A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY-STATE DOSE LEVELS OF PF-07081532 ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, OMEPRAZOLE AND AN ORAL CONTRACEPTIVE, AND THE EFFECT OF STEADY-STATE SEMAGLUTIDE ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, IN OBESE ADULT FEMALE PARTICIPANTS
Phase: PHASE1
Conditions: Obesity
Sponsor: Pfizer

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1
A P H A S E 1, O P E N -L A B E L, FI X E D -S E Q U E N C E S T U D Y T O E V A L U A T E T H E 
E F F E C T O F T W O S T E A D Y -S T A T E D O S E L E V E L S O F P F - 07 0 8 1 5 3 2 O N T H E 
P H A R M A C O KI N E TI C S O F SI N G L E -D O S E MI D A Z O L A M , O M E P R A Z O L E A N D 
A N O R A L C O N T R A C E P TI V E, A N D T H E E F F E C T O F S T E A D Y -S T A T E 
S E M A G L U TI D E O N T H E P H A R M A C O KI N E T I C S O F SI N G L E-D O S E 
MI D A Z O L A M , I N O B E S E A D U L T F E M A L E 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 - 07 0 8 1 5 3 2
St u d y I nter ve nti o n N a me:
N/ A
U S I N D N u m ber:
1 6 0 2 9 6 ( P F-0 7 0 8 1 5 3 2)
E u dr a C T N u m ber:
N/ A
Cli nic al Tri als. g o v I D:  
N/ A
Pr ot oc ol N u m ber:
C 3 9 9 1 0 4 0
P h ase:
1
Brief Title : A P hase 1 , 2-C o h ort , Fi xe d-Se q ue nce St u d y  to E val uate the Effect o f 2
Stea d y -State D oses of P F - 07 0 8 1 5 3 2 o n Si n gle -D ose Mi daz ola m , O me praz ole , a n d Oral 
C o ntrace pti ve P har mac o ki netics , a n d t he Effect of S e ma gl uti de o n Si n gle -D ose 
Mi daz ola m
P har mac o ki netics , i n O bese A d ult Fe male Partici pa nt s.
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 os es. 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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
Ori gi nal Pr ot oc ol
0 7 N o ve m ber 2 0 2 2
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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
1. P R O T O C O L  S U M M A R Y...................................................................................................1 0
1. 1. S y n o psis ..................................................................................................................1 0
1. 2. Sc he ma ....................................................................................................................1 5
1. 3. Sc he d ule of Acti vities .............................................................................................1 5
2. I N T R O D U C TI O N ...............................................................................................................3 0
2. 1. St u d y  Rati o nale .......................................................................................................3 0
2. 2. Bac k gr o u n d .............................................................................................................3 0
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................3 1
2. 2. 2. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 3 1
2. 2. 3. N o ncli nical Safet y ...................................................................................... 3 2
2. 2. 4. Cli nical O ver vie w a n d Safet y..................................................................... 3 2
2. 2. 4. 1. Cli nical P har mac o ki netics .........................................................3 3
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................3 3
2. 3. 1. Ris k Assess me nt......................................................................................... 3 4
2. 3. 2. Be nefit Assess me nt .....................................................................................3 6
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................3 7
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................3 7
4. S T U D Y D E SI G N .................................................................................................................3 9
4. 1. O verall Desi g n .........................................................................................................3 9
4. 1. 1. C o h ort 1 ......................................................................................................4 0
4. 1. 2. C o h ort 2 ......................................................................................................4 0
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................4 1
4. 2. 1. C o h ort 1 ......................................................................................................4 1
4. 2. 1. 1. Mi daz ola m A d mi nistrati o n .......................................................4 1
4. 2. 1. 2. O me praz ole A d mi nistrati o n ......................................................4 3
4. 2. 1. 3. Oral C o ntrace pti ve A d mi nistrati o n................................ ...........4 3
4. 2. 1. 4. P F -0 7 0 8 1 5 3 2 A d mi nistrati o n ....................................................4 4
4. 2. 2. C o h ort 2 ......................................................................................................4 4
4. 2. 2. 1. Se ma gl uti de a n d Mi daz ola m A d mi nistrati o n............................ 4 4
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4
4. 2. 3. Safet y Assess me nts ( C o h orts 1 a n d 2) ........................................................4 6
4. 2. 4. Di versit y  of St u d y P o p ulati o n ....................................................................4 7
4. 2. 5. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................4 7
4. 2. 6. C ollecti o n of Retai ne d Researc h Sa m ples ..................................................4 7
4. 3. J ustificati o n f or D ose ..............................................................................................4 7
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................4 9
5. S T U D Y P O P U L A T I ON................................ ......................................................................4 9
5. 1. I ncl usi o n Criteria .....................................................................................................4 9
5. 2. E xcl usi o n Criteria ....................................................................................................5 0
5. 3. L ifest yle C o nsi derati o ns..........................................................................................5 4
5. 3. 1. Meals a n d Dietar y  Restricti o ns...................................................................5 4
5. 3. 2. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................5 5
5. 3. 3. Acti vit y .......................................................................................................5 6
5. 3. 4. C o ntrace pti o n ..............................................................................................5 6
5. 4. Scree n Fail ures ........................................................................................................5 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 .................................5 6
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................5 7
6. 1. 1. A d mi nistrati o n ............................................................................................5 7
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................5 9
6. 2. 1. Pre parati o n a n d Dis pe nsi n g........................................................................ 6 0
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................6 0
6. 4. Bli n di n g................................ ...................................................................................6 2
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................6 2
6. 6. D ose M o dificati o n ...................................................................................................6 2
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 ......................6 2
6. 8. Treat me nt of O ver d ose................................ ............................................................6 3
6. 9. C o nc o mita nt T hera p y ..............................................................................................6 3
6. 9. 1. Resc ue Me dici ne .........................................................................................6 4
6. 9. 1. 1. Ma na ge me nt of Na usea a n d V o miti n g ......................................6 4
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 ...........................................................................6 5
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................6 5
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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 ........................................6 5
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................6 6
7. 3. L ost t o F oll o w - u p....................................................................................................6 7
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 ...............................................................6 7
8. 1. A d mi nistrati ve Pr oce d ures ......................................................................................6 7
8. 2. Efficac y  Assess me nts..............................................................................................6 8
8. 3. Safet y Assess me nts .................................................................................................6 8
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................6 8
8. 3. 2. Vital Si g ns ..................................................................................................6 9
8. 3. 2. 1. T e m perat ure ..............................................................................7 0
8. 3. 3. Electr ocar di o gra ms..................................................................................... 7 0
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................7 1
8. 3. 4. 1. Alter nati ve Facilities f or Cli nical Safet y  La b orat or y 
Assess me nt ........................................................................................7 1
8. 3. 5. C O VI D - 1 9 S pecific Assess me nts...............................................................7 2
8. 3. 6. Ma na ge me nt of H y p o gl y ce mia ...................................................................7 2
8. 3. 6. 1. Defi niti o n a n d Se verit y of Cate g orizati o n of 
H y p o gl yc e mic A d verse E ve nt ( H A E) ...............................................7 2
8. 3. 6. 2. Gl uc o meter M o nit ori n g of Gl uc ose ................................ ..........7 3
8. 3. 7. Pre g na nc y  Testi n g ......................................................................................7 4
8. 3. 8. S uici dal I deati o n a n d Be ha vi or Ris k M o nit ori n g .......................................7 4
8. 3. 8. 1. C ol u m bia S uici de Se verit y Rati n g Scale ( C -S S R S) .................7 4
8. 3. 8. 2. Patie nt Healt h Q uesti o n naire- 9 ( P H Q - 9) ..................................7 5
8. 3. 8. 3. Referral t o a Me ntal Healt h Pr ofessi o nal ..................................7 5
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 .................7 5
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......7 6
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................7 7
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 ...................7 7
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................7 7
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................7 7
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................7 8
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 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 .....................................................7 8
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................7 8
8. 4. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................ 8 0
8. 4. 5. 3. Occ u pati o nal E x p os ure ............................................................. 8 0
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................8 0
8. 4. 7. Disease -Relate d E ve nts a n d/ or Disease -Relate d O utc o mes N ot 
Q ualif y i n g as A Es or S A Es .............................................................................. 8 0
8. 4. 8. A d verse E ve nts of S pecial I nterest ............................................................. 8 0
8. 4. 8. 1. Lac k of Efficac y ........................................................................ 8 1
8. 4. 9. Me dical De vice Deficie ncies ...................................................................... 8 1
8. 4. 1 0. Me dicati o n Err ors ..................................................................................... 8 1
8. 5. P har mac o ki netics .................................................................................................... 8 1
8. 5. 1. P K of Mi daz ola m a n d 1- h y dr o x y m i daz ola m ............................................. 8 3
8. 5. 2. P K of O me praz ole a n d 5 -h y dr o x y o me praz ole ........................................... 8 3
8. 5. 3. P K of Le v o n or gestrel .................................................................................. 8 3
8. 5. 4. P K of Et hi n y l Estra di ol............................................................................... 8 3
8. 5. 5. P K of P F -0 7 0 8 1 5 3 2 .................................................................................... 8 3
8. 5. 6. P K of Se ma gl uti de ...................................................................................... 8 3
8. 6. Ge netics ................................................................................................................... 8 4
8. 6. 1. S pecifie d Ge netics ...................................................................................... 8 4
................................................... 8 4
8. 7. Bi o mar kers .............................................................................................................. 8 4
8. 7. 1. S pecifie d Pr otei n Researc h .........................................................................8 4
8. 7. 2. S pecifie d Ge ne E x pressi o n ( R N A) Researc h .............................................8 4
8. 7. 3. S pecifie d Meta b ol o mic Researc h ...............................................................8 4
8. 7. 4. Retai ne d Researc h Sa m ples f or Bi o mar kers ...............................................8 4
8. 7. 5. Plas ma f or A nal ys is of 4-h y dr o x y c h olester ol/c h olester ol ........................ 8 5
8. 8. I m m u n o ge nicit y Assess me nts ................................................................................. 8 5
8. 9. Healt h Ec o n o mics ................................................................................................... 8 5
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................8 5
9. 1. Statistical H y p ot heses ............................................................................................. 8 5
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7
9. 2. A nal y sis Sets ...........................................................................................................8 5
9. 3. Statistical A nal y ses .................................................................................................8 6
9. 3. 1. Ge neral C o nsi derati o ns ...............................................................................8 6
9. 3. 1. 1. Deri vati o n of P har mac o ki netic Para meters ...............................8 6
9. 3. 2. Statistical Met h o ds f or P har mac o ki netic Data ........................................... 8 8
9. 3. 3. Safet y A nal ys es ..........................................................................................9 0
9. 3. 3. 1. Electr ocar di o gra m A nal y ses......................................................9 1
9. 3. 4. Ot her A nal ys e(s) .........................................................................................9 1
9. 4. I nteri m A nalys es .....................................................................................................9 1
9. 5. Sa m ple Size Deter mi nati o n .....................................................................................9 1
9. 6. Data M o nit ori n g C o m mittee or Ot her I n de pe n de nt O versi g ht C o m mittee .............9 2
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ..........................................................................9 3
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............9 3
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................9 3
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................9 3
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................9 4
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................9 4
1 0. 1. 4. Data Pr otecti o n .........................................................................................9 5
1 0. 1. 5. C o m mittees Str uct ure ...............................................................................9 5
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ...................................................9 5
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ......................................................9 5
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................9 7
1 0. 1. 8. S o urce D oc u me nts ....................................................................................9 8
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................9 8
1 0. 1. 1 0. P u blicati o n P olic y ...................................................................................9 9
1 0. 1. 1 1. S p o ns or’s Q ualifie d Me dical P ers o n nel ............................................... 1 0 0
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests...............................................................1 0 1
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -U p, a n d Re p orti n g ...................................................................1 0 3
1 0. 3. 1. Defi niti o n of A E .....................................................................................1 0 3
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8
1 0. 3. 2. Defi ni ti o n of a n S A E.............................................................................. 1 0 4
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w -U p of A Es a n d/ or S A Es D uri n g 
t he Acti ve C ollecti o n Peri o d.......................................................................... 1 0 6
1 0. 3. 4. Re p orti n g of S A Es .................................................................................. 1 0 9
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce .............................................. 1 1 0
1 0. 4. 1. Male ........................................................................................................ 1 1 0
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria ............................... 1 1 0
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial .......................................................... 1 1 0
1 0. 4. 4. C o ntrace pti o n Met h o ds ........................................................................... 1 1 1
.......................................................................................... 1 1 3
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts ..... 1 1 4
1 0. 7. A p pe n di x 7: Ki d ne y  Safet y M o nit ori n g G ui deli nes ........................................... 1 1 6
1 0. 7. 1. La b orat or y  Assess me nt of C ha n ge i n Ki d ne y F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y ............................................................................ 1 1 6
1 0. 7. 2. A g e-S pecific Ki d ne y  F u ncti o n Calc ulati o n Rec o m me n dati o ns............. 1 1 6
1 0. 7. 2. 1. A d ults ( 1 8 Years a n d A b o ve) -2 0 2 1 C K D -E PI  E q uati o ns..... 1 1 6
1 0. 7. 3. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ................................................................................................. 1 1 6
1 0. 8. A p pe n di x 8: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ................................. 1 1 7
1 0. 9. A p pe n di x 9 A b bre viati o ns .................................................................................. 1 1 9
1 1. R E F E R E N C E S ................................................................................................................ 1 2 4
LI S T O F T A B L E S
Ta ble 1.
C o h ort 1 - O verall Sc he d ule of Acti vities Scree ni n g t o Peri o d 5 ............. 1 6
Ta ble 2.
C o h ort 1 - O verall Sc he d ule of Acti vities Peri o d 6 t o E T ........................ 1 9
Ta ble 3.
Sc he d ule of Acti vities – Da y  1 of Peri o d 1 ( Mi daz ola m + 
O me praz ole O N L Y), Peri o d 4 ( Mi daz ola m + O me praz ole + 
P F - 0 7 0 8 1 5 3 2 8 0 m g Q D), Peri o d 7 ( Mi daz ola m + O me praz ole + 
P F - 0 7 0 8 1 5 3 2 2 6 0 m g Q D), a n d Peri o d 9 ( Mi daz ola m O N L Y) ............... 2 2
Ta ble 4.
Sc he d ule of Acti vities – Da y  1 of Peri o d 2 ( O C O N L Y), Peri o d 5 
( O C + P F- 0 7 0 8 1 5 3 2 8 0 m g Q D) a n d Peri o d 8 ( O C + P F - 0 7 0 8 1 5 3 2 
2 6 0 m g Q D) ..............................................................................................2 3
Ta ble 5.
Sc he d ule of Acti vities – Da y  2 8 of Peri o d 3 a n d Da y 6 3 of Peri o d 6 
( P F- 0 7 0 8 1 5 3 2 o nly) .................................................................................. 2 4
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9
Ta ble 6.
C o h ort 2: Sc he d ule of Acti vities ...............................................................2 5
Ta ble 7.
Sc he d ule of Acti vities – Da y  1 of Peri o d 1 ( Mi daz ola m O N LY), 
Peri o d 3 ( Mi daz ola m + Se ma gl uti de 2. 4 m g), a n d Peri o d 4 
( Mi daz ola m O N L Y) .................................................................................2 9
Ta ble 8.
C o h ort 1 D osi n g ........................................................................................5 8
Ta ble 9.
C o h ort 2 D osi n g ........................................................................................5 9
Ta ble 1 0.
P F -0 7 0 8 1 5 3 2 D osi n g Re gi me ns i n C o h ort 1 ............................................6 1
Ta ble 1 1.
Se ma gl uti de D osi n g Re gi me ns i n C o h ort 2 ..............................................6 2
Ta ble 1 2.
Plas ma P K Para meters f or Mi daz ola m, 1- O H -Mi daz ola m, 
O me praz ole, 5 -O H -O me praz ole, Le v o n or gestrel a n d Et hi n y l 
Estra di ol ....................................................................................................8 7
Ta ble 1 3.
Plas ma P K Para meters f or P F- 0 7 0 8 1 5 3 2 ................................................. 8 8
Ta ble 1 4.
E x pecte d Wi dt hs of t he 9 0 % CI s ( wit h 8 0 % C o vera ge Pr o ba bilit y) 
f or Differe nt P ossi ble Esti mate d Effects a n d Para meters of I nterest .......9 2
Ta ble 1 5.
Pr ot oc ol -Re q uire d Safet y L a b orat or y Assess me nts ...............................1 0 1
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Brief Title: A P hase 1 , 2-C o h ort, Fi xe d -Se q ue nce St u d y  to E val uate the Effect o f 
2 Stea d y -State D oses of P F - 0 7 0 8 1 5 3 2 o n Si n gle - D ose Mi daz ola m, O me praz ole, a n d Oral 
C o ntrace pti ve P har mac o ki netics , a n d t he Effect of Se ma gl uti de o n Si n gle - D ose Mi daz ola m 
P har mac o ki netics, i n O bese A d ult Fe male Partici pa nts .
R ati o n ale
T his is a P hase 1, o pe n -la bel, fi xe d-se q ue nce, 2- c o h ort st u d y t o e val uate t he effect of 
1) 2 stea dy- state d ose le vels of P F - 0 7 0 8 1 5 3 2 o n t he S D p har mac o ki netics of mi daz ola m , 
o me praz ole, a n d a n O C ( L E/ E E), a n d 2) stea d y-state se ma gl uti de o n t he S D 
p har mac o ki netics of mi daz ola m, i n ot her wise healt h y  o bese a d u lt fe male partici pa nts . T he 
i nte nt of t his st u d y is 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 .
O bjecti ves a n d E n d p oi nts
O bjecti ves
E n d p oi nts
C o h ort 1
Pri m ar y: 
Pri m ar y: 

