 1 0. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or , i ncl u di n g ( b ut n ot li mite d t o) 
re g ulat or y a ut h ority decisi o n, c ha n ge i n o pi ni o n of t he I R B/ E C, or c ha n ge i n be nefit -ris k 
assess me nt . St u d y  sites will be cl ose d u p o n st u d y co 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 g at or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or ’s pr oce d ures, or t he I CH G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt .
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 1 1. P u blic ati o n P olic y
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns. 
Pfizer will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he i n vesti gat or’s partici pati o n i n t he 
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P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 5
pre parati o n of t he pri mar y c o n gress a bstract, p oster, prese ntati o n, o r pri mar y ma n uscri pt f or 
t he st u d y.
I n vesti gat ors are free t o p u blis h i n di vi d ual ce nter res ults t hat t he y dee m t o be cli nicall y 
mea ni n gf ul after p u blicati o n of t he o verall res ults of t he st u d y  or 1 2 m o nt hs after pri mar y 
c o m pleti o n date or st u d y c o m pleti o n at all sites, w hic he ver occ urs first, s u bject t o t he ot her 
re q uire me nts descri be d i n t his secti o n.
T he i n vesti gat or will pr o vi de Pfizer a n o p p ort u nit y  t o re vie w a n y pr o p ose d p u blicati o n or 
a n y ot her ty pe of discl os ure of t he st u d y res ults (c ollecti vel y, “ p u blicati o n”) bef ore it is 
s u b mitte d or ot her wise discl ose d a n d will s u b mit all p u blicati o ns t o Pfizer 3 0 da y s bef ore 
s u b missi o n. If a ny pate nt acti o n is re q uire d t o pr otect i ntellect ual pr o pert y ri g hts, t he 
i n vesti gat or a grees t o dela y t he discl os ure f or a peri o d n ot t o e xcee d a n a d diti o nal 6 0 da y s 
u p o n re q uest fr o m Pfizer. T his all o ws Pfizer t o pr otect pr o prietar y  i nf or mati o n a n d t o pr o vi de 
c o m me nts, a n d t he i n vesti gat or will, o n re q uest, re m o ve a n y pre vi o usl y u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore di scl os ure, e xce pt f or a n y st u d y-i nter ve nti o n or  
Pfizer -relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults. F or j oi nt p u blicati o ns, s h o ul d t here be disa gree me nt 
re gar di n g i nter pretati o n a n d/ or prese ntati o n of s pecific a nalys is res ults, res ol uti o n of, a n d 
res p o nsi bilit y f or, s uc h disa gree me nts will be t he c ollecti ve res p o nsi bilit y of all a ut h ors of 
t he p u blicati o n.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or a n d Pfizer will c o m pl y w it h 
rec o g nize d et hical sta n dar ds c o ncer ni n g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose 
esta blis he d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. T he i n vesti gat or will 
discl ose a n y relati o ns hi p wit h Pfizer a n d a n y rele va nt p ote ntial c o nflicts of i nterest, i ncl u di n g 
a n y fi na ncial or pers o nal relati o ns hi p wit h Pfizer, i n a n y p u blicati o ns. All a ut h ors will ha ve 
access t o t he rele va nt statistical ta bles, fi g ures, a n d re p orts (i n t heir ori gi nal f or mat) re q uire d 
t o de vel o p t he p u blicati o n.
1 0. 1. 1 2. S p o ns or’s Me dic all y Q u alifie d I n di vi d u al
T he c o ntact i nf or mati o n f or t he s p o ns or ’s M QI
f or t he st u d y is d oc u me nte d i n t he st u d y 
c o ntact list, l ocate d i n t he cli nical trial ma na ge me nt s y ste m. 
T o facilitate access t o t heir i n vesti gat or a n d t he s p o ns or’s M QI f or st u dy- relate d me dical 
q uesti o ns or pr o ble ms fr o m n o n-st u d y healt hcare pr ofessi o nals, partici pa nts are pr o vi de d 
wit h a n E C C at t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr ot oc ol 
a n d st u d y i nter ve nti o n i de ntifiers, ( b) partici pa nt’s st u d y i de ntificati o n n u m ber, (c) site 
e mer ge nc y p h o ne n u m ber acti ve 2 4 h o urs/ da y, 7 da ys per wee k.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he partici pa nt a n d t heir i n vesti gat or a n d site staff, a n d bet wee n t he i n vesti gat or a n d 
s p o ns or st u d y tea m. T he E C C is o nl y t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n 
t he researc h st u dy, as a mea ns of reac hi n g t he i n vesti gat or or site staff relate d t o t he care of a 
partici pa nt. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 6
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 y pe 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 ud y  t o assess a ny percei ve d safet y iss ues.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 7 8
T a ble 5 .
Pr ot oc ol -Re q uire d L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
a.
C ystati n C ( Sc ys): Scree ni n g or Baseli ne Sc ys is rec o m me n de d t o hel p differe ntiate p ost-baseli ne DI KI 
fr o m DI CI. P ost- baseli ne, Sc ys is meas ure d if a n d o nl y if ser u m creati ni ne i ncrease p ost -baseli ne is o bser ve d 
(see Secti o n 7. 1. 1 ).
b.
Scree ni n g , Baseli ne a n d P ost -baseli ne ( o nl y i n case of refle x meas ure me nt of Sc ys) e G F Ris calc ulate d 
usi n g 2 0 2 1 C K D -E PI e G F R (c o m bi ne d Screat a n d Sc ys - base d) e q uati 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.
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 .
e.
T he mi ni m u m re q uire m e nt f or dr u g scree ni n g i ncl u des c oca ine, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot hers are site - a n d st u d y-s pecific).
f.
Test as refle x if H Bs A g a n d/ or H Bc A b are p ositi ve .
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.
La b orat or y /a nalyt e res ults t hat c o ul d u n bli n d t he st u d y  a n d ha ve bee n c ollecte d f or t he 
p ur p ose of t he st u d y will n ot be re p orte d t o i n vesti gat or sites or ot her bli n de d pers o n nel u ntil 
t he st u d y has bee n u n bli n de d.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical safety la b orat or y 
meas ure me nts at baseli n e a n d at all ti mes after d ose a d mi nistrati o n ma y  be retai ne d a n d 
st ore d f or t he d urati o n of t he st u d y. U p o n c o m pleti o n of t he st u d y, t hese retai ne d safet y 
sa m ples ma y be use d f or t he assess me nt of e x pl orat or y safety bi o mar kers or u ne x pecte d 
safety fi n di n gs. T hese data will n ot be i ncl u de d i n t he C S R. Sa m ples t o be use d f or t his 
p ur p ose will be s hi p pe d t o eit her a Pfizer -a p pr o ve d B B S facilit y or ot her desi g nate d 
la b orat or y a n d retai ne d f or u p t o 1 ye ar f oll o wi n g t he c o m pleti o n of t he st u d y .
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 0
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 Es. 
If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he 
e ve nt is seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was 
necessar y , t he A E s h o ul d be c o nsi dere d seri o us.
H os pitalizati o n f or electi ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 1
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:
d.
Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T hi s defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vely mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle), t hat m a y  i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nit al a n o m al y/ birt h defect
f.
Is a s us pecte d tr a ns missi o n vi a a Pfizer pr o d uct of a n i nfecti o us a ge nt, 
p at h o ge nic or n o n -p at h o ge nic 
T he e ve nt ma y  be s us pecte d fr o m cli nical sy m pt o ms or l a b orat or y fi n di n gs 
i n dicati n g a n i nfecti o n i n a partici pa nt e x p ose d t o a Pfizer pr o d uct. T he ter ms 
“s us pecte d tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d s y n o n y m o us. T hese 
cases are c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y 
p har ma c o vi gila nce pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o priate.
g.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d b y  t he i n vesti gat or i n deci di n g 
w het her S A E re p orti n g is a p pr o priate i n ot her sit uati o ns, s uc h as si g nifica nt 
me dical e ve nts t hat ma y je o par dize t he partici pa nt or ma y  re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y  be c o nsi dere d seri o us.

E xa m p les of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d 
d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of 
dr u g de pe n de nc y  or dr u g a b use.
1 0. 3. 3. Defi niti o n of S A R
S A R D efi niti o n

S A R s are all n o xi o us a n d u ni nte n de d res p o nses t o a n I M P relate d t o a n y d ose 
a d mi nistere d t hat res ult i n deat h, are life -t hreate ni n g, re q uire i n patie nt 
h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n, res ult i n persiste nt or 
si g nifica nt disa bilit y or i nca pacit y, or are a c o n ge nital a n o mal y or birt h defect.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 2
1 0. 3. 4. Defi niti o n of S U S A R
S U S A R Defi niti o n

S U S A R is a S A R w h ose nat ure, se verit y or o utc o me is n ot c o nsiste nt wit h t he 
refere nce safety i nf or mati o n.
1 0. 3. 5. 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 or via P S S A 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 ty pes 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 pos ure. 
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 / P S S A f or re p orti n g of S A E i nf or mati o n 
is n ot t he sa me as t he A E pa ge of t he C R F. W he n t he sa me data are c ollecte d, t he f or ms 
m ust be c o m plete d i n a c o nsiste nt ma n ner. A 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 / P S S A 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 / PS S A t o 
Pfizer S afet y Wit hi n 2 4 
H o urs of A w are ness
S A E
All
All
N o nseri o us A E
All
N o ne
E x p os ure t o t he st u d y 
i nter ve nti o n u n der st u d y 
d uri n g pre g na nc y  or 
breastfee di n g
All A E s/ S A Es ass ociate d 
wit h E D P or E D B
N ote: I nsta nces of E D P or 
E D B n ot ass ociate d wit h a n 
A E or S A E are n ot ca pt ure d 
i n t he C R F
All i nsta nces of E D P are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) *
All i nsta nces of E D B are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) * *
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 3
A E a n d S A E Rec or di n g / Re p orti n g
E n vir o n me ntal or 
occ u pati o nal e x p os ure 
t o t he pr o d uct u n der 
st u d y t o a 
n o n partici pa nt ( n ot 
i n v ol vi n g E D P or E D B)
N o ne. E x p os ure t o a st u d y 
n o n - partici pa nt is n ot 
c ollecte d o n t he C R F
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
rep orte d * * *
*
E D P ( wit h or wit h o ut a n ass ociate d S A E): is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort 
F or m a n d E D P S u p ple me ntal F or m or via P S S A . 
* * 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 or P S S A , 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 wit 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 or via P S S A . 

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 o r 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.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by Pfizer Safet y . I n t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0. 1. 9 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis 
( n ot t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E or S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: A t y pe of A E t hat is us uall y  tra nsie nt a n d ma y re q uire o nl y mi ni mal 
treat me nt or t hera pe utic i nter ve nti o n. T he e ve nt d oes n ot ge nerall y i nterfere wit h 
us ual A D L .

M o derate: A t y pe of A E t hat is us uall y  alle viate d wit h a d diti o nal s pecific 
t hera pe utic i nter ve nti o n. T he e ve nt i nterferes wit h us ual A D L , ca usi n g 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 4
A E a n d S A E Rec or di n g / Re p orti 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.

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.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 5
Assess me nt of C a us alit y

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 / P S S A 
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 mat i o n will be rec or de d i n t he ori gi nall y s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 
h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 6. Re p orti n g of S A E s
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D C T

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic D C T (e g, e S A E or P S S A) .

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E 
re p ort f or m (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic D C T (e g, e S A E or P S S A) or 
pa per f or m (as a p plica ble) as s o o n as t he data bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic D C T will be ta ke n 
off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 6

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves 
u p date d data o n a pre vi o usl y  re p orte d S A E after t he electr o nic D C T has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a t he C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is o ne of t he met h o d s t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y .

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, a n alter nati ve met h o d s h o ul d 
be use d, e g, sec ure d ( Tra ns p ort L a yer Sec urit y) or pass w or d-pr otecte d e mail. I f 
n o ne of t hese met h o ds ca n be use d, n otificati o n b y tele p h o ne is acce pta ble wit h a 
c o p y of t he C T S A E Re p ort F or m se nt by o ver ni g ht mail or c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 7
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 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 safet y ris k of t he st u d y 
i nter ve nti o n(s): 

Refrai n fr o m d o nati n g s per m .
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse as t heir prefe rre d a n d us ual lifest yle 
(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 hl y 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 a le 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 is n ot pre g na nt or breastfee di n g a n d is n ot 
a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n earl y u n detecte d 
pre g na nc y .
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 8
If fertilit y is u nclear (e g, a me n orr hea or oli g o me n 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 y sterect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a me dical ca use ot her t ha n t he a b o ve
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site pers o n nel’s 
re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y 
i nter vie w. T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he partici pa nt’s me dical 
rec or d f or t he st u dy.
2.
P ost me n o pa usal fe male .