T o e val uate t he effects of P F -0 7 0 8 1 5 3 2 o n t he 
p har mac o ki netics of mi daz ola m, o me praz ole, 
a n d a n oral c o ntrace pti ve ( O C; L E/ E E) i n o bese 
a d ult fe male partici pa nts.

Mi daz ola m plas ma p har m ac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o ds 1, 4 a n d 7.

O m e praz ole plas ma p har mac o ki netic 
para meters: A U C i nf (if data per mit* ot her wise 
A U C last) i n Peri o ds 1, 4 a n d 7.

L E plas ma p har mac o ki netic para meters: A U C i nf
(if data per mit* ot her w ise A U Clast) i n Peri o ds 2, 
5 a n d 8.

E E plas ma p har mac o ki netic para meters: A U C i nf
(if data per mit* ot her wise A U C last) i n i n Peri o ds 
2, 5 a n d 8.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
P F - 07 0 8 1 5 3 2 a d mi nistere d se paratel y a n d i n 
c o m bi nati o n wit h mi daz ola m, o me praz ole, a n d 
a n O C ( L E/ E E) i n o bese a d ult fe male 
partici pa nts .

Assess me nt of T E A Es , cli nical la b orat or y 
a b n or malities, a n d b o d y wei g ht .

Assess me nt of me ntal healt h as deter mi ne d b y 
C- S S R S a n d P H Q - 9. 

T o e val uate t he p har mac o ki netics of S D 
mi daz ola m f oll o wi n g t he disc o nti n uati o n of 
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n i n o bese a d ult 
fe male partici pa nts.  

Mi daz ola m plas ma p har mac o ki netic para meters:
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o d 9.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n 
a d diti o nal p har mac o ki netic para meters of 
mi daz ola m , o me praz ole, a n d a n O C ( L E/ E E) i n 
o bese a d ult fe male partici pa nts.

A d diti o nal plas ma p har mac o ki netic para meters 
f or mi daz ola m a n d o me praz ole ( Peri o ds 1, 4 a n d 
7) , a n d L E a n d E E ( Peri o ds 2, 5 a n d 8): Cma x a n d 
T ma x ; a n d C L/ F, Vz/ F, t½ , as data per mit.

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n t he 
meta b olite/ p are nt rati os f or mi daz ola m a n d 
o m e praz ole i n o bese a d ult fe male partici pa nts.

M R A U C
i nf ( 1-h y dr o x y mi daz ola m 
A U C i nf/ mi daz ola m A U Ci nf).

M R A U C
i nf ( 5-h y dr o x y o m e praz ole
A U C i nf/o m e praz ole A U C i nf).

T o e val uate t he M D p har mac o ki netics of 
P F - 07 0 8 1 5 3 2 i n o bese a d ult fe male partici pa nts.

P F - 07 0 8 1 5 3 2 plas ma p har mac o ki netic 
para meters at Da ys 3 4 a n d 1 0 3: A U C 2 4, Cma x , 
T ma x .
C o h ort 2
Pri m ar y: 
Pri m ar y: 

T o e val uate t he effects of se ma gl uti de 
(s u bc uta ne o us se ma gl uti de) o n t he S D P K of 
mi daz ola m i n o bese a d ult fe male partici pa nts.

Mi daz ola m plas ma p har mac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o ds 1 a n d 3.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
se ma gl uti de a d mi nistere d se paratel y a n d i n 
c o m bi nati o n wit h mi daz ola m i n o bese a d ult 
fe male partici pa nts.

Assess me nt of T E A Es , cli nical la b orat or y 
a b n or malities, a n d b o d y wei g ht .

Assess me nt of me ntal healt h as deter mi ne d b y 
C- S S R S a n d P H Q -9.

T o e val uate t he p har mac o ki netics of S D 
mi daz ola m f oll o wi n g t he disc o nti n uati o n of 
se ma gl uti de a d mi nistrati o n i n o bese a d ult 
fe male partici pa nts.

Mi daz ola m plas ma p har mac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o d 4.

T o e val uate t he effects of se ma gl uti de o n 
a d diti o nal p har mac o ki netic para meters of 
mi daz ola m i n o bese a d ult fe male partici pa nts.

A d diti o nal plas m a p har m ac o ki netic para meters 
f or mi daz ola m (i n Peri o ds 1 a n d 3): Cma x , Tma x ,
a n d C L/ F, Vz/ F, t ½ as data per mit.

T o e val uate t he effects of se ma gl uti de o n t he 
meta b olite/ pare nt rati o f or mi daz ola m i n o bese 
a d ult fe male partici pa nts.