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A h i g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars ol d a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A f e male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o  
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.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 8 9
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat H a ve L o w User De pe n de nc y (f or W O C B P part ners of male 
partici pa nts)
1.
I m pla nta ble pr o gest o ge n -o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
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 (f or W O C B P part ners of male 
partici pa nts) 
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n:

Oral + b arrier*

I ntra va gi nal + b arrier*

Tra ns d er mal + barrier*
7.
Pr o gest o ge n - o nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral + b arrier*

I njecta ble + b arrier*
Se x ual A bsti ne nce
8.
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y  a n d t he preferre d a n d us ual lifestyl e of t he 
partici pa nt
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 0
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o ns 6 or 7 f or t he st u dy 
i ncl u de a ny of t he f oll o wi n g:

Male or fe male c o n d o m, wit h or wit h o ut s per mici de;

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 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 1
1 0. 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 nalys 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 a nal yze d as part of a m ultist u d y assess me nt of ge netic fact ors 
i n v ol ve d i n t he res p o nse t o st u d y i nter ve nti o n or st u d y i nter ve nti o ns of t his class t o 
u n dersta n d treat me nts f or t he disease(s) u n der st u d y  or t he disease(s) t he msel ves.

T he res ults of ge netic a nal y ses ma y be re p orte d i n t he C S R or i n a se parate st u d y 
s u m mar y, or ma y be use d f or i nter nal decisi o n ma ki n g wit h o ut bei n g i ncl u de d i n a 
st u d y re p ort.

T he s p o ns or will st ore t he D N A sa m ples i n a sec ure st ora ge s pace wit h a de q uate 
meas ures t o pr otect c o nfi de ntialit y . 

T he sa m ples will be retai ne d as i n dicate d:

Sa m ple f or s pecifie d ge netic a nal ys is (see S ecti o n 8. 6. 1 ) will be st ore d f or u p t o 1 5 
ye ars or ot her peri o d as per l ocal re q uire me nts. 

Sa m ples f or ge netic researc h will be la bele d wit h a c o de. T he ke y  bet ween t he c o de 
a n d t he partici pa nt ’s pers o nall y i de ntif yi n g i nf or mati o n (e g, na me, a d dress) will be 
hel d sec urel y at t he st u d y site.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 3
T he partici pa nt s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults. T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt. 
I n a d diti o n t o re peati n g meas 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 pa rate 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 alternati ve eti ol o g y .
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 4
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 est i 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 onfir 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 c alc 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 by c o m bi ne d Screat pl us Sc ys -base d e q uati o n. W he n p ost -baseli ne 
Screat i ncrease ≥0. 3 m g/ d L  is c o nfir me d, t he n refle x Sc ys meas ure me nt is nee de d t o e na ble 
p ost -baseli ne c o m par is o n of e G F R c ha n ges ( Screat o nl y- base d e G F R a n d c o m bi ne d Screat 
pl us Sc y s e G F R). 
1 0. 7. 2. A ge -S pecific Ki d ne y F u ncti o n C alc ul ati o n Rec o m me n d ati o ns
1 0. 7. 2. 1. A d ults ( 1 8 Y e ars a n d A b o ve) — 2 0 2 1 C K D- E P I E q u ati o ns
e G F R ( m L/ mi n/ 1. 7 3 m²) 2 3
2 0 2 1 C K D -
E PI            
Scr e at O nl y
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤
0. 7
N A
e G F R = 1 4 3 × ( Scr eat/ 0. 7)-0. 2 4 1  ×  ( 0. 9 9 3 8) A ge
Fe male
if > 0. 7
N A
e G F R = 1 4 3 × ( Scr eat/ 0. 7)-1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
Male
if ≤
0. 9
N A
e G F R = 1 4 2 × ( Scr eat/ 0. 9)-0. 3 0 2  ×  ( 0. 9 9 3 8) A ge
Male
if > 0. 9
N A
e G F R = 1 4 2 × ( Scr eat/ 0. 9)-1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI           
Scr e at-Sc ys 
C o m bi ne d
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤
0. 7
if ≤
0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Fe male
if ≤
0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Fe male
if > 0. 7
if ≤
0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Fe male
if > 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Male
if ≤
0. 9
if ≤
0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Male
if ≤
0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  × ( Sc ys/ 0. 8) -0. 7 7 8  × ( 0. 9 9 6 1) A ge
Male
if > 0. 9
if ≤
0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×  ( Sc ys/ 0. 8) - 0. 3 2 3  × ( 0. 9 9 6 1) A ge
Male
if > 0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×  ( Sc ys/ 0. 8) - 0. 7 7 8  × ( 0. 9 9 6 1) A ge
1 0. 7. 3. Ki d ne y F u ncti o n C alc ul ati o n T o ols
T he s p o ns or has pr o vi de d t he f oll o wi n g res o urces t o i n vesti gati o nal sites w he n re q uired t o 
calc ulate a ge -s pecific ki d ne y f u ncti o n at Scree ni n g, Baseli ne, a n d p ost-Baseli ne visits. Site 
calc ulati o ns of ki d ne y f u ncti o n ca n be perf or me d ma n uall y, usi n g t he a ge a p pr o priate 
f or m ulae (see Secti o n 1 0. 7. 2 ) a n d ca n use rec o m me n de d o nli ne ki d ne y f u ncti o n calc ulat ors 
t o re d uce t he li keli h o o d of a calc ulati o n err or. 
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 7

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) .

V e ntric ular rh y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (H R
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m [s uc h as
torsa des de p oi ntes ]).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d- de gree) h eart b l oc k.
E C G Fi n di n gs T h at Q u alif y as S A Es

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n .

S ustai ne d v e ntric ular ta c h yarr h yt h mias ( > 3 0-sec o n ds d urati o n).

Sec o n d - or t hir d -de gree A V bl oc k re q uiri n g pace ma ker place me nt .

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n .

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h y t 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 re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 9 9
I n a sit u ati o n w here a p pr o pri ate me dic al c are of a p artici p a nt re q uires t he use of a pr o hi bite d 
 
: T hese me dicati o ns are n ot per mitte d i n t he st u d y e xce pt i n e mer ge nc y sit uati o ns re q uiri n g n o m ore t ha n o ne 
da y of a d mi nistrati o n. T o pical a p plicati o n of a nti micr o bial a n d a ntif u n gal me dicati o ns i s per mitte d. 
T his list of dr u gs pr o hi bite d f or p ote ntial D DI c o ncer ns ma y be re vise d d uri n g t he c o urse of 
t he st u d y wit h writte n n otificati o n fr o m s p o ns or, t o i ncl u de or e xcl u de s pecific dr u gs or dr u g 
cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or t he I M P, a vaila bilit y  of ne w 
i nf or mati o n i n literat ure o n t he D DI p ote ntial of ot her dr u gs), if t he o verall be nefit:ris k 
assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y i m pact t he safet y of 
partici pa nts or t he sci e ntific val ue of t he trial.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 0
1 0. 1 0. A p pe n di x 1 0 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Ter m
A 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verit y sta n dar dizati o n)
A bs
a bs ol ute
A C C
acet yl -C o A car b o x yl ase
A D L
acti vit y/ acti vities of dail y li vi n g
A D P
a de n osi ne di p h os p hate
A E
a d verse e ve nt
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A M P
a de n osi ne m o n o p h os p hate
A M P K
A M P -acti vate d pr otei n ki nase
A M P K 
5’- A M P -acti vate d pr otei n ki nase s u b u nit ga m ma- 3
A N O V A
a nal ys is of varia nce
A S T
as partate a mi n otra nsferase
A T P
A de n osi ne tri p h os p hate
A U C
area u n der t he c o nce ntrati o n-ti me c ur ve
A U C 2 4
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4 h o urs
A U C i nf
area u n der t he c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o i nfi nit y
A U C i nf( d n)
d ose n or malize d A U C i nf
A U C last
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m 0 t o ti me of last 
meas ura ble c o nce ntrati o n
A U C last( d n)  
d ose n or malize d A U C last
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
B B S
Bi os peci me n Ba n ki n g S yste m
B MI
b o d y  mass i n de x
B P
bl o o d press ure
b p m
beats per mi n ute
C eff
Efficaci o us c o nce ntrati o n
C F R
C o de of Fe deral Re g ulati o ns
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
c hr o nic ki d ne y disease e pi de mi ol o g y
C L / F
a p pare nt cleara nc e
C last
t he pre dicte d plas ma c o nce ntrati o n at t he last q ua ntifia ble ti me p oi nt 
esti mate d fr o m t he l o g-li near re gressi o n a nalys is
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C ma x ( d n)
d ose -n or malize d C ma x
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI


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


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 2
A b bre vi ati o n
Ter m
H b
he m o gl o bi n
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C V A b
he patitis C a nti b o d y
H E K
h u ma n e m br y o nic ki d ne y
H F p E F
heart fail ure wit h preser ve d ejecti o n fracti o n
HI V
h u ma n i m m u n o deficie nc y vir us
h KI
h u ma nize d k n oc k -i n
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
I n vesti gat or’s Br oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical 
Re q uire me nts f or P har mace uticals f or H u ma n Use
I D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal Ne w Dr u g 
I N R
i nter nati o nal n or malize d rati o
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I RB
I nstit uti o nal Re vie w B oar d
I V
I ntra ve n o us(ly)
K 2E D T A
di p otassi u m et h y le ne dia mi netetraacetic aci d
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
K D O QI
Ki d ne y  Disease O utc o mes Q ualit y Initiati ve
kel
first-or der eli mi nati o n rate c o nsta nt
KI  
k n oc ki n
K O
k n oc k o ut
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 C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M QI
me dicall y  q ualifie d i n di vi d ual
N A
n ot a p plica ble
N C
n ot calc ulate d
N D
n ot d o ne
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o o bser ve d a d verse effect le vel
N O E L
n o o bser ve d effect le vel
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 3
A b bre vi ati o n
Ter m
N S
n o sa m ple
O C T
or ga nic cati o n tra ns p orter
P b o
place b o
P D
p har mac o d y n a mic(s)
P E
P h y sical E xa mi nati o n
P G x 
p har mac o ge n o mic(s)
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic(s)
P O
b y  m o ut h
P R
p ulse rate
P S S A
Pfizer's Seri o us A d verse E ve nt S u b missi o n Assista nt
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
R R
res pirat or y rate
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
S A R
Seri o us A d verse Reacti o n
S C
s u bc uta ne o us
Screat
ser u m creati ni ne 
Sc y s
ser u m c ystati n C
S D D
s pra y drie d dis persi o n
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
Si n gle Refere nce Safet y  D oc u me nt
S U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n
t½
ter mi nal p hase half-life
T bili
t otal bilir u bi n
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me t o reac h Cma x
U A C R
uri ne al b u mi n/creati ni ne rati o
U G T
uri di ne 5’ -di p h os p h o -gl uc ur o n os yl tra nsferase
U L N
u p per li mit of n or mal
U S
U nite d States
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI
C CI
C CI
C CI
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 4
A b bre vi ati o n
Ter m
U TI
uri nar y  tract i nfecti o n
V O 2
o x y ge n c o ns u m pti o n
Vz/ F
a p pare nt v ol u me of distri b uti o n f or e xtra vasc ular d osi n g
W B C
w hite bl o o d cell
W O C B P
w o ma n/ w o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)
C CI


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 5
1 1. R E F E R E N C E S
1
Ti m mis A, T o w nse n d N, Gale C, et al. E ur o pea n S ociet y  of Car di ol o g y: Car di o vasc ular 
Disease Statistics 2 0 1 7. E ur o pea n Heart J o ur nal 2 0 1 8; 3 9: 5 0 8 - 7 9.
2
Bra gazzi N L , Z h o n g W, S h u J, et al. B ur de n of heart fail ure a n d u n derl y i n g ca uses i n 
1 9 5 c o u ntries a n d territ ories fr o m 1 9 9 0 t o 2 0 1 7. E ur o pea n J o ur nal of Pre ve nti ve 
Car di ol o g y , 2 0 2 1; 2 8: 1 6 8 2- 9 0.
3
Be nja mi n EJ, M u nt ner P, Al o ns o A, et al. Heart Disease a n d Str o ke Statistics - 2 0 1 9 
U p date A Re p ort Fr o m t he A merica n Heart Ass ociati o n. Circ ulati o n, 2 0 1 9; 1 3 9: E 5 6 -
E 5 2 8.
4
D u nla y  S M, R o ger V L, a n d M. M. Re dfiel d. E pi de mi ol o g y of heart fail ure wit h 
preser ve d ejecti o n fracti o n. Nat Re v Car di ol, 2 0 1 7; 1 4: 5 9 1- 6 0 2.
5
T uc ker WJ, Nels o n M D, Bea u dr y  RI, et al. I m pact of E xercise Trai ni n g o n Pea k O x yge n 
U pta ke a n d its Deter mi na nts i n Heart Fail ure wit h Preser ve d Ejecti o n Fracti o n. Car d 
Fail Re v 2 0 1 6; 2: 9 5 -1 0 1.
6
N a y or M, H o ustis N E, Na masi va y a m M, et al. I m paire d E xercise T olera nce i n Heart 
F ail ure Wit h Preser ve d Ejecti o n Fracti o n: Q ua ntificati o n of M ulti or ga n S y ste m Reser ve 
Ca pacit y . J A C C Heart Fail 2 0 2 0; 8: 6 0 5- 1 7.
7
Wi nzer, E. B., A. A u gstei n, A. Sc ha uer, et al. I m pact of Differe nt Trai ni n g M o dalities 
o n M olec ular Alterati o ns i n S keletal M u scle of Patie nts Wit h Heart Fail ure Wit h 
Preser ve d Ejecti o n Fracti o n: A S u bst u d y  of t he O pti m E x Trial. Circ Heart Fail 2 0 2 2; 1 5: 
e 0 0 9 1 2 4.
8
Herzi g, S a n d S ha w RJ. A M P K: g uar dia n of meta b olis m a n d mit oc h o n drial 
h o me ostasis. Nat Re v M ol Cell Bi ol, 2 0 1 8; 1 9: 1 2 1 - 3 5.
9
Xia o B R, Heat h R, Sai u P, et al. Str uct ural basis f or A M P bi n di n g t o ma m malia n A M P -
acti vate d pr otei n ki nase. Nat ure 2 0 0 7; 4 4 9: 4 9 6- 5 0 0.
1 0
Carli n g D, Za m mit V A, Har die D G. A C o m m o n Bic y clic Pr otei n-Ki nase Casca de 
I nacti vates t he Re g ulat or y E nz ymes o f Fatt y- Aci d a n d C h olester ol-Bi os y nt hesis, Fe bs 
Letters, 1 9 8 7; 2 2 3: 2 1 7 -2 2.
1 1
Watt MJ, H ol mes A G, Pi n na ma ne ni S K, et al. Re g ulati o n of H S L  seri ne 
p h os p h or y lati o n i n s keletal m uscle a n d a di p ose tiss ue. A m J P h ysi ol E n d ocri n ol Meta b 
2 0 0 6; 2 9 0: E 5 0 0 - 8.
                                                