M R A U C
i nf ( 1-h y dr o x y mi daz ola m 
A U C i nf/ mi daz ola m A U Ci nf).
* S h o ul d it be dee me d t hat t o o fe w A U C i nf esti mates (e g, less t ha n 1 2 f or a si n gle treat me nt) are o btai ne d 
fr o m t he e val ua ble partici pa nts, A U Clast ma y be selecte d as t he pri mar y e n d p oi nt f or C S R re p orti n g.  T his 
will be c o nsi dere d f or t he mi daz ola m, 1 -h y dr o x y mi daz ola m, o me praz ole, 5 -h y dr o x y o me pr az ole, L E, a n d E E 
o bjecti ves se paratel y.
O ver all Desi g n
Brief S u m m ar y
T his st u d y  is a P hase 1, o pe n-la bel st u dy t hat will be c o n d ucte d i n 2 c o h orts; b ot h c o h orts 
will e nr oll ot her wise healt h y , o bese , a d ult fe male partici pa nts . C o h ort 1 is a n o pe n-la bel, 
9 -peri o d, fi xe d-se q ue nce desi g n t o e val uate t he effect of 2 stea dy-state d ose le vels of 
P F - 0 7 0 8 1 5 3 2 o n t he S D p har mac o ki netics of mi daz ola m a n d o me praz ole, a d mi nistere d
si m ulta ne o usl y, a n d a n O C ( LE/ E E) . C o h ort 2 is a n o pe n-la bel, 4 -peri o d, fi xe d-se q ue nce
desi g n t o e val uate t he effect of stea dy- state se ma gl uti de o n t he S D p har mac o ki netics of
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2
m i daz ola m. A d diti o nall y, partici pa nts i n b ot h c o h orts will be disc har ge d fr o m t he cli nical 
site f or 2 wee ks f oll o wi n g t he fi nal P K sa m ple c ollecti o n of O C ( L E/ E E) i n Peri o d 8, Da y 2 
( C o h ort 1) or mi daz ola m i n Peri o d 3, Da y 2 ( C o h ort 2), a n d disc o nti n ue all f urt her 
P F - 0 7 0 8 1 5 3 2 or se ma gl uti de d osi n g at t hat ti me.  F oll o wi n g t he 2-wee k o ut -patie nt d urati o n, 
partici pa nts will ret ur n t o t he cli nical site f or a fi nal mi daz ol a m assess me nt ( wit h o ut eit her 
P F -0 7 0 8 1 5 3 2 or se ma gl uti de c oa d mi nistrati o n ).
Partici pa nts will partici pate i n eit her C o h or t 1 or C o h ort 2 ( n ot b ot h), a n d C o h ort 1 a n d 
C o h ort 2 are preferre d t o be c o n d ucte d i n parallel, if p ossi ble. F or partici pa nts i n C o h ort 1, 
t he t otal d urati o n of partici pati o n fr o m t he Scree ni n g Visit t o t he F/ U c o ntact will be 
a p pr o xi matel y 1 8 8 d a y s or 2 7 wee ks. F or partici pa nts i n C o h ort 2, t he t otal d urati o n of 
partici pati o n fr o m t he Scree ni n g Visit t o t he F/ U c o ntact will be a p pr o xi matel y 2 2 8 d a y s or 
3 3 wee ks.
N u m ber of P artici p a nts
A sa m ple size of a p pr o xi matel y 1 6 partici pa nts i n C o h ort 1 a n d a p pr o xi matel y
1 6 partici pa nts i n C o h ort 2 will be e nr olle d s uc h t hat a p pr o xi matel y  1 2 e val ua ble partici pa nts 
c o m plete eac h c o h ort of t he st u d y.  
P ote ntial partici pa nts w h o are scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y  f or t he 
st u d y, b ut d o n ot partici pate i n t he st u d y, are n ot c o nsi dere d e nr olle d, u nless ot her wise 
s pecifie d by t he pr ot oc ol.
N ote: " E nr olle d" mea ns a partici pa n t's a gree me nt t o partici pate i n a cli nical st u d y f oll o wi n g 
c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d scree ni n g. A partici pa nt will be c o nsi dere d 
e nr olle d if t he i nf or me d c o nse nt is n ot wit h dra w n pri or t o partici pati n g i n a n y  st u d y acti vit y 
after scre e ni n g. 
I nter ve nti o n Gr o u ps a n d D ur ati o n
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 0 8 1 5 3 2, mi daz ola m, 
o me praz ole, O C a n d se ma gl uti de .
T he p ur p ose of t his st u d y is t o c haracterize t he effect of P F - 0 7 0 8 1 5 3 2, a d mi nistere d at 
2 stea d y-state d ose le vels, o n t he P K of si n gle d oses of mi daz ola m ( 2 m g oral ) a n d 
o me praz ole ( 2 0 m g oral ), a d mi nistere d si m ulta ne o usl y, a n d a n O C ( L E 0. 1 5 m g/ E E 0. 0 3 m g
oral ) i n ot her wise healt h y , o bese , a d ult fe male partici pa nts i n C o h ort 1.  A d diti o nall y , 
C o h ort 2 will c haracterize t he effect of se ma gl uti de ( 2. 4 m g s u bc uta ne o us) a d mi nistere d t o 
stea d y state o n t he P K of si n gle d oses of mi daz ola m ( 2 m g) i n ot her wise healt h y , o bese , a d ult 
fe male partici pa nts. Titrati o n of P F - 0 7 0 8 1 5 3 2 a n d se ma gl uti de d oses will be utilize d t o 
ac hie ve a ma xi m u m d ose of 2 6 0 m g Q D i n C o h ort 1 (Ta ble 8 ) a n d 2. 4 m g ( gi ve n o nce 
wee kl y) i n C o h ort 2 (Ta ble 9 ), res pecti vel y.
A d diti o nall y , partici pa nts i n b ot h c o h orts will be disc har ge d fr o m t he cli nical site f or 2 wee ks 
f oll o wi n g t he fi nal P K sa m ple c ollecti o n of O C ( L E/ E E) i n Peri o d 8, Da y 2 ( C o h ort 1) or 
mi daz ola m i n Peri o d 3, Da y  2 ( C o h ort 2), a n d disc o nti n ue all f urt her P F-0 7 0 8 1 5 3 2 or 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3
se ma gl uti de d osi n g at t hat ti me.  F oll o wi n g t he 2-wee k o ut -patie nt d urati o n, partici pa nts will 
ret ur n t o t he cli nical site f or a fi nal mi daz ola m assess me nt ( wit h o ut eit her P F-0 7 0 8 1 5 3 2 or 
se ma gl uti de c oa d mi nistrati o n).  I n C o h ort 1, the dr u g - dr u g i nteracti o n effect will be assesse d 
at P F - 0 7 0 8 1 5 3 2 d oses of 8 0 m g Q D a n d 2 6 0 m g Q D , as 8 0 m g Q D is pr ojecte d as a p ote ntial 
t hera pe utic d ose f or T 2 D M a n d 2 6 0 m g Q D is t he ma xi m u m d ose bei n g st u die d i n P hase 2 
f or T 2 D M a n d o besit y . I n C o h ort 2, t he D DI effect will be assesse d at a se ma gl uti de d ose of 
2. 4 m g as t his is t he ma xi m u m a p pr o ve d d ose f or wei g ht l oss. I n b ot h c o h orts, t he i m pact of 
disc o nti n uati o n f or 2 wee ks of eit her P F - 0 7 0 8 1 5 3 2 ( C o h ort 1) or se ma gl uti de ( C o h ort 2) o n 
t he P K of mi daz ola m will be assesse d. 
P F - 0 7 0 8 1 5 3 2 will be pr o vi de d as ta blets f or oral a d mi nistrati o n.  St u d y i nter ve nti o n 
(P F - 0 7 0 8 1 5 3 2), mi daz ola m a n d o me praz ole or t he O C m ust be a d mi nistere d wit hi n 
a p pr o xi matel y 1 0 mi n utes of c o m pleti o n of t he m or ni n g meal w he n ta ke n al o ne .  
P F - 0 7 0 8 1 5 3 2 will be a d mi nistere d first a n d mi daz ola m a n d o me praz ole or t he O C will be 
a d mi nistere d wit hi n 5 mi n utes of P F - 0 7 0 8 1 5 3 2 d uri n g t he D DI assess me nt peri o ds.
S e ma gl uti de ( Oze m pic a n d/ or We g o v y) will be pr o vi de d as pre -fille d, si n gle-d ose pe ns / d ose 
le vel f or s u bc uta ne o us i njecti o n.  Dr u g a d mi nistrati o n will f oll o w t he i nstr ucti o ns pr o vi de d i n 
t he a p pr o ve d Hi g hli g hts of Prescri bi n g I nf or mati o n as o utli ne d i n t he U S PI .  St u d y  
i nter ve nti o n (se ma gl uti de) m ust be a d mi nistere d o nce wee kl y , prefera bl y i n t he m or ni n g,
wit h o ut re gar d t o ti mi n g of t he brea kfast meal d uri n g o ut patie nt visits t o t he C R U f or d ose 
a d mi nistrati o n.  D uri n g t he D DI assess me nt i n patie nt visit ( Peri o d 3) , se ma gl uti de a n d 
mi daz ola m m ust be a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes of c o m pleti o n of t he 
m or ni n g meal.  S e ma gl ut i de will be a d mi nistere d first a n d mi daz ola m will be a d mi nistere d 
wit hi n 5 mi n utes of se ma gl uti de.
C o h ort 1 : 11 2 da y s will be i n-patie nt as f oll o ws: Peri o d 1 ( S D mi daz ola m a n d o me praz ole): 
1 da y ; Peri o d 2 ( S D O C): 5 da y s; Peri o d 3 (P F -0 7 0 8 1 5 3 2 titrate d t o 8 0 m g Q D) : 28 d a y s; 
Peri o d 4 ( 8 0 m g P F -0 7 0 8 1 5 3 2 + S D mi daz ola m a n d o me praz ole ): 1 da y; Peri o d 5 ( 8 0 m g 
P F -0 7 0 8 1 5 3 2 + S D O C ): 5 da y s; Peri o d 6 ( P F -0 7 0 8 1 5 3 2 titrate d t o 2 6 0 m g Q D) : 6 3 d a y s; 
Peri o d 7 ( 2 6 0 m g P F -0 7 0 8 1 5 3 2 + S D mi daz ola m a n d o me praz ole ): 1 da y; Peri o d 8 ( 2 6 0 m g  
P F -0 7 0 8 1 5 3 2 + S D O C ): 6 da ys; Peri o d 9 ( S D mi daz ola m o nl y): 2 da ys.
C o h ort 2 : 6 da y s will be i n-patie nt as f oll o ws: Peri o d 1 ( S D mi daz ola m ): 1 da y ; Peri o d 2 
(fi nal da y of se ma gl uti de titrate d t o 2. 4 m g o nce wee kl y ): 1 da y ; Peri o d 3 ( 2. 4 m g 
se ma gl uti de o nce wee kl y + S D mi daz ola m ) 2 da y s; Peri o d 4 ( S D mi daz ola m): 2 da y s.  
Partici pa nts will als o be re q uire d t o ret ur n t o t he cli nic d uri n g o ut- patie nt visits , prefera bly i n 
t he m or ni n g, t o recei ve t heir o nce wee kly se ma gl uti de i njecti o ns ( Peri o d 2).
T h e F/ U visit will occ ur 7 -1 0 da y s fr o m t he last d ose of st u d y i nter ve nti o n a n d a tele p h o ne 
F/ U c o ntact will occ ur 2 8- 3 5 d a y s fr o m t he last d ose of st u d y i nter ve nti o n. 
D at a M o nit ori n g C o m mittee or Ot her I n de pe n de nt O versi g ht C o m mittee : 
T his st u d y will n ot use a D M C .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4
St atistic al Met h o ds
T he P K data f or P F -0 7 0 8 1 5 3 2 , mi daz ola m , 1 -h y r o x ymi daz ola m, o me praz ole,
5 -h y dr o x y o me praz ole, L E , a n d E E will be a nal yz e d a n d re p orte d se paratel y.
C o h ort 1
Nat ural l o g e tra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of o me praz ole 
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 will be a nal y ze d 
usi n g a mi xe d effect m o del wit h treat me nt as a fi xe d effect a n d partici pa nt as a ra n d o m 
effect.  Esti mates of t he a dj uste d mea n differe nces ( Tes t- Refere nce) a n d c orres p o n di n g 
9 0 % CI s will be o btai ne d fr o m t he m o dels.  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 2 test treat me nts will be 
‘ o mepraz ole a n d P F -0 7 0 8 1 5 3 2 8 0 m g Q D ’ ( Peri o d 4) a n d ‘o me praz ole a n d P F - 0 7 0 8 1 5 3 2
2 6 0 m g Q D ’ ( Peri o d 7), w hic h will be re p orte d se parately i n c o m paris o n t o t he refere nce 
treat me nt of ‘o me praz ole wit h o ut P F - 0 7 0 8 1 5 3 2’ ( Peri o d 1).  
Nat ural l o g e-tra nsf or me d A U C i nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 will be a nal y ze d 
a n d re p orte d se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or 
o me praz ole .  T he 2 test treat me nts will be ‘ mi daz ola m a n d P F - 0 7 0 8 1 5 3 2 80 m g Q D ’ 
( Peri o d 4 )’ a n d ‘ mi daz ola m a n d P F - 0 7 0 8 1 5 3 2 2 60 m g Q D ’ ( Peri o d 7 ), w hic h will be 
re p orte d se parately i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m wit h o ut 
P F - 0 7 0 8 1 5 3 2’ ( Peri o d 1 ).
Nat ural l o g e-tra nsf or me d A U C i nf (as data per mit), Cma x a n d A U C last of L E a n d E E
a d mi nistere d al o ne or c oa d mi nistere d wit h P F -0 7 0 8 1 5 3 2 will be a nal yz e d a n d re p orte d 
se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole .  F or L E , 
t he 2 test treat me nts will be ‘L E a n d P F - 0 7 0 8 1 5 3 2 80 m g Q D ’ ( Peri o d 5 ) a n d ‘L E a n d 
P F - 0 7 0 8 1 5 3 2 26 0 m g Q D ’ ( Peri o d 8 ), w hic h will be re p orte d se parately i n c o m paris o n t o t he 
refere nce treat me nt of ‘L E al o ne’ ( Peri o d 2 ). Si milarl y f or E E , t he 2 test treat me nts will be 
‘E E a n d P F - 0 7 0 8 1 5 3 2 80 m g Q D ’ ( Peri o d 5 ) a n d ‘E E a n d P F - 0 7 0 8 1 5 3 2 2 60 m g Q D ’ 
( Peri o d 8 ), w hic h will be re p orte d se parately i n c o m paris o n t o t he refere nce treat me nt of ‘ E E
al o ne’ ( Peri o d 2 ).
C o h ort 2
Nat ural l o g e-tra nsf or me d AU C i nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d al o ne or c oa d mi nistere d wit h se ma gl uti de i n C o h ort 2 will be a nalyz e d a n d 
re p orte d se parately usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole.  
T he test treat me nt will b e ‘ mi daz ola m a n d se ma gl uti de 2. 4 m g wee kl y’ ( Peri o d 3) w hic h will 
be re p orte d se paratel y i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m al o ne’ 
( Peri o d 1).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5
1. 2. Sc he m a
C o h ort 1 – P F -0 7 0 8 1 5 3 2 a n d Mi d az ol a m , O me pr az ole, a n d a n O C ( L E/ E E)
C o h ort 2 – S e m a gl uti de a n d Mi d az ol a m
N ote: f or C o h ort 2, partici pa nts will be disc har ge d fr o m t he st u d y site f oll o wi n g a d mi nistrati o n of t he first 0. 2 5 
m g se ma gl uti de i njecti o n o n Da y 1 of Peri o d 2 .  Peri o d 2 will be c o n d ucte d o ut-patie nt u ntil t he fi nal da y w he n 
partici pa nts will be rea d mitte d t o t he st u d y site t he da y pri or t o t he Peri o d 3 D DI assess me nt.  F or b ot h C o h orts 
1 a n d 2, partici pa nts will be rea d mitte d t o t he st u d y site f oll o wi n g a 2-wee k o ut -patie nt d urati o n wit h n o st u d y 
i nter ve nti o n at Peri o d 9 a n d Peri o d 4 , res pecti vel y. 
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 he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d i n 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6
C o h ort 1 : Sc he d ule of Acti vities
T a ble 1 .
C o h ort 1 - O ver all Sc he d ule of Acti vities Scree ni n g t o Peri o d 5
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble 
ma y be f o u n d i n A p pe n di x 9
Scree ni n g
Peri o d 1
(M D Z + 
O M P o nl y)
Peri o d 2
(O C o nl y )
Peri o d 3 
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 4 
( P F- 0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 5 
(P F -0 7 0 8 1 5 3 2 +
O C )
D a y i n St u d y Peri o d a
-2 8 t o - 2
- 1
1
1
2- 4
5
1
2- 7
8
9- 1 4
1 5
1 6 - 2 1
2 2
2 3 -2 7
2 8
1
1
2- 4
5
D a ys i n St u d y b
-2 8 t o - 2
- 1
1
2
3- 5
6
7
8- 1 3
1 4
1 5- 2 0
2 1
2 2 - 2 7
2 8
2 9 -3 3
3 4
3 5
3 6
3 7 -3 9
4 0
I nf or me d c o nse nt a n d de m o gra p h y
x
O ut patie nt visit (after ≥1 0 h fast)
x
Me dical hist or y
x
Eli gi bilit y criteria
x
x
P h ysical e xa m c ( hei g ht at Scree n 
o nl y)
x
Re vie w c o ntrace pti o n use -
W O C B P O nl y ( Secti o n 5. 3. 4 )
x 
x
Re vie w dr u g, alc o h ol/t o bacc o use
x
x
C O VI D -1 9 pre -scree ni n gd
x
S A R S -C o V -2 testi n g d
x
Te m perat ure c hec k d
x
C -S S R S a n d P H Q -9
x
x
x
x
x
Re vie w pri or or c o nc o mita nt 
treat me nts 
x 
x
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

A E m o nit ori n g
x 
x
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

I n patie nt sta y at C R U
x
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

Sta n dar dize d meals/s nac ks e
x
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

B o d y wei g ht 
x
Ta ble 3
Ta ble 4
x
x
x
x
Ta ble 3
Ta ble 4
S u pi ne 1 2 -lea d E C G
x
Ta ble 5
Si n gle, s u pi ne vital si g ns 
assess me nt f
x
Mi daz ola m a d mi nistrati o n
O m e praz ole a d mi nistrati o n
O C a d mi nistrati o n
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n g
x 
x 
x 
x 
x 
x 
x
x
x
x 
x 
x
Bl o o d S a m pli n g f or: h
- C he mistr y
x 
x
x
x
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7
T a ble 1 .
C o h ort 1 - O ver all Sc he d ule of Acti vities Scree ni n g t o Peri o d 5
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble 
ma y be f o u n d i n A p pe n di x 9
Scree ni n g
Peri o d 1
(M D Z + 
O M P o nl y)
Peri o d 2
(O C o nl y )
Peri o d 3 
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 4 
( P F- 0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 5 
(P F -0 7 0 8 1 5 3 2 +
O C )
D a y i n St u d y Peri o d a
-2 8 t o - 2
- 1
1
1
2- 4
5
1
2- 7
8
9- 1 4
1 5
1 6 - 2 1
2 2
2 3 -2 7
2 8
1
1
2- 4
5
D a ys i n St u d y b
-2 8 t o - 2
- 1
1
2
3- 5
6
7
8- 1 3
1 4
1 5- 2 0
2 1
2 2 - 2 7
2 8
2 9 -3 3
3 4
3 5
3 6
3 7 -3 9
4 0
- Calcit o ni n, a m ylase, li pase
x 
x
x
x
- Free T 4, T S H, li pi d pa nel , t otal 
bile aci ds
x 
x
- He mat ol o g y / H b A 1c
x 
x
x
- F S H ,i HI V, H Bs A g, H C V A b, 
H C V R N A, C -pe pti de
x
- Ser u m pre g na nc y test i
x 
x
- M D Z a n d 1 -h y dr o x y -M D Z P K
x j
x j
- O M P & 5 -h y dr o x y -O M P P K
x j
x j
- O C ( L E a n d E E) P K
x k
x k
x k
x k
x k
- P F -0 7 0 8 1 5 3 2 P K
x l
x
- 4-h y dr o x yc h olester ol , 
c h olester ol, 
Uri ne S a m pli n g f or:
- Uri ne dr u g testn
x 
x
- Uri nal ysis (a n d micr osc o p y, as
a p pr o priate)
x
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8
T a ble 1 .
C o h ort 1 - O ver all Sc he d ule of Acti vities Scree ni n g t o Peri o d 5
Visit I de ntifier
A b bre viati o ns use d i n t his ta ble 
ma y be f o u n d i n A p pe n di x 9
Scree ni n g
Peri o d 1
(M D Z + 
O M P o nl y)
Peri o d 2
(O C o nl y )
Peri o d 3 
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 4 
( P F- 0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 5 
(P F -0 7 0 8 1 5 3 2 +
O C )
D a y i n St u d y Peri o d a
-2 8 t o - 2
- 1
1
1
2- 4
5
1
2- 7
8
9- 1 4
1 5
1 6 - 2 1
2 2
2 3 -2 7
2 8
1
1
2- 4
5
D a ys i n St u d y b
-2 8 t o - 2
- 1
1
2
3- 5
6
7
8- 1 3
1 4
1 5- 2 0
2 1
2 2 - 2 7
2 8
2 9 -3 3
3 4
3 5
3 6
3 7 -3 9
4 0
a.
D a y  relati ve t o start of d osi n g Da y 1 of t hat Peri o d.
b.
D a y  relati ve t o first d ose of i n vesti gati o nal pr o d uct ( mi daz ola m/ o me praz ole) o n Da y 1 of Peri o d 1.
c.
C o m plete p h ysical e xa m at Scre e ni n g; ot her wise, brief e xa m if fi n di n gs d uri n g pre vi o us e xa m or ne w/ o pe n A Es, if a p pr o priate, at i n vesti gat or discreti o n. 
d.
Partici pa nts will be teste d f or S A R S -C O VI D -1 9 i nfecti o n b y P C R.  Test m ust be ne gati ve pri or t o a d missi o n o n Da y -1, Peri o d 1.  A s u bse q ue nt test will be 
d o ne acc or di n g t o l ocal pr oce d ure if partici pa nts de vel o p C O VI D -1 9 li ke s y m pt o ms.  Pri or t o S A R S -C o V -2 test, te m perat ure c hec k a n d C O VI D -1 9 pre -
scree ni n g f or C O VI D-1 9 relate d si g ns a n d s y m pt o ms will be d o ne. See als o Secti o n 8. 3. 5 ( C O VI D-1 9 S pecific Assess me nts). If partici pa nts test p ositi ve f or 
S A R S -C o V -2 i nfecti o n, t he y will be disc har ge d fr o m t he st u d y.
e.
M eals t o be pr o vi de d at a p pr o xi matel y 0 h, 4 h, a n d 1 0 h p ost A M d ose; pl us, s nac ks pr o vi de d acc or di n g t o Secti o n 5. 3. 1 .
f.
I ncl u des B P a n d P R pre d ose.
g.
D osi n g t o occ ur Q D wit h brea kfast as s pecifie d i n Secti o n 5. 3. 1 .
h.
C ollecti o n f o ll o wi n g fasti n g d urati o n s pecifie d i n Secti o n 5. 3. 1 .
i.
F S H f or fe male partici pa nts t o c o nfir m P M stat us o nl y.  Ser u m -h C G f or all W O C B P; test res ult s h o ul d c o nfir m n o pre g na nc y pri or t o d osi n g.
j.
F oll o w i n g mi daz ola m a n d o me praz ole d osi n g o n Da y 1 i n b ot h Peri o ds 1 a n d 4, mi daz ola m, o me praz ole, 1-O H -mi daz ola m, a n d 5 -h y dr o x y o me praz ole P K 
s h o ul d be o btai ne d at a p pr o xi matel y 2 4h p ost mi daz ola m a n d o me praz ole d ose. 
k.
F oll o w i n g O C d osi n g o n Da y 1 i n b ot h Peri o ds 2 a n d 5, L E a n d E E P K s h o ul d be o btai ne d at 2 4 h, 4 8 h, 7 2 h, 9 6 h a n d 1 2 0 h p ost O C d ose o n Da y 1 of t he 
sa me peri o d.
l.
T he P F -0 7 0 8 1 5 3 2 P K sa m ple s h o ul d be o btai ne d at 2 4 h o urs f oll o wi n g t he d ose i n P 3 D 2 8, w hic h is t he sa me as t he 0 h o ur P K sa m ple i n P 4 D 1 .
 
n.
Partici pa nts 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9
T a ble 2 .
C o h ort 1 - O ver all Sc he d ule of Acti vities Peri o d 6 t o E T
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 9
Peri o d 6
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 7
( P F-
0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 8
(P F -0 7 0 8 1 5 3 2 +
O C )
Peri o d 9 
( M D Z o nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele p h o ne
E T
D a y i n St u d y Peri o d a
1- 7
8- 1 4
1 5 -2 1 2 2 -2 8 2 9 -3 5 3 6 -4 2 4 3 -4 9 5 0 -5 6 5 7 -6 3
1
1
2- 5
6
- 1
1
2
7- 1 0
2 8 -3 5
-
D a ys i n St u d y b
4 1 -
4 7
4 8 -5 4 5 5 -6 1 6 2 -6 8 6 9 -7 5 7 6 -8 2 8 3 -8 9 9 0 -9 6 9 7 - 1 0 3
1 0 4
1 0 5
1 0 6 -
1 0 9
1 1 0
1 2 4
1 2 5
1 2 6
1 3 2-
1 3 5
1 5 3 - 1 6 0
-
I nf or me d c o nse nt an d de m o gra p h y
O ut patie nt visit (after ≥1 0 -h fast)
x
Me dical hist or y
x
Eli gi bilit y criteria
P h ysical e xa m ( hei g ht at Scree n o nl y)
X c
Re vie w c o ntrace pti o n use - W O C B P 
O nl y (Secti o n 5. 3. 4 )
x
x 
x
Re vie w dr u g, alc o h ol/t o bacc o use
x


x
C O VI D -1 9 pre -scree ni n gd
x
S A R S -C o V -2 testi n gd
x
Te m perat ure c hec k d
x
C -S S R S a n d P H Q -9 e
x
x
x
x
x
x
x
Re vie w pri or or c o nc o mita nt treat me nts
 
 
 
 
 
 
 
 
 
 
 

x 
x


x 
x
A E m o nit ori n g
 
 
 
 
 
 
 
 
 
 
 

x 
x


x 
x
I n patie nt sta y at Cli nical Researc h U nit
 
 
 
 
 
 
 
 
 
 
 

x f
x g

x f
Sta n dar dize d meals/s nac ks h
 
 
 
 
 
 
 
 
 
 
 
 