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)


P F -0 7 2 9 3 8 9 3
Pr ot oc ol C 5 1 7 1 0 0 1
Fi nal Pr ot o c ol A me n d me nt 1 , 0 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 6
                                                                                                                                                      
1 2
Sa ka m ot o K a n d H ol ma n G D. E mer gi n g r ole f or A S 1 6 0/ T B C 1 D 4 a n d T B C 1 D 1 i n t he 
re g ulati o n of G L U T 4 traffic. A merica n J o ur nal of P h ysi ol o g y-E n d ocri n ol o g y  a n d 
Meta b olis m 2 0 0 8; 2 9 5: E 2 9 -E 3 7.
1 3
Z o n g H, Re n J M, Y o u n g L H, et al. 2 0 0 2. A M P ki nase is re q uire d f or mit oc h o n drial 
bi o ge nesis i n s keletal m uscle i n res p o nse t o c hr o nic e ner g y de pri vati o n. Pr oc Natl Aca d 
Sci U S A 2 0 0 2; 9 9: 1 5 9 8 3 - 8 7.
1 4
Ja ger S, Ha n dsc hi n C, St-Pierre J, et al. A M P -acti vate d pr otei n ki nase ( A M P K) acti o n i n 
s keletal m uscle via direct p h os p h or ylati o n of P G C - 1al p ha. Pr oc Natl Aca d Sci U S A, 
2 0 0 7; 1 0 4: 1 2 0 1 7 - 2 2.
1 5
W ojtasze ws ki J F, Bir k J B, Fr osi g C, et al. 5' A M P acti vate d pr otei n ki nase e x pressi o n i n 
h u ma n s keletal m uscle: effects of stre n gt h trai ni n g a n d t y pe 2 dia betes. J P h y si ol, 2 0 0 5; 
5 6 4: 5 6 3 - 7 3.
1 6
Kj o bste d R, Hi n gst J R, Fe ntz J, et al. A M P K i n s keletal m uscle f u ncti o n a n d 
meta b olis m. F A S E B J, 2 0 1 8; 3 2: 1 7 4 1 - 7 7.
1 7
Ma hla p u u M, J o ha nss o n C, L i n d gre n K, et al. E x pressi o n pr ofili n g of t he ga m ma -
s u b u nit is of or ms of A M P-acti vate d pr otei n ki nase s u g gests a maj or r ole f or ga m ma 3 i n 
w hite s keletal m uscle. A m J P h y si ol E n d ocri n ol Meta b, 2 0 0 4; 2 8 6: E 1 9 4- 2 0 0.
1 8
Bir k J B a n d W ojtasze ws ki J F P. Pre d o mi na nt al p ha 2/ beta 2/ ga m ma 3 A M P K acti vati o n 
d uri n g e xercise i n h u ma n s keletal m uscle. J P h y si ol, 2 0 0 6; 5 7 7: 1 0 2 1- 3 2.
1 9
St ei n ber g G R a n d Carli n g D. A M P -acti vate d pr otei n ki nase: t he c urre nt la n dsca pe f or 
dr u g de vel o p me nt. Nat Re v Dr u g Disc o v, 2 0 1 9; 1 8: 5 2 7- 5 1.
2 0
M y ers R W, G ua n H P, E hr hart J, et al. S yste mic pa n -A M P K acti vat or M K -8 7 2 2 
i m pr o ves gl uc ose h o me ostasis b ut i n d uces car diac h ypertr o p h y . Scie nce, 2 0 1 7; 3 5 7: 
5 0 7- 1 1.
2 1
C ostf or d S R, Ka vaslar N, A hit u v N, et al. Gai n - of-f u ncti o n R 2 2 5 W m utati o n i n h u ma n 
A M P K ga m ma( 3) ca usi n g i ncrease d gl y c o ge n a n d decrease d tri gl yc eri de i n s keletal 
m uscle, P L o S O ne, 2 0 0 7; 2: e 9 0 3.
2 2
Cra wf or d S, C ostf or d S, A g uer C, et al. Nat urall y occ urri n g R 2 2 5 W m utati o n of t he 
ge ne e nc o di n g A M P -acti vate d pr otei n ki nase ( A M P K) ga m ma( 3) res ults i n i ncrease d 
o xi dati ve ca pacit y  a n d gl uc ose u pta ke i n h u ma n pri mar y m yot u bes. Dia bet ol o gia, 2 0 1 0; 
5 3: 1 9 8 6 - 9 7.
2 3
I n ker L A, E nea nya  N D, C ores h J, et al. Ne w Creati ni ne- a n d C ystati n C-Base d 
E q uati o ns t o Esti mate G F R wit h o ut Race. N E n gl J Me d. 2 0 2 1; 3 8 5( 1 9): 1 7 3 7 - 4 9.
0 9 0 1 7 7 e 1 9 d a b b 6 7 3\ A p pr o v e d\ A p pr o v e d O n: 0 7- J u n- 2 0 2 3 1 7: 0 0 ( G M T)

SAP_001.pdf: 
Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 of 2 7
Pr ot oc ol C 5 1 7 1 0 0 1
A P H A S E 1, R A N D O MI Z E D, D O U B L E- B LI N D, S P O N S O R -O P E N, P L A C E B O -
C O N T R O L L E D, 4 -P E RI O D, C R O S S O V E R, FI R S T -I N-H U M A N S T U D Y T O 
E V A L U A T E T H E S A F E T Y, T O L E R A BI LI T Y, A N D P H A R M A C O KI N E TI C S O F 
SI N G L E A S C E N DI N G O R A L D O S E S O F P F- 0 7 2 9 3 8 9 3 A D MI NI S T E R E D T O
H E A L T H Y A D U L T P A R TI CI P A N T S
St atistic al A n al ysis Pl a n 
( S A P)
Versi o n : 
2  
D ate:
2 1 Mar 2 0 2 4   
N ote:  Te xt ta ke n ver bati m fr o m t he pr ot oc ol is it alicize d i n t his d oc u me nt. 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 of 2 7
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 .....................................................................................................................4
LI S T O F FI G U R E S ...................................................................................................................4
A P P E N DI C E S ...........................................................................................................................4
1. V E R SI O N HI S T O R Y ............................................................................................................5
2. I N T R O D U C TI O N .................................................................................................................5
2. 1. M o dificati o ns t o t he A nal y sis Pla n Descri be d i n t he Pr ot oc ol..................................5
2. 2. St u d y  O bjecti ves, E n d p oi nts, a n d Esti ma n ds............................................................6
2. 3. St u d y  Desi g n.............................................................................................................7
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S ..................................................................................................................8
3. 1. Pri mar y  E n d p oi nt(s)..................................................................................................8
3. 1. 1. A d verse E ve nts .............................................................................................8
3. 1. 2. Cli nical Safet y  La borat or y  Tests..................................................................8
3. 1. 3. Vital Si g ns ....................................................................................................9
3. 1. 4. C o nti n u o us Car diac M o nit ori n g ...................................................................9
3. 1. 5. 1 2 -Lea d E C G ..............................................................................................1 0
3. 1. 6. P h y sical E xa mi nati o ns ................................................................................1 0
3. 1. 7. Ne ur ol o gical E xa mi nati o ns ........................................................................1 0
3. 2. Sec o n dar y  E n d p oi nt(s)............................................................................................1 1
3. 3. Ot her E n d p oi nt(s) ....................................................................................................1 2
3. 3. 1. A d diti o nal Plas ma P F -0 7 2 9 3 8 9 3 Para meters .............................................1 2
3. 3. 2. Plas ma P F -0 7 2 9 3 8 9 3 P K para meters d uri n g cr y stalli ne f or m peri o d 
if c o n d ucte d......................................................................................................1 3
3. 3. 3. Tra ns p orter bi o mar kers ( o pti o nal) ..............................................................1 3
3. 4. Baseli ne Varia bles ...................................................................................................1 3
3. 5. Safet y E n d p oi nts .....................................................................................................1 3
4. A N A L Y SI S S E T S ( P O P U L A T I O N S F O R A N A L Y SI S)................................................... 1 3
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S ....................................................1 4
5. 1. H y p ot heses a n d Decisi o n R ules ..............................................................................1 4
5. 2. Ge neral Met h o ds .....................................................................................................1 4
5. 2. 1. A nal y ses f or C o nti n u o us E n d p oi nts ...........................................................1 4
5. 2. 2. A nal yses f or Cate g orical E n d p oi nts ...........................................................1 5
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 3 of 2 7
5. 2. 3. Mi xe d Effect M o del ....................................................................................1 5
5. 3. Met h o ds t o Ma na ge Missi n g Data ..........................................................................1 5
5. 3. 1. Missi n g Safet y Data ....................................................................................1 5
5. 3. 2. Missi n g P K C o nce ntrati o n Data................................................................. 1 5
5. 3. 3. Missi n g Plas ma P K Para meters ..................................................................1 6
6. A N A L Y S E S A N D S U M M A RI E S ......................................................................................1 6
6. 1. Pri mar y  E n d p oi nt(s)................................................................................................1 6
6. 1. 1. A d verse E ve nts ...........................................................................................1 6
6. 1. 2. Cli nical Safe t y La b orat or y Tests................................................................1 7
6. 1. 3. Vital Si g ns ..................................................................................................1 7
6. 1. 4. C o nti n u o us Car diac M o nit ori n g .................................................................1 7
6. 1. 5. 1 2 -Lea d E C G ..............................................................................................1 8
6. 1. 6. P h y sical E xa mi nati o ns ................................................................................1 8
6. 1. 7. Ne ur ol o gical E xa mi nati o ns ........................................................................1 9
6. 2. Sec o n dar y  E n d p oi nt(s)............................................................................................1 9
6. 3. Ot her E n d p oi nts .......................................................................................................2 0
6. 3. 1. A d diti o nal Plas ma P F -0 7 2 9 3 8 9 3 Para meters .............................................2 0
6. 3. 2. Plas ma P F -0 7 2 9 3 8 9 3 P K para meters d uri n g cr y stalli ne f or m peri o d 
if c o n d ucte d......................................................................................................2 1
6. 3. 3. Tra ns p orter bi o mar kers ( o pti o nal) ..............................................................2 1
6. 4. S u bset A nal y ses.......................................................................................................2 1
6. 5. Bas eli ne a n d Ot her S u m maries a n d A nal ys es .........................................................2 2
6. 5. 1. Baseli ne S u m maries ....................................................................................2 2
6. 5. 2. St u d y  C o n d uct a n d Partici pa nt Dis p ositi o n................................................2 2
6. 5. 3. St u d y  Treat me nt E x p os ure .........................................................................2 2
6. 5. 4. C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts.................................. 2 2
6. 5. 5. S pecifie d Ge netics ......................................................................................2 2
6. 5. 6. Ot her E x pl orat or y  Bi o mar kers ...................................................................2 2
6. 6. Safet y S u m maries a n d A nal yses .............................................................................2 2
7. I N T E RI M A N A L Y S E S .......................................................................................................2 2
7. 1. I ntr o d ucti o n .............................................................................................................2 2
7. 2. I nteri m A nal ys es a n d S u m maries ............................................................................2 3
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 4 of 2 7
A P P E N DI C E S .........................................................................................................................2 4
LI S T O F T A B L E S
Ta ble 1.
S u m mar y  of C ha n ges..................................................................................5
Ta ble 2.
Plas ma P F -0 7 2 9 3 8 9 3 P K Para meters .......................................................1 1
Ta ble 3.
A d diti o nal P F -0 7 2 9 3 8 9 3 P K Para meters ..................................................1 2
Ta ble 4. 
S u m mar y  Statistics f or P F- 0 7 2 9 3 8 9 3 Plas ma P K Para meters .................1 9
Ta ble 5.
S u m mar y  Statistics f or A d diti o nal P F-0 7 2 9 3 8 9 3 Plas ma P K 
Para meters .................................................................................................2 0
LI S T O F FI G U R E S
Fi g ure 1.
St u d y  Desi g n Sc he maa, b,c ............................................................................7
A P P E N DI C E S
A p pe n di x 1. Cate g orical Classes f or E C G a n d Vit al Si g ns of P ote ntial Cli nical C o ncer n .....2 4
A p pe n di x 2. E xa m ple S A S C o de f or Statistical A nal yses .......................................................2 5
A p pe n di x 3. L ist of A b bre viati o ns...........................................................................................2 6
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 5 of 2 7
1. V E R SI O N HI S T O R Y
T a ble 1 .
S u m m ar y of C h a n ges
Versi o n /
D ate
Ass oci ate d 
Pr ot oc ol 
A m e n d me nt
R ati o n ale
S pecific C h a n ges
1
1 3 J ul 2 0 2 3
Fi nal Pr ot oc ol 
A me n d me nt 1
0 7 J u n 2 0 2 3
N/ A  
N/ A
2
2 1 Mar 2 0 2 4
Fi nal Pr ot oc ol 
A me n d me nt 1
0 7 J u n 2 0 2 3
Pr ot oc ol 
A d mi nistrati ve 
C ha n ge Letter
( P A C L) f or 
A me n d me nt 1
1 4 Dec 2 0 2 3
F o o d effect 
a d de d t o 
S D D 
f or m ulati o n
T hr o u g h o ut: Ge neral u p dates t o a d d 
t he e val uati o n of f o o d effect i n S D D 
f or m ulati o n per P A C L 1 4 -Dec - 2 0 2 3. 
Secti o n 2. 2 : tertiary o bjecti ve of f o o d 
effect u p date d t o matc h P A C L . T y p o
of “ sec o n dar y” c orrecte d . 
Secti o n 3. 2 : fo ot n ote of Ta ble 2
u p date d. 
Secti o n 6. 2 : a nal ysis of f o o d effect i n 
S D D f or m ulati o n a d de d. 
A p pe n di x 3 : a b bre viati o n of P A C L 
a d de d. 
2. I N T R O D U C TI O N
T his st u dy will be t he first ti me t hat P F - 0 7 2 9 3 8 9 3 is a d mi nistere d t o h u m a ns. T he p ur p ose of 
t he st u dy is t o ev al u ate t he s afety, t oler a bility, a n d pl as m a p har mac o ki netic s (P K ) of P F -
0 7 2 9 3 8 9 3 f oll o wi n g a d mi nistr ati o n of esc al ati n g si n gle or al d oses t o he alt hy a d ult 
p artici p a nts.
T his statistical a nal ysis pla n (S A P ) pr o vi des t he detaile d met h o d ol o g y  f or s u m mar y a n d 
statistical a nal yses of t he data c ollecte d i n St u d y C 5 1 7 1 0 0 1 . T his d oc u me nt ma y m o dif y  t he 
pla ns o utli ne d i n t he pr ot oc ol; 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 n or its a nal y sis will als o be reflecte d i n a pr ot oc ol a me n d me nt. 
2. 1. M o dific ati o ns
t o t he A n al ysis Pl a n Descri be d i n t he Pr ot oc ol
N o m o dificati o n. 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 6 of 2 7
2. 2. S t u d y O bjecti ves, E n d p oi nts, a n d Esti m a n ds
T y pe
O bjecti ve
E n d p oi nt
Pri m ary
Pri m ary
Safet y
Secti o n 6. 1