x


B o d y wei g ht i
x
x
x
x
x
x
x
x
x
Ta ble 5
Ta ble 3
Ta ble 4
x
Ta ble 3
x
x
S u pi ne 1 2 -lea d E C G
x
x
x
Si n gle, s u pi ne vital si g ns assess me nt j
x
x
x
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n k
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
O m e praz ole a d mi nistrati o n
Mi daz ola m a d mi nistrati o n
O C a d mi nistrati o n
Bl o o d S a m pli n g f or: l
- C he mistr ym
x 
x
x 
x 
x
x
x 
x
x
- Calcit o ni n, a m ylase, li pase m
x 
x
x 
x 
x
x
x 
x
x
- Free T 4, T S H, li pi d pa nel , t otal bile 
aci ds
x
x
x
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0
T a ble 2.
C o h ort 1 - O ver all Sc he d ule of Acti vities Peri o d 6 t o E T
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 9
Peri o d 6
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 7
( P F-
0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 8
(P F -0 7 0 8 1 5 3 2 +
O C )
Peri o d 9 
( M D Z o nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele p h o ne
E T
D a y i n St u d y Peri o d a
1- 7
8- 1 4
1 5 -2 1 2 2 -2 8 2 9 -3 5 3 6 -4 2 4 3 -4 9 5 0 -5 6 5 7 -6 3
1
1
2- 5
6
- 1
1
2
7- 1 0
2 8 -3 5
-
D a ys i n St u d y b
4 1 -
4 7
4 8 -5 4 5 5 -6 1 6 2 -6 8 6 9 -7 5 7 6 -8 2 8 3 -8 9 9 0 -9 6 9 7 - 1 0 3
1 0 4
1 0 5
1 0 6 -
1 0 9
1 1 0
1 2 4
1 2 5
1 2 6
1 3 2-
1 3 5
1 5 3 - 1 6 0
-
- He mat ol o g y / H b A 1cn
x
x
x
x 
x
x
- F S H, o HI V, H Bs A g, H C V R N A, 
H C V A b, C -pe pti de 
- Ser u m pre g na nc y test o
x
- O M P a n d 5 -h y dr o x y -O M P P K
x p
x
-
MD Z a n d 1- h y dr o x y -M D Z
P K
x p
x p
x
- O C ( L E/ E E) P K
x q
x q
x q
x
- P F -0 7 0 8 1 5 3 2 P K
x r
x
x
- 4 -β -h y dr o x yc h olester ol , c h olester ol, 
Uri ne S a m pli n g f or:
- Uri ne dr u g test s
- Uri nal ysis (a n d micr osc o p y, as 
a p pr o priate)
x
x
a.
D a y  relati ve t o start of d osi n g Da y 1 of t hat Peri o d.
b.
D a y  relati ve t o first d ose of i n vesti gati o nal pr o d uct ( mi daz ola m/ o me praz ole) o n Da y 1 of Peri o d 1.
c.
Brief e xa m if fi n di n gs d uri n g pre vi o us e xa m or ne w/ o pe n A Es, if a p pr o priate, at i n vesti gat or discreti o n.
d.
Partici pa nts will be teste d f or S A R S -C O VI D -1 9 i nfecti o n b y P C R.  Test m ust be ne gati ve pri or t o rea d missi o n o n Da y -1, Peri o d 9.  A s u bse q ue nt test w ill 
be d o ne acc or di n g t o l ocal pr oce d ure if partici pa nts de vel o p C O VI D -1 9 li ke s y m pt o ms.  Pri or t o S A R S -C o V -2 test, te m perat ure c hec k a n d C O VI D -1 9 
pre -scree ni n g f or C O VI D-1 9 relate d si g ns a n d s y m pt o ms will be d o ne. See als o Secti o n 8. 3. 5 ( C O VI D-1 9 S pecific Assess me nts). If partici pa nts test p ositi ve 
f or S A R S-C o V -2 i nfecti o n, t he y will be disc har ge d fr o m t he st u d y.
e.
C- S S R S a n d P H Q will be a d mi nistere d i n Peri o d 6 o n Da ys 1 4, 2 8, 4 2, 5 6, a n d 6 3.
f.
Disc har ge fr o m C R U.
g.
Rea d mit t o C R U.
h.
Meals t o be pr o vi de d at a p pr o xi matel y 0 h , 4h , a n d 1 0h p ost A M d ose.
i.
B o d y  wei g ht t o be o btai ne d o nce wee kl y i n Peri o d 6 o n Da ys 1, 8, 1 5, 2 2, 2 9, 3 6, 4 3, 5 0, a n d 5 7.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1
T a ble 2 .
C o h ort 1 - O ver all Sc he d ule of Acti vities Peri o d 6 t o E T
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 9
Peri o d 6
(P F -0 7 0 8 1 5 3 2 o nl y)
Peri o d 7
( P F-
0 7 0 8 1 5 3 2 
+ M D Z + 
O M P)
Peri o d 8
(P F -0 7 0 8 1 5 3 2 +
O C )
Peri o d 9 
( M D Z o nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele p h o ne
E T
D a y i n St u d y Peri o d a
1- 7
8- 1 4
1 5 -2 1 2 2 -2 8 2 9 -3 5 3 6 -4 2 4 3 -4 9 5 0 -5 6 5 7 -6 3
1
1
2- 5
6
- 1
1
2
7- 1 0
2 8 -3 5
-
D a ys i n St u d y b
4 1 -
4 7
4 8 -5 4 5 5 -6 1 6 2 -6 8 6 9 -7 5 7 6 -8 2 8 3 -8 9 9 0 -9 6 9 7 - 1 0 3
1 0 4
1 0 5
1 0 6 -
1 0 9
1 1 0
1 2 4
1 2 5
1 2 6
1 3 2-
1 3 5
1 5 3 - 1 6 0
-
j.
I ncl u des B P a n d P R pred ose.
k.
D osi n g t o occ ur Q D wit h brea kfast.  N ote t hat t here is n o P F -0 7 0 8 1 5 3 2 a d mi nistrati o n o n Da y 1 1 0 or a n yti me t hereafter.
l.
C ollecti o n f oll o wi n g fasti n g d urati o n s pecifie d i n. Secti o n 5. 3. 1 . 
m.
T o be o btai ne d o n Da ys 1, 1 5, 2 9, 4 3, a n d 5 7 i n Peri o d 6.
n.
T o be o btai ne d o n Da ys 1 5 a n d 4 3 i n Peri o d 6.
o.
F S H f or fe male partici pa nts t o c o nfir m P M stat us o nl y.  Ser u m -h C G f or all W O C B P; test res ult s h o ul d c o nfir m n o pre g na nc y pri or t o d osi n g.
p.
F oll o w i n g mi daz ola m a n d o me praz ole d osi n g o n Da y 1 i n Peri o d 7, mi daz ola m, o me praz ole, 1-O H -mi daz ola m, a n d 5 -h y dr o x y o me praz ole P K s h o ul d be 
o btai ne d at a p pr o xi matel y 2 4 h p ost mi daz ola m a n d o me praz ole d oses.   F oll o w i n g t he mi daz ola m d ose o n Da y 1 i n Peri o d 9, mi daz ola m a n d 
1- O H -mi daz ola m P K s h o ul d be o btai ne d at a p pr o xi matel y 2 4 h p ost -d ose.
q.
F oll o w i n g O C d osi n g i n Peri o d 5, L E a n d E E P K s h o ul d be o btai ne d at 1 2 0h p ost d ose o n Da y 1 of t he sa me pe ri o d.  F oll o wi n g O C d osi n g i n Peri o d 8, L E 
a n d E E P K s h o ul d be o btai ne d at 2 4 h , 4 8h , 7 2h, 9 6 h , a n d 1 2 0h p ost O C d ose o n Da y 1 of t he sa me peri o d. 
r.
T he P F -0 7 0 8 1 5 3 2 P K sa m ple s h o ul d be o btai ne d at 2 4 h o urs f oll o wi n g t he d ose i n  P 6 D 6 3 , w hic h is t he sa me as t he 0 hr P K sa m ple i n P 7 D 1 .
s.
Partici pa nts 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 2
T a ble 3.
Sc he d ule of Acti vities – D a y 1 of Peri o d 1 ( Mi d az ol a m + O me pr az ole O N L Y), Peri o d 4 ( Mi d az ol a m + O me pr az ole 
+ P F -0 7 0 8 1 5 3 2 8 0 m g Q D), Peri o d 7 ( Mi d az ol a m + O me pr az ole + P F- 0 7 0 8 1 5 3 2 2 6 0 m g Q D), a n d Peri o d 9 
( Mi d az ol a m O N L Y)
H o urs Rel ati ve t o D osi n g at 0 h
0
0. 5
1
2
3
4
6
8
1 0
1 4
B o d y Wei g ht
X
Mi daz ola m ad mi nistrati o n
X a
O m e praz ole a d mi nistrati o n ( Peri o ds 1, 4, a n d 7 o nly)
X a
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n ( Peri o ds 4 a n d 7 o nly)
X a
Bl o o d s a m pli n g f or: b
- C he mistr y ( Peri o d 9 o nly)
x
- Calcit o ni n, a m ylase, li pase ( Peri o d 9 o nly)
x
- Free T 4, T S H, li pi d pa nel , t otal bile aci ds ( Peri o d 9 o nly)
x
- He mat ol o g y / H b A 1c ( Peri o d 9 o nly)
x
- Mi daz ola m a n d 1 -h y dr o x y -M D Z P K
x
x
x
x
x
x
x
x
x
x
- O me praz ole a n d 5 -h y dr o x y -O M P P K ( Peri o ds 1, 4, a n d 7 o nly)
x
x
x
x
x
x
x
x
x
x
- 4 -β -h y dr o x yc h olester ol/c h olester ol, 
x
- P F -0 7 0 8 1 5 3 2 P K ( Peri o ds 4 a n d 7 o nly)d
x
Uri ne s a m pli n g f or:
- Uri nal ysis a n d micr osc o p y, as a p pr o priate (Peri o d 1 o nly )
x
a.
D osi n g t o occ ur wit h brea kfast as s pecifie d i n Secti o n 5. 3. 1 . 
b.
C ollecti o n f oll o wi n g fasti n g d urati o n acc or di n g t o d osi n g fre q ue nc y as s pecifie d i n Secti o n 5. 3. 1 .
d.
F or Peri o ds 4 a n d 7 o nl y, P F -0 7 0 8 1 5 3 2 P K sa m ple t o be dra w n at 0 h , a p pr o xi matel y 2 4h after t he P F -0 7 0 8 1 5 3 2 m or ni n g d ose o n t he pre vi o us da y 
( Peri o d 3 Da y 2 8 a n d Peri o d 6 Da y 6 3, res pecti vel y).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 3
T a ble 4 .
Sc he d ule of Acti vities – D a y 1 of Peri o d 2 ( O C O N L Y), Peri o d 5 ( O C + P F- 0 7 0 8 1 5 3 2 8 0 m g Q D) a n d Peri o d 8 ( O C 
+ P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D)
H o urs Rel ati ve t o D osi n g at 0 h
0
0. 7 5
2
4
8
1 2
O C a d mi nistrati o n
X a
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n ( Peri o ds 5 a n d 8 o nly)
X a
Bl o o d s a m pli n g f or :b
- O C P K
x
x
x
x
x
x
- Mi daz ola m, 1 -h y dr o x y -M D Z, o me praz ole, 5 -h y dr o x y -O M P P K
X c
- P F -0 7 0 8 1 5 3 2 P K ( Peri o ds 5 a n d 8 o nly)
x
a.
D osi n g t o occ ur wit h brea kfast as s pecifie d i n Secti o n 5. 3. 1 . 
b.
C ollecti o n f oll o wi n g fasti n g d urati o n acc or di n g t o d osi n g fre q ue nc y as s pecifie d i n Secti o n 5. 3. 1 .
c.
M i daz ola m, 1-h y dr o x y -M D Z, o me praz ole, a n d 5 -h y dr o x y -O M P P K sa m ples t o be dra w n at 0 h , a p pr o xi matel y 2 4h after t he mi daz ola m/ o me praz ole m or ni n g 
d ose o n t he pre vi o us da y ( Da y 1 of Peri o d 1, Peri o d 4 , a n d Peri o d 7 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 4
T a ble 5 .
Sc he d ule of Acti vities – D a y 2 8 of Peri o d 3 a n d D a y 6 3 of Peri o d 6 ( P F- 0 7 0 8 1 5 3 2 o nl y)
H o urs Rel ati ve t o D osi n g at 0 h
0
0. 5
1
2
4
6
8
1 0
1 4
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n 
X a
Bl o o d s a m pli n g f or: b
- P F -0 7 0 8 1 5 3 2 P K
x
x
x
x
x
x
x
x
x
Uri ne sa m pli n g f or:
- Uri nal ysis a n d micr osc o p y, as a p pr o priate 
x
a.
D osi n g t o occ ur wit h brea kfast as s pecifie d i n Secti o n 5. 3. 1 . 
b.
C ollecti o n f oll o wi n g fasti n g d urati o n acc or di n g t o d osi n g fre q ue nc y as s pecifie d i n Secti o n 5. 3. 1 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 5
T a ble 6 .
C o h ort 2: Sc he d ule of Acti vities
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 9
Scree ni n g Peri o d 1
(M D Z
o nl y)
Peri o d 2 ( O ut -p atie nt : Se ma gl uti de o nl y )
Peri o d 3 
( Se m a gl uti de
+ M D Z)
Peri o d 4 
( MD Z O nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele -
p h o ne
E T
D a y i n St u d y 
Peri o d a
-2 8 t o - 2 - 1
1
1-
7
8-
1 4
1 5 -
2 1
2 2 -
2 8
2 9 -
3 5
3 6 -
4 2
4 3 -
4 9
5 0 -
5 6
5 7 -
6 3
6 4 -
7 0
7 1 -
7 7
7 8 -
8 4
8 5 -
9 1
9 2 -
9 8
9 9 -
1 0 5
1 0 6 -
1 1 2
1 1 3-
1 1 9
1 2 0 -
1 2 6
1 2 7 -
1 3 3
1 3 4 -
1 4 0
1 4 1 -
1 4 6
1 4
7
1
2
- 1
1
2
7- 1 0 2 8 -3 5
Wee k i n St u d y 
Peri o d a
-
-
-
1
2
3
4
5
6
7
8
9
1 0 1 1
1 2 1 3 1 4 1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 1
-
-
-
-
-
-
-
-
D a ys i n St u d y b
-2 8 t o - 2 - 1
1
2-
8
9-
1 5
1 6 -
2 2
2 3 -
2 9
3 0 -
3 6
3 7 -
4 3
4 4 -
5 0
5 1 -
5 7
5 8 -
6 4
6 5 -
7 1
7 2 -
7 8
7 9 -
8 5
8 6 -
9 2
9 3 -
9 9
1 0 0-
1 0 6
1 0 7 -
1 1 3
1 1 4-
1 2 0
1 2 1 -
1 2 7
1 2 8 -
1 3 4
1 3 5 -
1 4 1
1 4 2 -
1 4 7
1 4
8
1 4 9
1 5 0 1 6 4
1 6 5
1 6 6 1 7 2-
1 7 5
1 9 3 -
2 0 0
I nf or me d c o nse nt  
a n d de m o gra p h y
x
O ut patie nt visit 
(after ≥1 0 h fast)
x
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Me dical hist or y
x
x
x
Eli gi bilit y criteria
x 
x
P h ysical e xa m c
( hei g ht at Scree n 
o nl y)
x
x
Re vie w 
c o ntrace pti o n use 
(Secti o n 5. 3. 4 )d
x
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
x
x
x 
x 
x
C O VI D - 1 9 
pre -scree ni n ge
x
x
x
S A R S -C o V -2 
testi n ge
x
x
x
x
Te m perat ure c hec k e
x
x
x
x
C- S S R S a n d P H Q - 9f
x 
x
x
x
x
x
x
x
Re vie w dr u g, 
alc o h ol/t o bacc o use g
x 
x 
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
x
x
 

Re vie w pri or or 
c o nc o mita nt 
treat me ntsg
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
x
 

x
 

x 
x 
x
A E m o nit ori n g g
x 
x 
x 
x
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
x
 

x
 

x 
x 
x
I n patie nt sta y at 
C R U
x 
x
x h
x i
x 
x h x i

x h 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 6
T a ble 6 .
C o h ort 2: Sc he d ule of Acti vities
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 9
Scree ni n g Peri o d 1
(M D Z
o nl y)
Peri o d 2 ( O ut -p atie nt : Se ma gl uti de o nl y )
Peri o d 3 
( Se m a gl uti de
+ M D Z)
Peri o d 4 
( MD Z O nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele -
p h o ne
E T
D a y i n St u d y 
Peri o d a
-2 8 t o - 2 - 1
1
1-
7
8-
1 4
1 5 -
2 1
2 2 -
2 8
2 9 -
3 5
3 6 -
4 2
4 3 -
4 9
5 0 -
5 6
5 7 -
6 3
6 4 -
7 0
7 1 -
7 7
7 8 -
8 4
8 5 -
9 1
9 2 -
9 8
9 9 -
1 0 5
1 0 6 -
1 1 2
1 1 3-
1 1 9
1 2 0 -
1 2 6
1 2 7 -
1 3 3
1 3 4 -
1 4 0
1 4 1 -
1 4 6
1 4
7
1
2
- 1
1
2
7- 1 0 2 8 -3 5
Wee k i n St u d y 
Peri o d a
-
-
-
1
2
3
4
5
6
7
8
9
1 0 1 1
1 2 1 3 1 4 1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 1
-
-
-
-
-
-
-
-
D a ys i n St u d y b
-2 8 t o - 2 - 1
1
2-
8
9-
1 5
1 6 -
2 2
2 3 -
2 9
3 0 -
3 6
3 7 -
4 3
4 4 -
5 0
5 1 -
5 7
5 8 -
6 4
6 5 -
7 1
7 2 -
7 8
7 9 -
8 5
8 6 -
9 2
9 3 -
9 9
1 0 0-
1 0 6
1 0 7 -
1 1 3
1 1 4-
1 2 0
1 2 1 -
1 2 7
1 2 8 -
1 3 4
1 3 5 -
1 4 1
1 4 2 -
1 4 7
1 4
8
1 4 9
1 5 0 1 6 4
1 6 5
1 6 6 1 7 2-
1 7 5
1 9 3 -
2 0 0
Sta n dar dize d 
meals/s nac ks j
x

x
 

 
 