T o ev al u ate t he s afety a n d 
t oler a bility of si n gle asce n di n g 
d oses of P F - 0 7 2 9 3 8 9 3 
a d mi nistere d or ally t o he alt hy 
a d ult p artici p a nts.

Assess me nt of a dverse eve nts, 
cli nic al s afety l a b or at ory tests, 
vit al si g ns, c o nti n u o us c ar di ac
m o nit ori n g, 1 2 -le a d
electr oc ar di o gr a ms, p hysic al 
ex a mi n ati o ns a n d ne ur ol o gic al 
ex a mi n ati o ns.
Sec o n d a ry
Sec o n d ary
P K
Secti o n 6. 2

T o ev al u ate t he P K of P F-
0 7 2 9 3 8 9 3 f oll o wi n g si n gle d oses 
of P F -0 7 2 9 3 8 9 3 a d mi nistere d 
or ally t o he alt hy a d ult 
p artici p a nts.

P K p ar a meters derive d fr o m 
pl as m a P F- 0 7 2 9 3 8 9 3
c o nce ntr ati o ns: C m ax , T m ax , 
A U C l ast, a n d if d at a per mit,
A U C i nf, a n d t½ .
Terti ary/ Ex pl or at ory
Terti ary/ Ex pl or at ory
P K
Secti o n 
6. 3. 1

T o ev al u ate a d diti o n al P K 
p ar a meters of P F -0 7 2 9 3 8 9 3
f oll o wi n g si n gle d oses of P F-
0 7 2 9 3 8 9 3 a d mi nistere d or ally t o 
he alt hy a d ult p artici p a nts.

A d diti o n al P K p ar a meters 
derive d fr o m pl as m a P F -
0 7 2 9 3 8 9 3 c o nce ntr ati o ns: 
C m ax ( d n), A U Cl ast( d n) a n d if d at a 
per mit, A U C i nf( d n), C L/ F a n d 
V z/ F .
P K
Secti o n 
6. 3. 2

T o ev al u ate t he P K of P F-
0 7 2 9 3 8 9 3 f oll o wi n g si n gle
d ose(s) of a cryst alli ne a n d S D D
f or m of P F-0 7 2 9 3 8 9 3 i n f aste d
a n d/ or fe d st ate, if c o n d ucte d.

P K p ar a meters derive d fr o m 
pl as m a P F- 0 7 2 9 3 8 9 3
c o nce ntr ati o ns: C m ax , Tm ax , 
A U C l ast, a n d if d at a per mit,
A U C i nf, a n d t½ .
Bi o mar ker
Secti o n 
6. 3. 3

T o ev al u ate t he effects of si n gle 
asce n di n g d oses of P F -
0 7 2 9 3 8 9 3 o n bi o m arker(s) of 
tr a ns p orter activity, if fe asi ble & 
a n alyze d.

F or e ac h bi o m arker ( as 
a p plic a ble): A U C 2 4 a n d C m ax
T here are n o esti ma n ds f or t his st u d y .
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 7 of 2 7
2. 3. St u d y Desi g n
T his is a r a n d o mize d, i nvesti g at or- a n d p artici p a nt -bli n d, s p o ns or -o pe n, pl ace b o -c o ntr olle d,
first-i n-h u m a n, si n gle asce n di n g or al d ose, 4 -peri o d, cr oss over st u dy of P F - 0 7 2 9 3 8 9 3
a d mi nistere d t o he alt hy a d ult p artici p a nts. A p pr oxi m ately 2 4 he alt hy a d ult p artici p a nts ( u p 
t o 3 c o h orts of a p pr oxi m ately 8 p artici p a nts e ac h) will be e nr olle d i n t his st u dy. T he first 2
c o h orts are pl a n ne d, a n d t he t hir d c o h ort is o pti o n al. I n e ac h peri o d, p artici p a nts will be
r a n d o mize d t o eit her P F- 0 7 2 9 3 8 9 3 or pl ace b o i n a r ati o of 3: 1. E ac h p artici p a nt is pl a n ne d 
t o u n der g o u p t o 4 tre at me nt peri o ds receivi n g u p t o 4 d oses of P F- 0 7 2 9 3 8 9 3 a n d u p t o 2 
d oses of pl ace b o.
Prec a uti o n ary se nti nel d osi n g will be use d i n a ny peri o d ev al u ati n g esc al ati n g d oses of P F -
0 7 2 9 3 8 9 3 a n d m ay be o mitte d f or peri o ds w he n re pe ati n g a d ose level or a d mi nisteri n g a 
l o wer d ose level t h a n previ o usly ev al u ate d. F or peri o ds wit h se nti nel d osi n g, t w o 
p artici p a nts ( 1 receivi n g P F- 0 7 2 9 3 8 9 3 a n d 1 receivi n g pl ace b o) will be d ose d i niti ally
bef ore t he re m ai ni n g p artici p a nts of t h at peri o d are d ose d. S afety a n d t oler a bility d at a
t hr o u g h at le ast 2 4 h o urs p ost- d ose f or t he se nti nel p artici p a nts will be revie we d pri or t o
d osi n g t he re m ai ni n g p artici p a nts of t h at peri o d.
T he st u d y  desi g n sc he ma is s h o w n bel o w i n Fi g ure 1.
Fi g ure 1 .
St u d y Desi g n Sc he m a a, b,c
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 8 of 2 7
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S: D E FI NI TI O N S A N D 
C O N V E N TI O N S
3. 1. Pri m ar y E n d p oi nt(s)
Pri mar y  e n d p oi nts i ncl u de assess me nt of a d verse e ve nts ( A Es), cli nical safet y la b orat or y 
tests, vital si g ns, c o nti n u o us car diac m o nit ori n g, 1 2-lea d electr ocar di o gra ms ( E C G), p hys ical 
e xa mi nati o ns a n d ne ur ol o gical e xa mi nati o ns d uri n g t he e ntire st u d y, b y peri o d .
A n y  e ve nts occ urri n g f oll o wi n g start of st u d y i nter ve nti o n (ie, treat me nt wit h P F- 0 7 2 9 3 8 9 3 
or place b o) will be c o u nte d as treat me nt e mer ge nt. 
E ve nts t hat occ ur i n a n o n -treat me nt peri o d (e g, was h o ut or f oll o w-u p) will be c o u nte d as 
treat me nt e mer ge nt a n d attri b ute d t o t he m ost rece nt treat me nt ta ke n.
A 3 -tier a p pr oac h f or s u m marizi n g a d verse e ve nts will n ot be use d d ue t o t he l o w n u m ber of 
partici pa nts pla n ne d t o be recr uite d. 
T he f oll o wi n g data are c o nsi dere d i n sta n dar d safet y  s u m maries (see pr ot oc ol f or c ollecti o n 
da y s a n d list of para meters):

a d verse e ve nts,

la b orat or y data (e xce pt data fr o m scree ni n g visit),

vital si g ns data,

E C G res ults ,

car diac m o nit ori n g, 

p h y sical e xa mi nati o ns, 

ne ur ol o gical e xa mi nati o ns.
3. 1. 1. A d v erse E ve nts
A n a d verse e ve nt is c o nsi dere d a Treat me nt -E mer ge nt A d verse E ve nt ( T E A E) if t he e ve nt 
starte d d uri n g t he effecti ve d urati o n of treat me nt. All e ve nts t hat start o n or after t he first d ose 
of st u d y i nter ve nti o n, b ut bef ore t he e n d of t he st u d y w ill be fla g ge d as T E A Es. T he al g orit h m 
will n ot c o nsi der a n y e ve nts t hat starte d pri or t o t he first d ose date.
3. 1. 2. Cli nic al S afet y L a b or at or y Tests
Safet y  la b orat or y tests  will be perf or me d as descri be d i n t he pr ot oc ol. 
T he i nvesti g at or m ust revie w t he l a b or at ory re p ort, d oc u me nt t his revie w, a n d rec or d a ny 
cli nic ally si g nific a nt c h a n ges occ urri n g d uri n g t he st u dy i n t he A E secti o n of t he C R F. 
Cli nic ally si g nific a nt a b n or m al l a b or at ory test fi n di n gs are t h ose t h at are n ot ass oci ate d wit h 
t he u n derlyi n g dise ase, u nless j u d ge d by t he i nvesti g at or t o be m ore severe t h a n ex pecte d f or 
t he p artici p a nt’s c o n diti o n.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 9 of 2 7
Baseli ne will be t he last pre -d ose meas ure me nt i n eac h st u d y peri o d. C ha n ge fr o m baseli ne
( C F B) will be calc ulate d f or all p ost -baseli ne ti me p oi nts.
T o de ter mi ne if t here are a n y cli nicall y si g nifica nt la b orat or y a b n or malities, t he 
he mat ol o gical, cli nical c he mistr y  (ser u m) a n d uri nal ysis safety tests will be assesse d a gai nst 
t he criteria s pecifie d i n t he s p o ns or re p orti n g sta n dar ds. T he assess me nt will ta ke i nt o 
acc o u nt w het her eac h partici pa nt’s baseli ne test res ult is wit hi n or o utsi de t he la b orat or y  
refere nce ra n ge f or t he partic ular la b orat or y para meter.
3. 1. 3. Vit al S i g ns
Si n gle s u pi ne bl o o d press ure will be meas ure d at scree ni n g, f oll o w -u p visit a n d earl y 
ter mi nati o n (E T ; if a p plica ble). Tri plicate s u pi ne meas ure me nts will be ta ke n at all ot her 
ti mes as s pecifie d i n t he Sc he d ule of Acti vities ( S o A) of t he pr ot oc ol . T he a vera ge of t he 
tri plicate meas ure me nts will be calc ulate d pri or t o a nalyz i n g t he data. Re s pirat or y rate, p ulse 
rate a n d te m perat ure will be meas ure d at eac h ti me p oi nt s pecifie d i n t he pr ot oc ol.
Baseli ne f or t hese meas ures will be defi ne d as t he last pre- d ose meas ure me nt i n eac h st u d y  
peri o d.
T he f oll o wi n g e n d p oi nts will be deter mi ne d:

C ha n ge f r o m baseli ne i n s yst olic a n d diast olic B P, p ulse rate, te m perat ure, a n d 
res pirat or y rate

T he mi ni m u m a n d ma xi m u m p ost -d ose s y st olic a n d diast olic B P, p ulse rate,
te m perat ure, a n d res pirat or y rate

T he ma xi m u m i ncrease a n d decrease fr o m baseli ne o ver all meas ure me nts ta ke n 
p ost d ose f or sys t olic a n d diast olic B P, p ulse rate, te m perat ure, a n d res pirat or y rate 
val ues
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y selecti n g t he ma xi m u m C F B o ver
t he res pecti ve peri o d, e xce pt i n t he case w here a partici pa nt d oes n ot s h o w a n i ncrease. I n 
s uc h a n i nsta nce, t he mi ni m u m decrease s h o ul d be ta ke n. Si milarl y , t he ma xi m u m decrease 
fr o m baseli ne will be deter mi ne d b y selecti n g t he mi ni m u m val ue of t he C F B . I n cases w here 
a partici pa nt d oes n ot s h o w a decrease, t he mi ni m u m i ncrease s h o ul d be ta ke n.
3. 1. 4. C o nti n u o us C ar di ac M o nit ori n g
C o nti n u o us car diac m o nit ori n g will be perf or me d usi n g tele metr y as o utli ne d i n t he pr ot oc ol. 
All a b n or m al r hyt h ms will be rec or de d a n d revie we d by t he st u dy p hysici a n f or t he prese nce 
of r hyt h ms of p ote nti al cli nic al c o ncer n. T he ti me, d ur ati o n, a n d descri pti o n of t he cli nic ally 
si g nific a nt eve nt will be rec or de d i n t he C R F.
E ve nts dee me d of cli nical c o ncer n will be rec or de d as A Es a n d will be s u m marize d as part of 
t he sta n dar d A E o ut p uts.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 0 of 2 7
3. 1. 5. 1 2 -Le a d E C G
A si n gle 1 2 -lea d E C G will be o btai ne d o n all partici pa nts at scree ni n g, f oll o w-u p visit a n d at 
E T (if a p plica ble). 1 2 -lea d E C Gs will be rec or de d i n tri plicate at all ot her ti mes as s pecifie d
i n t he t he pr ot oc ol. T he a vera ge of t he tri plicate rea di n gs c ollecte d at eac h assess me nt ti me 
will be calc ulate d f or eac h E C G para meter. If o ne or t w o of t he tri plicates are missi n g, t he 
n o n - missi n g val ues will be use d f or t he a vera ge, a n d missi n g values will n ot be i m p ute d.
T he mea n of t he t hree a vera ges of t he tri plic ate E C G me as ure me nts c ollecte d at - 1. 0, - 0. 5, 
a n d 0 h o urs pre - d ose o n D ay 1 of e ac h peri o d will serve as e ac h p artici p a nt’s baseli ne val ue
f or t h at peri o d. If o ne or t w o of t he a vera ges are missi n g, t he n o n - missi n g a vera ges will be 
use d f or t he mea n, a n d missi n g val ues will n ot be i m p ute d.
E C G e n d p oi nts i ncl u de heart rate, Q T i nter val, P R i nter val a n d Q Tc F a n d Q R S c o m ple x. If 
n ot s u p plie d Q Tc F will be deri ve d usi n g Fri dericia’s heart rate c orrecti o n f or m ula:
Q Tc F ( msec) = Q T ( msec) / ( R R)1/ 3, w here R R (sec) = 6 0/ Heart Rate (if R R n ot pr o vi de d).
T he f oll o wi n g e n d p oi nts will be deter mi ne d:

C ha n ge fr o m baseli ne i n Q T, Q Tc F, P R, Q R S i nter val a n d heart rate

T he ma xi m u m p ost -d ose Q Tc F, heart rate, P R a n d Q R S i nter val

T he ma xi m u m i ncrease fr o m baseli ne o ver all meas ure me nts ta ke n p ost -d ose f or 
Q Tc F, heart rate, P R a n d Q R S val ues
T he ma xi m u m i ncrease fr o m baseli ne will be calc ulate d b y selecti n g t he ma xi m u m c ha n ge 
fr o m baseli ne o ver t he res pective peri o d, e xce pt i n t he case w here a partici pa nt d oes n ot 
s h o w a n i ncrease. I n s uc h a n i nsta nce, t he mi ni m u m decrease s h o ul d be ta ke n.
3. 1. 6. P h ysic al E x a mi n ati o ns
C o m plete p h y sical e xa mi nati o ns will be c o n d ucte d at scree ni n g or u p o n a d missi o n f or a 
partici pa nt’ s first peri o d i n t he st u d y. At all ot her ti me p oi nts, a brief p h ysical e xa m ma y be 
perf or me d f or t he fi n di n gs d uri n g a pre vi o us e xa m or ne w/ o pe n A Es at t he i n vesti gat ors 
discreti o n. Hei g ht a n d wei g ht will o nl y  be meas ure d at t he scree ni n g visit.
P hysic al e x a mi n ati o n fi n di n gs c ollecte d d uri n g t he st u dy 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 ysical 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 will be s u m marize d as part of t he sta n dar d 
A E o ut p ut . 
3. 1. 7. Ne ur ol o gic al E x a mi n ati o ns
Ne ur ol o gic al ex a mi n ati o ns m ay be c o n d ucte d by a p hysici a n, tr ai ne d p hysici a n's assist a nt, 
or n urse pr actiti o ner as acce pt a ble acc or di n g t o l oc al re g ul ati o n at t he n o mi n al ti me p oi nts
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 1 of 2 7
s pecifie d i n t he S o A. T he ne ur ol o gic al ex a m will c o nsist of assess me nt of hi g her c ortic al
f u ncti o n, t he cr a ni al nerves, m ot or f u ncti o n, dee p te n d o n reflexes, se ns ory ex a m, a n d
c o or di n ati o n a n d g ait. A d diti o n al ne ur ol o gic al ex a mi n ati o ns t h at are o utsi de of S o A (e g, t o
ev al u ate a n A E) m ay be c o n d ucte d at t he discreti o n of i nvesti g at or. All ne ur ol o gic al ex a ms
s h o ul d be d o ne t o t he exte nt nee de d t o assess t he p artici p a nt f or a ny p ote nti al c h a n ges i n
ne ur ol o gic al st at us, as deter mi ne d by t he i nvesti g at or ( or desi g nee). C h a n ges i n t he ti mi n g 
or a d diti o n of ti me p oi nts f or t he ne ur ol o gic al ex a mi n ati o ns m ay occ ur b ase d o n e mer gi n g 
d at a.
A n y  u nt o war d fi n di n gs i de ntifie d o n ne ur ol o gical e xa mi nati o ns, c o n d ucte d d uri n g t he acti ve 
c ollecti o n peri o d will be ca pt ure d as A Es or S A Es , if t h ose fi n di n gs meet t he defi niti o n of a n 
A E or S A E, a n d will be s u m marize d as part of t he sta n dar d A E o ut p uts .
3. 2. Sec o n d ar y E n d p oi nt(s)
Bl o o d sa m ples f or P K a nal y sis of P F - 0 7 2 9 3 8 9 3 will be ta ke n acc or di n g t o t he S o A i n t he 
pr ot oc ol. T he pl as m a P K p ar a meters f or P F- 0 7 2 9 3 8 9 3, f oll o wi n g or al d ose a d mi nistr ati o n, 
will be derive d fr o m t he pl as m a c o nce ntr ati o n -ti me pr ofiles usi n g st a n d ar d 
n o nc o m p art me nt al met h o ds as det aile d i n Ta ble 2, as d at a per mit . Ta ble 2 als o s h o ws t he 
a nal ys is scale a n d met h o d f or eac h para meter. 
I n all cases, a ct u al P K s a m pli n g ti mes will be use d i n t he deriv ati o n of P K p ar a meters. If 
act u al P K s a m pli n g ti mes are n ot av ail a ble, n o mi n al P K s a m pli n g ti mes will be use d i n t he 
deriv ati o n of P K p ar a meters.
T he f oll o wi n g plas ma P K para meters as descri be d i n Ta ble 2 will be deter mi ne d. 
T a ble 2.
Pl as m a P F - 0 7 2 9 3 8 9 3 P K P ar a meters
P ar a me ter
Defi niti o n
Met h o d of Deter mi n ati o n
A n al ysis 
Sc ale
P F -
0 7 2 9 3 8 9
3
A U C l ast
Are a u n der t he 
pl as m a
c o nce ntr ati o n-ti me 
pr ofile fr o m
ti me 0 t o t he ti me of 
t he l ast
q u a ntifi a ble 
c o nce ntr ati o n ( C l ast)
Li ne ar/ L o g tr a pez oi d al 
met h o d
l n
D, A
A U C i nf*
Are a u n der t he
pl as m a
c o nce ntr ati o n-ti me 
pr ofile fr o m
ti me 0 extr a p ol ate d 
t o i nfi nite ti me
A U C l ast + ( C l ast*/kel), 
w here C l ast* is t he 
pre dicte d pl as m a 
c o nce ntr ati o n at t he l ast 
q u a ntifi a ble ti me p oi nt 
esti m ate d fr o m t he l o g-
li ne ar re gressi o n a n alysis
l n
D, A
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 2 of 2 7
C m ax
M axi m u m pl as m a 
c o nce ntr ati o n
O bserve d directly fr o m 
d at a
l n
D, A
T m ax
Ti me f or C m ax
O bserve d directly fr o m 
d at a as ti me of first 
occ urre nce
R  
D
t½ *
Ter mi n al eli mi n ati o n 
h alf -life
L o g e( 2)/kel, w here kel is 
t he ter mi n al p h ase r ate 
c o nst a nt c alc ul ate d by a 
li ne ar re gressi o n of t he 
l o g-li ne ar c o nce ntr ati o n-
ti me c urve. O nly t h ose 
d at a p oi nts j u d ge d t o 
descri be t he ter mi n al l o g -
li ne ar decli ne will be use d 
i n t he re gressi o n.
R  
D
K e y : l n = nat ural-l o g tra nsf or me d, R =ra w ( u ntra nsf or me d),
D = dis pla y e d wit h descri pti ve statistics,
A =a nal ys e d usi n g a statistical m o del (f or e val uati n g f o o d effect)
* =if data per mit
T last will als o be pr o vi de d as a s u p p ort para meter f or A U C last. Tlast val ues will o nl y  be liste d
a n d n ot s u m marize d.
3. 3. Ot her E n d p oi nt(s)
3. 3. 1. A d diti o n al Pl as m a P F -0 7 2 9 3 8 9 3 P a r a meters
A d diti o nal plas ma P F - 0 7 2 9 6 8 9 3 P K para meters, as descri be d i n Ta ble 3 , will be deter mi ne d. 
T a ble 3 .
A d diti o n al P F -0 7 2 9 3 8 9 3 P K P ar a meters
P ar a meter
Defi niti o n
Met h o d of Deter mi n ati o n
A n al ysis 
Sc ale
P F -
0 7 2 9 3 8 9
3
C L/ F *
A p p are nt cle ar a nce
D ose/ A U C i nf
l n
D
Vz/ F *
A p p are nt v ol u me of 
distri b uti o n
D ose/( A U C i nf× kel)
l n
D
A U C l ast( d n)
D ose - n or m alize d 
A U C l ast
A U C l ast/ D ose
l n
D
A U C i nf( d n) *
D ose - n or m alize d 
A U C i nf
A U C i nf/ D ose
l n
D
C m ax ( d n)
D ose - n or m alize d 
C m ax
C m ax / D ose
l n
D
K e y : l n = nat ural-l o g tra nsf or me d,
D = dis pla y e d wit h descri pti ve statistics,
* =if data per mit
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 3 of 2 7
3. 3. 2. P l as m a P F- 0 7 2 9 3 8 9 3 P K p ar a meters d uri n g cr yst alli ne f or m peri o d if c o n d ucte d
T he plas ma P F -0 7 2 9 6 8 9 3 P K para meters descri be d i n Ta ble 2 a n d d ose n or malize d P K 
para meters (if re q uire d) i n Ta ble 3 will als o be deter mi ne d after c r ystalli ne P F -0 7 2 9 3 8 9 3 oral 
s us pe nsi o n a d mi nistrati o n. 
3. 3. 3. Tr a ns p orter bi o m ar kers ( o pti o n al)
T ra ns p orter bi o mar kers (e g, 
) will be a nal yze d if feasi ble a n d dee me d necessar y.
T he A U C 2 4 a n d C ma x of eac h tra ns p orter bi o mar ker will be deri ve d if a p plica ble, w here the 
a nal ys is scale is l n. 
3. 4. B aseli ne V ari a bles
N ot a p plica ble. 
3. 5. S afet y E n d p oi nts
See Secti o n 3. 1 f or details.
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S )
D ata f or all partici pa nts will be assesse d t o deter mi ne if partici pa nts meet t he criteria f or 
i ncl usi o n i n eac h a nalys is p o p ulati o n pri or t o u n bli n di n g a n d releasi n g t he data base a n d 
classificati o ns will be d oc u me nte d per sta n dar d o perati n g pr oce d ures.
P artici p a nt 
A n alysis Set
Descri pti o n
A p plic a ble 
A n al ysis (f or 
a d diti o nal 
i nf or mati o n  refer t o
secti o n 6 )
E nr olle d 
“ E nr olle d ” me a ns a p artici p a nt’s, a gree me nt t o 
p artici p ate i n a cli nic al st u dy 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
r a n d o miz ati o n t o st u dy i nterve 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 ny st u d y 
acti vit y after scree ni n g. P ote ntial partici pa nts w h o 
are scree ne d f or t he p ur p ose of deter mi ni n g 
eli gi bilit y f or t he st u d y, b ut d o n ot partici pate i n 
t he st u d y, are n ot c o nsi dere d e nr olle d, u nless 
ot her wise s pecifie d b y t he pr ot oc ol.
S afety 
a n alysis set
All p artici p a nts r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o t ake at le ast 1 d ose of st u dy 
i nterve nti o n. P artici p a nts will be a n alyze d 
acc or di n g t o t he st u dy i nterve nti o n t hey act u ally 
receive d.
S ecti o n 6. 1 S afet y 
e n d p oi nts 
s u m maries a n d 
a nla yses
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 4 of 2 7
P artici p a nt 
A n alysis Set
Descri pti o n
A p plic a ble 
A n al ysis (f or 
a d diti o nal 
i nf or mati o n  refer t o
secti o n 6 )
P K 
C o nce ntr ati o n 
Set
All p artici p a nts r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o receive at le ast 1 d ose of 
st u dy i nterve nti o n a n d i n w h o m at le ast 1 pl as m a 
c o nce ntr ati o n v al ue is re p orte d.
Secti o n 6. 2 , Secti o n
6. 3. 1 , Secti o n 6. 3. 2
P K e n d p oi nts
P K 
P ar a meter Set
All p artici p a nts r a n d o mly assi g ne d t o st u dy 
i nterve nti o n a n d w h o receive at le ast 1 d ose of 
st u dy i nterve nti o n a n d h ave at le ast 1 of t he P K 
p ar a meters of i nterest c alc ul ate d.
Secti o n 6. 2 , Secti o n
6. 3. 1 , Secti o n 6. 3. 2
P K e n d p oi nts
Bi o mar ker 
C o nce ntrati o n 
Set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y 
i nter ve nti o n a n d w h o recei ve at least 1 d ose of 
st u d y i nter ve nti o n a n d i n w h o m at least 1 plas ma 
bi o mar ker c o nce ntrati o n val ue is re p orte d.
Secti o n 6. 3. 3
Bi o mar ker e n d p oi nts
Bi o mar ker 
Para meter Set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y 
i nter ve nti o n a n d w h o recei ve at least 1 d ose of 
st u d y i nter ve nti o n a n d ha ve at least 1 of t he 
Bi o mar ker para meters of i nterest calc u late d.
Secti o n 6. 3. 3
Bi o mar ker e n d p oi nts
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S
5. 1. H y p ot heses a n d Decisi o n R ules
T here is n o statistical h y p ot hesis testi n g pla n ne d f or t his st u d y, a n d n o statistical decisi o n 
r ules will be a p plie d.
5. 2. Ge ner al Met h o ds
U nless ot her wise state d, all s u m maries a n d pl ots will be prese nte d b y d ose a n d treat me nt. 
Eac h f or m ulati o n of P F- 0 7 2 9 3 8 9 3 a d mi nistere d d uri n g t he st u d y a n d fasti n g stat us will b e 
c o nsi dere d as se parate treat me nts. If a d ose le vel is re peate d acr oss 2 or m ore c o h orts, t he 
data will be c o m bi ne d, u nless t he d ose is i n a differe nt f or m ulati o n or f o o d state, i n w hic h 
case t he d ose w o ul d be re p orte d se paratel y.
U nless ot her wise state d, t he s u m mar y ta bles a n d/ or statistical a nal ys es will o nl y  incl u de a 
si n gle p o ole d place b o gr o u p acr oss all i ncl u de d c o h orts wit h S D D f or m ulati o n. Place b o will 
be p o ole d fr o m all d ose escalati o n peri o ds b ut n ot f or t he fe d peri o d (if c o n d ucte d) n or f or 
c yrstalli ne f or m ulati o n peri o d (if c o n d ucte d).
5. 2. 1. A n al yses f or C o nti n u o us E n d p oi nts
U nless ot her wise state d, c o nti n u o us varia bles will be prese nte d usi n g s u m mar y  statistics: 
n u m ber of o bser vati o ns, arit h metic mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d 
ma xi m u m val ues. 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 5 of 2 7
G e o metric mea n a n d ge o metric c v % will als o be prese nte d f or c o nti n o us varia bles usi n g l n 
a nal ys is scale.
5. 2. 2. A n al yses f or C ate g oric al E n d p oi nts
Cate g orical varia bles will be prese nte d usi n g s u m mar y  statistics: n u m ber of o bser vati o ns a n d 
perce nta ges.
5. 2. 3.
M i xe d Effect M o del
A mi xe d effects m o del wit h treat me nt as a fi xe d effect a n d partici pa nt as a ra n d o m effect will 
be use d f or t he a nal ys is of f o o d effect o n P F -0 7 2 9 6 8 9 3 P K e n d p oi nts. 
Esti mates of t he a dj uste d (least s q uares) mea n differe nces ( Test-refere nce) a n d c orres p o n di n g 
9 0 % c o nfi de nce i nter vals ( CIs) will be o btai ne d fr o m t he m o del. T he a dj uste d mea n 
differe nces a n d 9 0 % CI s 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 s f or t he rati os.
T he mi xe d effects m o del will be i m ple me nte d usi n g S A S Pr oc Mi xe d, wit h R E M L  
esti mati o n met h o d a n d t he Ke n war d -R o ger de grees of free d o m al g orit h m .
Resi d uals fr o m t he m o dels will be e xa mi ne d f or n or malit y  a n d t he prese nce of o utliers via 
vis ual i ns pecti o n of pl ots of resi d uals vs pre dicte d val ues a n d n or mal pr o ba bilit y  pl ots of 
resi d uals, b ut t hese will n ot be i ncl u de d i n t he cli nical st u d y re p ort. If t here are maj or 
de viati o ns fr o m n or malit y or o utliers ( w here st u de ntize d [c o n diti o nal] resi d uals are greater 
t ha n 3 or less t ha n -3), t he n t he effect of t hese o n t he c o ncl usi o ns ma y  be i n vesti gate d 
t hr o u g h alter nati ve tra nsf or mati o ns a n d/ or a nalys es e xcl u di n g o utliers. J ustificati o n f or a n y 
alter nati ve t o t he pla n ne d a nal ys is will be gi ve n i n t he re p ort of t he st u d y if a p plica ble.
E xa m ple S A S c o de is pr o vi de d i n A p pe n di x 2 .
5. 3.
Met h o ds t o M a n a ge Missi n g D at a
5. 3. 1. Missi n g S afet y D at a
F or t he a nal ysis of safet y e n d p oi nts, t he s p o ns or data sta n dar d r ules f or i m p utati o n will be 
a p plie d.
5. 3. 2. Missi n g P K C o nce ntr ati o n D at a
I n all P K data prese ntati o ns (e xce pt listi n gs), c o nce ntrati o ns bel o w t he li mit of q ua ntificati o n 
( B L Q) will be set t o zer o. In listi n gs, B L Q val ues will be re p orte d as “ < L L O Q”, w here 
L L O Q  will be re place d wit h t he val ue f or t he l o wer li mit of q ua ntificati o n ( L L O Q).
I n P K s u m mar y  ta bles a n d pl ots of mea n/ me dia n pr ofiles, statistics will be calc ulate d ha vi n g 
set c o nce ntrati o ns t o missi n g if o ne of t he f oll o wi n g cases is tr ue:
1.
A c o nce ntrati o n has bee n c ollecte d as N D (ie n ot d o ne) or N S (ie n o sa m ple),
2.
A de viati o n i n sa m pli n g ti me is of s ufficie nt c o ncer n or a c o nce ntrati o n has bee n
fla g ge d a n o mal o us by t he p har mac o ki neticist/statisticia n.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 6 of 2 7
N ot e t hat s u m mar y statistics will n ot be prese nte d at a partic ular ti me p oi nt if m ore t ha n 5 0 %
of t he data are missi n g.
Partici pa nts w h o e x perie nce e ve nts t hat ma y  affect t heir P K pr ofile (e. g., lac k of c o m plia nce 
wit h d osi n g or v o miti n g) ma y  be e xcl u de d fr o m t he P K a nalys is. At t he discreti o n of t he 
p har mac o ki neticist, a c o nce ntrati o n val ue ma y  als o be e xcl u de d if t he de viati o n i n sa m pli n g 
ti me is of s ufficie nt c o ncer n or if t he c o nce ntrati o n is a n o mal o us f or a ny ot her reas o n.
A f ull list of pr ot oc ol de viati o ns will be c o m pile d a n d re vie we d t o i de ntif y  maj or a n d mi n or 
de viati o ns pri or t o data base cl os ure.
5. 3. 3. Missi n g Pl as m a P K P ar a meters
Act ual P K sa m pli n g ti mes will be use d i n t he deri vati o n of plas ma P K para meters.
If a P K para meter ca n n ot be deri ve d fr o m a partici pa nt’s c o nce ntrati o n data, t he para meter 
will be c o de d as N C (ie n ot calc ulate d). ( N ote t hat N C val ues will n ot be ge nerate d be y o n d 
t he da y t hat a partici pa nt disc o nti n ues). 
I n s u m mar y ta bles, statistics will be calc ulate d by setti n g N C val ues t o miss i n g; a n d statistics 
will be prese nte d f or a partic ular d ose wit h ≥ 3 e val ua ble meas ure me nts. F or statistical 
a nal ys es (i.e. mi xe d effects m o del), P K para meters c o de d as N C will als o be set t o missi n g; 
a n d a nal ys es will n ot be perf or me d f or a partic ular par a meter if m ore t ha n 5 0 % of t he data 
are N C.
If a n i n di vi d ual partici pa nt has a k n o w n biase d esti mate of a P K para meter ( d ue f or e xa m ple
t o a n u ne x pecte d e ve nt s uc h as v o miti n g bef ore all t he c o m p o u n d is a de q uatel y a bs or be d i n
t he b o d y), t his will be f o ot n ote d i n s u m mar y ta bles a n d m a y  n ot be i ncl u de d i n t he 
calc ulati o n of s u m mar y  statistics or statistical a nal yses.
6. A N A L Y S E S A N D S U M M A RI E S
6. 1. Pri m ar y E n d p oi nt (s)
F or all prese ntati o ns, st u d y  da y will refer t o t he da y wit hi n a partic ular treat me nt peri o d, 
u nless ot her wise s pecifie d.
6. 1. 1. A d verse E ve nts
A d verse e ve nts will be liste d a n d s u m marize d b y  d ose a n d treat me nt (if a p plica ble) a n d 
o verall, i n acc or da nce wit h s p o ns or re p orti n g sta n dar ds usi n g t he safet y  a nal ysis set defi ne d 
i n Secti o n 4 . 
T he A Es will be prese nte d s orte d i n desce n di n g fre q ue nc y  base d o n t he o verall n u m ber of 
A Es ( b y preferre d ter m or s yste m or der class as a p pr o priate) acr oss treat me nts .
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 7 of 2 7
6. 1. 2. Cli nic al S afet y L a b or at or y Tests 
Safet y  la b orat or y data will be liste d a n d s u m marize d b y d ose a n d treat me nt (if a p plica ble)
a n d o verall, i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds usi n g t he safet y a nalys is set 
defi ne d i n Secti o n 4 . Baseli ne is as defi ne d i n Secti o n 3. 1. 2 .
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, 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.
I n s u m mar y a n d listi n g ta bles, la b orat or y a b n or malities occ urri n g pre-d ose o n Da y  - 1 f or 
eac h peri o d starti n g wit h Peri o d 2 , will be attri b ute d t o t he treat me nt fr o m t he pre vi o us 
peri o d ( e g, f or C o h ort 1, a n occ urre nce pre -d ose at Peri o d 2 Da y  -1 will be attri b ute d t o t he 
Peri o d 1 d ose) .
6. 1. 3. Vit al Si g ns
A bs ol ute val ues a n d C F B i n s u pi ne sys t olic a n d diast olic B P , p ulse rate, te m perat ure a n d 
res pirat or y rate will be liste d a n d s u m marize d b y d ose a n d treat me nt a n d ti me p oi nt, 
acc or di n g t o s p o ns or re p orti n g sta n dar ds, usi n g t he safet y a nal ys is set defi ne d i n Secti o n 4 . 
Baseli ne is as defi ne d i n Secti o n 3. 1. 3 .
Mea n a bsol ute val ues a n d C F B f or s u pi ne sys t olic a n d diast olic B P , p ulse rate, te m perat ure,
a n d res pirat or y rate will be pl otte d a gai nst ti me p oi nt . O n eac h pl ot t here will be o ne li ne f or
eac h treat me nt wit h all treat me nts o n t he sa me pl ot . C orres p o n di n g i n di vi d ual pl ots of 
c ha n ges fr o m baseli ne will als o be pr o d uce d f or eac h treat me nt.
Ma xi m u m i ncrease a n d decrease fr o m baseli ne o ver all meas ure me nts ta ke n p ost- d ose f or
s u pi ne s yst olic a n d diast olic B Ps , p ulse rate, te m perat ure a n d res pirat or y rate will be 
s u m marize d b y  treat me nt, acc or di n g t o s p o ns or re p orti n g sta n dar ds.
Mi ni m u m a n d/ or ma xi m u m a bs ol ute val ues a n d C F B f or s u pi ne vital si g ns will als o be 
s u m marize d descri pti vel y by treat me nt usi n g cate g ories as defi ne d i n A p pe n di x 1 . N u m bers 
a n d perce nta ges of parti ci pa nts meeti n g t he cate g orical criteria will be pr o vi de d. All pla n ne d 
a n d u n pla n ne d p ost - d ose ti me p oi nts will be c o u nte d i n t hese cate g orical s u m maries. All 
val ues meeti n g t he criteria of p ote ntial cli nical c o ncer n will be liste d .
Val ues meeti n g t he cat e g orical criteria occ urri n g pre -d ose o n Da y  1 f or eac h peri o d starti n g 
wit h Peri o d 2 , will be attri b ute d t o t he treat me nt fr o m t he pre vi o us peri o d (e. g., f or C o h ort 1, 
a n occ urre nce pre -d ose at Peri o d 2 Da y  1 will be attri b ute d t o t he Peri o d 1 d ose).
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, 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.
6. 1. 4. C o nti n u o us C ar di ac M o nit ori n g
Data will be re vie we d a n d s u m marize d o n a n o n g oi n g basis d uri n g t he st u d y  t o e val uate t he 
safety of partici pa nts. 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 8 of 2 7
All a b n or mal r h yt h ms will be rec or de d a n d re vie we d b y  t he i n vesti gat or f or t he prese nce of 
r h yt h ms of p ote ntial cli nical c o ncer n.  T he ti me, d urati o n, a n d descri pti o n of t he cli nicall y 
si g nifica nt e ve nt will be rec or de d i n t he C R F. E ve nts dee me d of cli nical c o ncer n will be 
rec or de d as A Es a n d will be s u m marize d as part of t he sta n dar d A E o ut p uts.
6. 1. 5. 1 2 -Le a d E C G
A bs ol ute val ues a n d C F B i n Q T, heart rate, Q Tc F, P R a n d Q R S will be s u m marize d b y d ose 
a n d treat me nt a n d ti me p oi nt usi n g s p o ns or re p orti n g sta n dar ds, usi n g t he safety a nal ysis set 
defi ne d i n Secti o n 4 . Baseli ne is as defi ne d i n Secti o n 3. 1. 5 .
Mea n C F B i n Q T, heart rate a n d Q Tc F will be pl otte d a gai nst ti me p ost-d ose. O n eac h pl ot 
t here will be o ne li ne f or eac h treat me nt. C orres p o n di n g i n di vi d ual pl ots of C F B will als o be 
pr o d uce d f or eac h treat me nt.
C ha n ges fr o m baseli ne i n Q Tc F will als o be pl otte d se paratel y  a gai nst dr u g c o nce ntrati o ns of 
P F - 0 7 2 9 3 8 9 3. T his will be a scatter pl ot f or all o bser vati o ns w here Q TcF a n d dr u g
c o nce ntrati o n are rec or de d. Place b o data will als o be i ncl u de d ( wit h dr u g c o nce ntrati o n set t o
zer o). Differe nt s y m b ols will be use d f or eac h treat me nt.
Ma xi m u m i ncrease fr o m baseli ne f or Q Tc F, heart rate, P R a n d Q R S val ues will be 
s u m marize d b y d ose a n d treat me nt, acc or di n g t o s p o ns or re p orti n g sta n dar ds.
E C G e n d p oi nts a n d C F B ( Q Tc F, P R a n d Q R S) will als o be s u m marize d descri pti vel y  b y 
d ose a n d treat me nt usi n g cate g ories as defi ne d i n A p pe n di x 1 . N u m bers a n d perce nta ges of 
partici pa nts meeti n g t he cate g orical criteria will be pr o vi de d. All pla n ne d a n d u n pla n ne d 
p ost d ose ti me p oi nts will be c o u nte d i n t hese cate g orical s u m maries.
Val ues meeti n g t he cate g orical criteria occ urri n g pre -d ose o n Da y  1 f or eac h peri o d starti n g 
wit h Peri o d 2 , will be attri b ute d t o t he treat me nt fr o m t he pre vi o us peri o d (e. g., f or c o h ort 1, 
a n occ urre nce pre -d ose at Peri o d 2 Da y  1 will be attri b ute d t o t he Peri o d 1 d ose).
Listi n gs of partici pa nts wit h a n y si n gle p ost -d ose val ue > 5 0 0 msec will als o be pr o d uce d f or 
Q Tc F.
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, 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.
6. 1. 6. P h ysic al E x a mi n ati o ns
P hysic al ex a mi n ati o n fi n di n gs c ollecte d d uri n g t he st u dy 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 ny u nt o w ar d p hysic al 
ex a mi n ati o n fi n di n gs t h at are i de ntifie d d uri n g t he active 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 will be rec or de d as A Es or S A Es a n d will be s u m marize d as part 
of t he sta n dar d A E o ut p uts.
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, 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.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 9 of 2 7
6. 1. 7. Ne ur ol o gic al E x a mi n ati o ns
Ne ur ol o gical e xa mi nati o n data 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. A n y  u nt o war d 
n e ur ol o gical 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 will be rec or de d as A Es or S A Es a n d will be 
s u m marize d as part of t he sta n dar d A E o ut p uts.
6. 2. Sec o n d ar y E n d p oi nt(s)
T he P K para meters detaile d i n Secti o n 3. 2 will be liste d a n d s u m marize d f or partici pa nts i n
t he P K Para meter A nalys is Set (as defi ne d i n Secti o n 4 ). Missi n g val ues will be ha n dle d as
detaile d i n Secti o n 5. 3. 2 a n d 5. 3. 3 . Eac h P K para meter will be s u m marize d b y d ose (a n d 
f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) as a p plica ble. Eac h s u m mar y will i ncl u de 
t he set of s u m mar y statistics as s pecifie d i n Ta ble 4 .
T a ble 4.
S u m m ar y St atistics f or P F -0 7 2 9 3 8 9 3 Pl as m a P K P ar a meters 
P ar a meter
S u m m ar y St atistics
A U C last, A U Ci nf* , Cma x , 
N, arit h metic mea n, me dia n, c v %, sta n dar d 
de vi ati o n, mi ni m u m, ma xi m u m, ge o metric mea n 
a n d ge o metric c v %.
T ma x
N, me dia n, mi ni m u m, ma xi m u m
t1/ 2*
N, arit h metic mea n, me dia n, c v %, sta n dar d 
de viati o n, mi ni m u m, ma xi m u m.
*I f data per mit
S u p p orti n g data fr o m t he esti mati o n of t ½ will be liste d b y  treat me nt a n d d ose w here 
a p plica ble: ter mi nal p hase rate c o nsta nt ( kel); g o o d ness of fit statistic fr o m t he l o g-li near 
re gressi o n (r2); t he perce nt of A U Ci nf base d o n e xtra p olati o n ( A U C e xtra p %); a n d t he first, last, 
a n d n u m ber of ti me p oi nts use d i n t he esti mati o n of kel. T hese data ma y be i ncl u de d i n t he 
C S R.
P F - 0 72 9 3 8 9 3 c o nce ntrati o ns will be prese nte d usi n g partici pa nts i n t he P K C o nce ntrati o n Set 
(as defi ne d i n Secti o n 4 ) a n d will i ncl u de:

a listi n g of all c o nce ntrati o ns s orte d b y  partici pa nt I D, d ose a n d treat me nt (if 
a p plica ble) a n d n o mi nal ti me p ost - d ose. T he c o nce ntrati o n listi n g will als o i ncl u de 
t he act ual ti mes. De viati o ns fr o m t he n o mi nal ti me will be gi ve n i n a se parate listi n g.

a s u m mar y of c o nce ntrati o ns b y d ose a n d treat me nt (if a p plica ble) a n d n o mi nal ti me 
p ost - d ose, w here t he set of statistics will i ncl u de n, mea n, me dia n, sta n dar d de viati o n, 
c oefficie nt of variati o n (c v), mi ni m u m, ma xi m u m a n d t he n u m ber of c o nce ntrati o ns 
a b o ve t he l o wer li mit of q ua ntificati o n.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 0 of 2 7

i n di vi d ual c o nce ntrati o n-ti me pl ots b y d ose ( o n b ot h li near a n d se mi-l o g scales) a n d 
treat me nt (if a p plica ble) a gai nst act ual ti me p ost - d ose (t here will be se parate s pa g hetti 
pl ots f or eac h d ose a n d treat me nt [if a p plica ble] per scale).

i n di vi d ual c o nce ntrati o n-ti me pl ots b y partici pa nt ( o n b ot h li near a n d se mi-l o g scales) 
a gai nst act ual ti me p ost - d ose (t here will be se parate s pa g hetti pl ots f or eac h d ose a n d 
treat me nt [if a p plica ble] per scale).

me dia n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal 
ti me p ost-d ose b y  d ose (all d oses o n t he sa me pl ot per scale, base d o n t he s u m mar y of 
co nce ntrati o ns b y d ose a n d ti me p ost -d ose) a n d treat me nt (if a p plica ble ).

mea n c o nce ntrati o n -ti me pl ots ( o n b ot h li near a n d se mi-l o g scales) a gai nst n o mi nal 
ti me p ost-d ose b y  d ose (all d oses o n t he sa me pl ot per scale, base d o n t he s u m mar y of 
c o nce ntrati o ns b y  d ose a n d ti me p ost-d ose) a n d treat me nt (if a p plica ble ).
T he scale use d f or t he x - a xis (ti me) of t hese pl ots will be deci de d o n re vie w of t he data, a n d 
will de pe n d o n h o w l o n g P F- 0 7 2 9 3 8 9 3 c o nce ntrati o n is q ua ntifia ble i n t he matri x.
F or s u m mar y  statistics, me dia n a n d mea n pl ots b y sa m pli n g ti me, t he n o mi nal P K sa m pli n g 
ti me will be use d. F or i n di vi d ual partici pa nt pl ots b y ti me, t he act ual P K sa m pli n g ti me will 
be use d.
T o assess a n y f o o d effect i n S D D f or m ulati o n as a tertiar y o bjecti ve, a mi xe d effects m o del
will be perf or me d se paratel y o n t he nat ural l o g tra nsf or me d A U Ci nf, A U Clast, a n d Cma x wit h 
fasti n g c o n diti o n i ncl u de d as a fi xe d effect a n d partici pa nt as a ra n d o m effect as descri be d i n 
Secti o n 5. 2. 3 . O nl y  data fr o m t he res pecti ve peri o ds i n t he c o h ort 3 will be i ncl u de d. T he 
faste d state will be t he refere nce a n d t he fe d state will be t he test treat me nt.
6. 3. Ot her E n d p oi nts
6. 3. 1. A d diti o n al P l as m a P F -0 7 2 9 3 8 9 3 P a r a meters
A d diti o nal P K para meters detaile d i n Secti o n 3. 3. 1 will be liste d a n d s u m marize d f or 
partici pa nts i n t he P K Para meter A nalys is Set (as defi ne d i n Secti o n 4 ). Missi n g val ues will 
be ha n dle d as detaile d i n Secti o n 5. 3. 2 a n d 5. 3. 3 . Eac h P K para meter will be s u m marize d b y 
d ose (a n d f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) as a p plica ble. Eac h s u m mar y will 
i ncl u de t he set of s u m mar y statistics as s pecifie d i n Ta ble 5.
T a ble 5.
S u m m ar y St atistics f or A d diti o n al P F -0 7 2 9 3 8 9 3 Pl as m a P K P ar a meters
P ar a meter
S u m m ar y St atistics
C L / F* , Vz/ F* , A U Clast( d n), A U Ci nf
( d n)* , Cma x ( d n)
N, arit h metic mea n, me dia n, c v %, sta n dar d 
de viati o n, mi ni m u m, ma xi m u m, ge o metric mea n 
a n d ge o metric c v %.
*I f data per mit
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 1 of 2 7
B o x a n d w his ker pl ots f or d ose -n or malize d P K para meters [ A U C i nf ( d n), AU C last ( d n) a n d 
C ma x ( d n)] will be prese nte d i n l o garit h mic scale b y d ose a n d treat me nt (if a p plica ble) a n d 
o verlai d wit h o bser ve d val ues of i n di vi d ual partici pa nts a n d ge o metric mea ns. Ge o metric 
mea ns will ha ve a differe nt s y m b ol t ha n t he i n di vi d ual val ues. I n di vi d ual val ues fr o m 
differe nt c o h orts will als o ha ve a differe nt s y m b ol. A f o ot n ote will be a d de d t o t he pl ots t o 
i n dicate t hat ge o metric mea ns are prese nte d a n d t hat data fr o m all c o h orts are prese nte d o n 
t he pl ot.
T he n o mi nal P K sa m pli n g ti me will be use d f or s u m mar y  statistics a n d rele va nt pl ots.
6. 3. 2. Pl as m a P F - 0 7 2 9 3 8 9 3 P K p ar a meters d uri n g cr yst alli ne f or m peri o d if c o n d ucte d
If t he f or m ulati o n a n d/ or f o o d effects are assesse d, t he P K para meters descri be d i n Secti o n 
3. 3. 2 will als o be s u m marize d descri pti vel y  as descri be d a b o ve i n Secti o n 6. 2 b y  f or m ulati o n 
a n d/ or fasti n g c o n diti o n.
T o assess a n y f o o d effect i n cr ystalli ne f or m ulati o n, a mi xe d effects m o del will be perf or me d 
se p ar ately o n t he n at ur al l o g tr a nsf or me d A U C i nf, A U Cl ast, a n d Cm ax ( d ose-n or m alize d pri or
t o a n alysis, if a p pr o pri ate) wit h fasti n g c o n diti o n i ncl u de d as a fixe d effect a n d p artici p a nt 
as a r a n d o m effect as descri be d i n Secti o n 5. 2. 3 . If perf or me d, o nl y data fr o m t he res pecti ve 
peri o ds t hat i ncl u des t he cr ys talli ne f or m ulati o n will be i ncl u de d. T he faste d state will be t he 
refere nce a n d t he fe d state will be t he test treat me nt.
6. 3. 3. Tr a ns p ort er bi o m ar kers ( o pti o n al)
If a nal yz e d, the A U C 2 4 a n d C ma x of tra ns p orter bi o mar kers (e g, 
) will be liste d a n d 
s um marize d f or partici pa nts i n t he Bi o mar ker Para meter A nal ys is Set (as defi ne d i n Secti o n
4 ). Missi n g val ues will be ha n dle d as detaile d i n Secti o n 5. 3. 2 . Eac h bi o mar ker para meter 
will be s u m marize d b y  d ose (a n d f or m ulati o n a n d fasti n g c o n diti o n, if a p pr o priate) as 
a p plica ble. Eac h s u m mar y will i ncl u de N, arit h metic mea n, me dia n, c v %, sta n dar d de viati o n,
mi ni m u m, ma xi m u m, ge o metric mea n a n d g e o metric c v %.
If a nal yz e d, bi o mar ker c o nce ntrati o ns will be prese nte d usi n g partici pa nts i n t he Bi o mar ker 
C o nce ntrati o n Set (as defi ne d i n Secti o n 4 ) a n d will i ncl u de listi n g, s u m mar y statistics, a n d 
pl ots si milarl y descri be d i n Secti o n 6. 2 . 
T he scale use d f or t he x - a xis (ti me) of t hese pl ots will be deci de d o n re vie w of t he data, a n d 
will de pe n d o n h o w l o n g bi o mar ker c o nce ntrati o n is q ua ntifia ble i n t he matri x.
F or s u m mar y  statistics, me dia n a n d mea n pl ots b y sa m pli n g ti me, t he n o mi nal bi o mar ker 
sa m pli n g ti me will be use d. F or i n di vi d ual partici pa nt pl ots b y ti me, t he act ual bi o mar ker 
sa m pli n g ti me will be use d.
6. 4. S u bset A n al yses
N o s u bset a nal ys es will be perf or me d. 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)
C CI


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 2 of 2 7
6. 5. B aseli ne a n d Ot her S u m m aries a n d A n al yses
6. 5. 1. B aseli ne S u m m aries
De m o gra p hic data (a ge, bi ol o gical se x, race, et h nicit y , wei g ht, b o dy mass i n de x a n d hei g ht)
will be s u m mari ze d acr oss all partici pa nts i n t he safet y p o p ulati o n (as defi ne d i n Secti o n 4 ) 
as descri be d i n Secti o n 5. 2. 1 or Secti o n 5. 2. 2 (as a p pr o priate).
6. 5. 2. St u d y C o n d uct a n d P artici p a nt Dis p ositi o n
Partici pa nt e val uati o n gr o u ps will s h o w partici pa nt dis p ositi o n b y  d ose a n d treat me nt (if 
a p plica ble) a n d o verall a n d will s h o w w hic h partici pa nts were a nal yz e d f or P K a n d safet y . 
Fre q ue nc y  c o u nts a n d perce nta ges will be s u p plie d f or partici pa nt disc o nti n uati o n(s) b y 
treat me nt. Data will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds.
6. 5. 3. St u d y Tre at me nt E x p os ure
N ot a p plica ble.
6. 5. 4. C o nc o mit a nt Me dic ati o ns a n d N o n dr u g T re at me nts
All pri or a n d c o nc o mita nt me dicati o n(s) as well as n o n -dr u g treat me nt(s) will be re p orte d 
acc or di n g t o c urre nt s p o ns or re p orti n g sta n dar ds.
6. 5. 5. S pecifie d Ge netics 
Ge n ot y pi n g or p har mac o ge n o mic data fr o m s pecifie d ge netics 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 y ses. T he res ults of s uc h a nalys es are n ot 
pla n ne d t o be i ncl u de d i n t he C S R.
6. 5. 6. Ot her E x pl or at or y Bi o m ar kers
Circ ulat or y  bi o mar ker data fr o m s pecifie d pr otei n 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 y ses. The res ults of s uc h a nal yses are n ot pla n ne d 
t o be i ncl u de d i n t he C S R.
6. 6. S afet y S u m m aries a n d A n al yses
See Secti o n 6. 1 . 
7. I N T E RI M A N A L Y S E S
7. 1. I ntr o d ucti o n
N o f or m al i nteri m a n alysis will be c o n d ucte d f or t his st u dy.
H o we ver, preli mi nar y  draft safety a n d P K data will be re vie we d after eac h st u d y  peri o d. T his 
is a s p o ns or-o pe n st u d y, wit h t he i n vesti gat or a n d partici pa nt bli n de d t o st u d y  treat me nt. A 
li mite d n u m ber of Pfizer pers o n nel (e g, P K assa y s pecialist, me dical m o nit or, cli nical lea d, 
st u d y cli nicia n, statisticia n, cli nical pr o gra m mer, a n d cli nical p har mac ol o g y lea d) will be 
u n bli n de d t o treat me nts i n or der t o per mit real -ti me i nter pretati o n of t he safet y a n d 
p har mac o ki netic data, a n d t o pr o vi de i nf or mati o n necessar y  f or d ose escalati o n decisi o ns a n d 
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 3 of 2 7
t o p ote ntiall y alter t he d ose escalati o n se q ue nce. T o mi ni mize t he p ote ntial f or bias, treat me nt 
ra n d o mizati o n i nf or mati o n will be ke pt c o nfi de ntial b y Pfizer pers o n nel a n d will n ot be 
release d t o t he i n vesti gat or/st u d y staff u ntil t he c o ncl usi o n of t he st u d y. U n bli n di n g will n ot 
be perf or me d u ntil t he fi nal data base has bee n l oc ke d f or all c o h orts. Fi nal a nal ys is will 
f oll o w t he official data base release.
7. 2. I nteri m A n al yses a n d S u m m aries
N ot a p plica ble.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 4 of 2 7
A P P E N DI C E S
A p pe n di x 1. C ate g oric al Cl asses f or E C G a n d Vit al Si g ns of P ote nti al Cli nic al C o ncer n
C ate g ories f or Q Tc F
A bs ol ute val ue of Q Tc F ( msec)
4 5 0 a n d 4 8 0
> 4 8 0 a n d 5 0 0
> 5 0 0
I ncrease fr o m baseli ne i n Q Tc F ( msec)
3 0 a n d 6 0
> 6 0
C ate g ories f or P R a n d Q R S
P R ( ms ec)
ma x. ≥3 0 0
P R ( ms ec) i ncrease fr o m baseli ne
Baseli ne > 2 0 0 a n d ma x. ≥2 5 % 
i ncrease
Baseli ne ≤2 0 0 a n d ma x. ≥5 0 % 
i ncrease
Q R S ( ms ec)
ma x. ≥1 4 0
Q R S ( ms ec) i ncrease fr o m 
baseli ne
≥5 0 % i ncrease
C ate g ories f or Vit al Si g ns
S y st olic B P ( m m H g)
mi n. < 9 0
S y st olic B P ( m m H g) c ha n ge fr o m baseli ne
ma x. decrease ≥3 0
ma x. i ncrease ≥3 0
Diast olic B P ( m m H g)
mi n. < 5 0
Diast olic B P ( m m H g) c ha n ge fr o m baseli ne
ma x. decrease ≥2 0
ma x. i ncrease ≥2 0
S u pi ne p ulse rate ( b p m)
mi n. < 4 0
ma x. > 1 2 0
Meas ure me nts t hat f ulfill t hese criteria are t o be liste d i n t he re p ort.
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 5 of 2 7
A p pe n di x 2.
E x a m ple S A S C o de f or St atistic al A n al yses
pr oc mi xe d data = dataset;
class s u bji d trt;
m o del & var = trt /resi d ual d df m = kr ;
ra n d o m s u bji d;
ls mea ns trt / diff cl al p ha = 0. 1;
r u n;
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 6 of 2 7
A p pe n di x 3.
List o f A b bre vi ati o ns
A b bre vi ati o n
Ter m
A E
A d verse e ve nt
A U C
A rea u n der t he c ur ve
A U C 2 4
Area u n der t he c ur ve fr o m ti me zer o t o 2 4 h o urs
A U C e xtra p %
Perce nt of A U C i nf base d o n e xtra p olati o n
A U C i nf
Area U n der t he C o nce ntrati o n-Ti me C ur ve fr o m ti me zer o 
e xtra p olate d t o i nfi nit y
A U C i nf ( d n)
D ose n or malize d area U n der t he C o nce ntrati o n-Ti me C ur ve fr o m 
ti me zer o e xtra p olate d t o i nfi nit y
A U C last
Area U n der t he C o nce ntrati o n -Ti me C ur ve fr o m ti me zer o t o t he last 
meas ura ble c o nce ntrati o n
A U C last ( d n)
D ose n or malize d area U n der t he C o nce ntrati o n-Ti me C ur ve fr o m 
ti me zer o t o t he last meas ura ble c o nce ntrati o n
B L Q
B el o w t he li mit of q ua ntitati o n
B P
B l o o d press ure
b p m
Beats per mi n ute
C F B
C ha n ge fr o m Baseli ne
CI
C o nfi de nce i nter val
C L  
Cleara nce
C last
Last q ua ntifia ble c o nce ntrati o n
C L / F 
A p pare nt t otal b o d y cleara nce
C ma x
Ma xi m u m o bser ve d c o nce ntrati o n
C ma x ( d n)
D ose n or malize d ma xi m u m o bser ve d c o nce ntrati o n
C R F
C ase re p ort f or m
C S R
C li nical st u d y re p ort
C V
C oefficie nt of Variati o n
E C G
E lectr ocar di o gra m
E T
Earl y ter mi nati o n
I D
I de ntificati o n
k el
Eli mi nati o n rate c o nsta nt
L L O Q
L o wer li mit of q ua ntitati o n
l n
Nat ural l o g
ma x
Ma xi m u m
mi n
Mi ni m u m
m m H g
Milli meter of merc ur y
msec
Millisec o n d
N
N u m ber of partici pa nts
N/ A
n ot a p plica ble
N C
N ot Calc ulate d
N D
N ot D o ne
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)
C CI
C CI


Pr ot oc ol C 5 1 7 1 0 0 1 (P F -0 7 2 9 3 8 9 3 ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 Statistical A nal ysis Pla n Te m plate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 7 of 2 7
A b bre vi ati o n
Ter m
N S
N o Sa m ple
P A C L
Pr ot oc ol A d mi nistrati ve C ha n ge Letter
P K
P har mac o ki netic(s)
Q Tc
C orrecte d Q T
Q Tc F
C orrecte d Q T ( Fri dericia met h o d)
R E M L
Restricte d ma xi m u m li keli h o o d
S A E
Seri o us a d verse e ve nts
S A P
Statistical a nal y sis pla n
S D D
S pra y  drie d dis persi o n
sec
Sec o n d
S o A
Sc he d ule of Acti vities
T E A E
Treat me nt -E mer ge nt A d verse E ve nt
T last
Ti me of last me as ura ble c o nce ntrati o n
T ma x 
Ti me t o ma xi m u m o bser ve d c o nce ntrati o n
t ½ 
Half life
Vz/ F 
A p pare nt v ol u me of distri b uti o n
0 9 0 1 7 7 e 1 a 0 4 d 6 8f 5\ Fi n al\ Fi n al O n: 2 8- M ar- 2 0 2 4 0 8: 1 8 ( G M T)