B o d y wei g ht k
x
Ta ble 7
x
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Ta ble 7
x
Ta ble 7
x 
x
S u pi ne 1 2 -lea d E C G
x
x
x
x
Si n gle, s u pi ne vital 
si g ns assess me ntl
x
x
x
x
Se ma gl uti de d osi n g m
x
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Mi daz ola m
d osi n g
Bl o o d S a m pli n g 
f or:n
- C he mistr yo
x
x
x
x
x
x
x
x 
x 
x
- Calcit o ni n, 
a m ylase, li pase o
x
x
x
x
x
x
x
x 
x
-
He mat ol o g y / H b A 1co
x
x
x
x
x
x
x
x 
x 
x
- Free T 4, T S H, li pi d 
pa nel, t otal bile 
aci ds
x
x
x 
x
- F S H p, HI V, 
H Bs A g, H C V A b, 
H C V R N A, C-
pe pti de
x
- Ser u m pre g na nc y 
testp
x 
x
x
x
x 
x
- Uri ne pre g na nc y 
testg
x 
x 
x 
x 
x 
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
x
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 7
T a ble 6 .
C o h ort 2: Sc he d ule of Acti vities
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 9
Scree ni n g Peri o d 1
(M D Z
o nl y)
Peri o d 2 ( O ut -p atie nt : Se ma gl uti de o nl y )
Peri o d 3 
( Se m a gl uti de
+ M D Z)
Peri o d 4 
( MD Z O nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele -
p h o ne
E T
D a y i n St u d y 
Peri o d a
-2 8 t o - 2 - 1
1
1-
7
8-
1 4
1 5 -
2 1
2 2 -
2 8
2 9 -
3 5
3 6 -
4 2
4 3 -
4 9
5 0 -
5 6
5 7 -
6 3
6 4 -
7 0
7 1 -
7 7
7 8 -
8 4
8 5 -
9 1
9 2 -
9 8
9 9 -
1 0 5
1 0 6 -
1 1 2
1 1 3-
1 1 9
1 2 0 -
1 2 6
1 2 7 -
1 3 3
1 3 4 -
1 4 0
1 4 1 -
1 4 6
1 4
7
1
2
- 1
1
2
7- 1 0 2 8 -3 5
Wee k i n St u d y 
Peri o d a
-
-
-
1
2
3
4
5
6
7
8
9
1 0 1 1
1 2 1 3 1 4 1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 1
-
-
-
-
-
-
-
-
D a ys i n St u d y b
-2 8 t o - 2 - 1
1
2-
8
9-
1 5
1 6 -
2 2
2 3 -
2 9
3 0 -
3 6
3 7 -
4 3
4 4 -
5 0
5 1 -
5 7
5 8 -
6 4
6 5 -
7 1
7 2 -
7 8
7 9 -
8 5
8 6 -
9 2
9 3 -
9 9
1 0 0-
1 0 6
1 0 7 -
1 1 3
1 1 4-
1 2 0
1 2 1 -
1 2 7
1 2 8 -
1 3 4
1 3 5 -
1 4 1
1 4 2 -
1 4 7
1 4
8
1 4 9
1 5 0 1 6 4
1 6 5
1 6 6 1 7 2-
1 7 5
1 9 3 -
2 0 0
- M D Z, 1 -h y dr o x y -
M D Z P K
x q
x q
x q
x
- Se ma gl uti de P K r
x
x
x
x
x
- 4- β-
h y dr o x yc h olester ol , 
c h olester ol, 
Uri ne S a m pli n g 
f or:
- Uri ne dr u g test t
x 
x
x
x
- Uri nal ysis (a n d 
micr osc o p y, as 
a p pr o priate)
x
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 8
T a ble 6 .
C o h ort 2: Sc he d ule of Acti vities
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 9
Scree ni n g Peri o d 1
(M D Z
o nl y)
Peri o d 2 ( O ut -p atie nt : Se ma gl uti de o nl y )
Peri o d 3 
( Se m a gl uti de
+ M D Z)
Peri o d 4 
( MD Z O nl y)
F/ U
Visit
F/ U 
C o nt act 
Tele -
p h o ne
E T
D a y i n St u d y 
Peri o d a
-2 8 t o - 2 - 1
1
1-
7
8-
1 4
1 5 -
2 1
2 2 -
2 8
2 9 -
3 5
3 6 -
4 2
4 3 -
4 9
5 0 -
5 6
5 7 -
6 3
6 4 -
7 0
7 1 -
7 7
7 8 -
8 4
8 5 -
9 1
9 2 -
9 8
9 9 -
1 0 5
1 0 6 -
1 1 2
1 1 3-
1 1 9
1 2 0 -
1 2 6
1 2 7 -
1 3 3
1 3 4 -
1 4 0
1 4 1 -
1 4 6
1 4
7
1
2
- 1
1
2
7- 1 0 2 8 -3 5
Wee k i n St u d y 
Peri o d a
-
-
-
1
2
3
4
5
6
7
8
9
1 0 1 1
1 2 1 3 1 4 1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 1
-
-
-
-
-
-
-
-
D a ys i n St u d y b
-2 8 t o - 2 - 1
1
2-
8
9-
1 5
1 6 -
2 2
2 3 -
2 9
3 0 -
3 6
3 7 -
4 3
4 4 -
5 0
5 1 -
5 7
5 8 -
6 4
6 5 -
7 1
7 2 -
7 8
7 9 -
8 5
8 6 -
9 2
9 3 -
9 9
1 0 0-
1 0 6
1 0 7 -
1 1 3
1 1 4-
1 2 0
1 2 1 -
1 2 7
1 2 8 -
1 3 4
1 3 5 -
1 4 1
1 4 2 -
1 4 7
1 4
8
1 4 9
1 5 0 1 6 4
1 6 5
1 6 6 1 7 2-
1 7 5
1 9 3 -
2 0 0
a.
D a y  or Wee k relati ve t o start of d osi n g Da y 1 of t hat Peri o d.
b.
D a y  relati ve t o first d ose of mi daz ola m o n Da y 1 of Peri o d 1. 
c.
C o m plete p h ysical e xa m at Scree ni n g, ot her wise, brief e xa m if fi n di n gs d uri n g pre vi o us e xa m or ne w/ o pe n A Es, if a p pr o priate, at i n vesti gat or discreti o n.
d.
F or W O C B P, c o ntrace pti ve use w ill be re viewe d a n d a uri ne pre g na nc y test c o n d ucte d at wee kl y o u t-patie nt visits.  If t he uri ne pre g na nc y test is p ositi ve or 
i nc o ncl usi ve, a ser u m pre g na nc y test will be c o n d ucte d.
e.
Partici pa nts will be teste d f or S A R S -C O VI D -1 9 i nfecti o n b y P C R pri or t o a d missi o n o n Da y -1 i n Peri o ds 1, 3 a n d 4.  A s u bse q ue nt test will be d o ne 
acc or di n g t o l ocal pr oce d ure if partici pa nts de vel o p C O VI D -1 9 li ke s y m pt o ms or si g ns.  Pri or t o S A R S -C o V -2 test, a te m perat ure c hec k a n d C O VI D -1 9 
pre -scree ni n g f or C O VI D-1 9 relate d si g ns a n d s y m pt o ms will be d o ne.  See als o Secti o n 8. 3. 5 ( C O VI D-1 9 S pecific Assess me nts ). If partici pa nts test 
p ositi ve f or S A R S -C o V -2 i nfecti o n, t he y will be disc har ge d fr o m t he st u d y.
f. 
C-S S R S a n d P H Q - 9 will be a d mi nistere d i n Peri o d 2 at t he Wee k 5, 9, 1 3, a n d 1 7 visits.
g.
T o be m o nit ore d at wee kl y o ut-patie nt visits i n Peri o d 2.
h.
Disc har ge fr o m C R U o n Da y 1 i n Peri o d 2 a n d o n Da ys 2 i n Peri o ds 3 a n d 4 .
i.
Rea d mit t o C R U.
j.
Meals t o be pr o vi de d at a p pr o xi matel y 0 h , 4h , a n d 1 0h p ost A M d ose.
k.
B o d y  wei g ht t o be o btai ne d o nce wee kl y i n Peri o d 2 w he n partici pa nts ret ur n t o t he C R U f or t heir wee kl y se ma gl uti de i njecti o n s.
l.
I ncl u des B P a n d P R.
m.
D osi n g t o occ ur w ee kl y, prefera bl y i n t he m or ni n g, as s pecifie d i n Secti o n 5. 3. 1 .
n.
C ollecti o n f oll o wi n g fasti n g d urati o n s pecifie d i n Secti o n 5. 3. 1 .
o.
T o be c ollecte d o n Da ys 2 2 , 50 , 7 8 , a n d 10 6 , a n d 13 4 of Peri o d 2.
p .
F S H f or f e male partici pa nts t o c o nfir m P M stat us o nl y.  Ser u m b- h C G f or all W O C B P; test res ult s h o ul d c o nfir m n o pre g na nc y pri or t o d osi n g.
q.
F oll o w i n g mi daz ola m d osi n g o n Da y 1 i n Peri o ds 1, 3, a n d 4, mi daz ola m a n d 1 -h y dr o x y mi daz ola m P K s h o ul d be o btai ne d at a p pr o xi matel y 2 4 h p ost d ose.
r.
Se m a gl uti de P K sa m ples t o be c ollecte d pri or t o t he first 0. 5, 1. 0, 1. 7, a n d 2. 4 m g se ma gl uti de d ose s at t he i n-patie nt visits at Wee ks 5, 9, 1 3, a n d 1 7, 
res pecti vel y, d uri n g Peri o d 2, a n d pri or t o d osi n g i n Peri o d 3, Da y 1.  
t.
Partici pa nts 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 v esti gat or.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F - 07 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , 0 7 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 9
T a ble 7.
Sc he d ule of Acti vities – D a y 1 of Peri o d 1 ( Mi d az ol a m O N L Y), Peri o d 3 ( Mi d az ol a m + Se m a gl uti de 2. 4 m g), a n d 
Peri o d 4 ( Mi d az ol a m O N L Y)
H o urs Rel ati ve t o D osi n g at 0 h
0
0. 5
1
2
3
4
6
8
1 0
1 4
B o d y wei g ht
x
Mi daz ola m
a d mi nistrati o n
x a
S e ma gl uti de a d mi nistrati o n ( Peri o d 3 o nly)
x a
Bl o o d s a m pli n g f or: b
- C he mistr y 
x
- Calcit o ni n, a m ylase, li pase 
x
- Free T 4, T S H, li pi d pa nel , t otal bile aci ds
x
- He mat ol o g y / H b A 1c
x
- Mi daz ola m a n d 1 -h y dr o x y -M D Z
P K
x
x
x
x
x
x
x
x
x
x
- S e ma gl uti de P K ( Peri o d 3 o nly )
x
- 4 -β -h y dr o x yc h olester ol/c h olester ol, 
x
a.
D osi n g t o occ ur wit h brea kfast as s pecifie d i n Secti o n 5. 3. 1 . 
b.
C ollecti o n f oll o wi n g fasti n g d urati o n acc or di n g t o d osi n g fre q ue nc y as s pecifie d i n Secti o n 5. 3. 1 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 0
2. I N T R O D U C TI O N
G L P- 1 is a ne ur oe n d ocri ne h or m o ne t hat is pre d o mi na ntl y release d fr o m t he s mall i ntesti ne 
i n res p o nse t o f o o d i nta ke.1  G L P- 1 acti vati o n of t he G L P- 1 R sti m ulates i ns uli n release, 
i n hi bits gl uca g o n secreti o n i n a gl uc ose-de pe n de nt ma n ner, a n d dela y s gastric e m pt yi n g.2 ,3
I n a d diti o n, G LP- 1 has bee n s h o w n t o i ncrease satiet y  an d s u p press f o o d i nta ke. 4
P F -0 7 0 8 1 5 3 2 is a n orall y a d mi nistere d, p ote nt a n d selecti ve G L P -1 R a g o nist i n de vel o p me nt 
as a dj u nct t o diet a n d e xercise, t o i m pr o ve glyce mic c o ntr ol i n T 2 D M, a n d f or c hr o nic wei g ht 
ma na ge me nt i n a p o p ulati o n t hat is o ver wei g ht wit h c o - m or bi dities or w h o ha ve o besity.   
2. 1. St u d y R ati o n ale
T he p ur p ose of t his P hase 1, o pe n- la bel, fi xe d-se q ue nce st u dy is t o e val uate t he effect of 
2 d ose le vels of P F -0 7 0 8 1 5 3 2 a d mi nistere d t o stea d y state o n t he S D p har mac o ki netics of 
mi daz ola m , o me praz ole, a n d a n O C ( L E/ E E) (C o h ort 1 ), a n d t o e val uate t he effect of 
stea d y-state se ma gl uti de o n t he S D p har mac o ki netics of mi daz ola m ( C o h ort 2 ), i n ot her wise 
healt h y , o bese , a d ult fe male partici pa nt s. T he i nte nt of t his st u d y is t o ge nerate safety, 
t olera bilit y, a n d P K data f or f urt her cli nical de vel o p me nt .
2. 2. B ac k gr o u n d 
T 2 D M is esti mate d t o affect m ore t ha n 4 2 4 milli o n pe o ple w orl d wi de ,5 a n d t he pre vale nce of 
T 2 D M wit hi n t he U S is esti mate d t o ra n ge fr o m 1 2 t o 1 4 %.6 Patie nts wit h p o orl y  c o ntr olle d 
T 2 D M ha ve a n i ncrease d ris k of de vel o pi n g c o m plicati o ns ass ociate d wit h b ot h 
micr o vasc ular a n d macr o vasc ular disease, i ncl u di n g ne p hr o pat h y , ne ur o pat h y, reti n o pat hy, 
car di o vasc ular disease a n d str o ke; a n d are at 2 t o 4 ti mes i ncrease d ris k of m ortalit y t ha n 
a d ults w h o d o n ot ha ve dia betes. 7 W hile e xisti n g p har mac ol o gical o pti o ns f or t he tr eat me nt 
of dia betes ma y  pr o vi de satisfact or y glyc e mic c o ntr ol f or s o me patie nts, t here re mai ns a lar ge 
n u m ber of patie nts w h o d o n ot ac hie ve tar get gl yc ate d H b A 1c le vels, s u g gesti n g a nee d f or 
a d diti o nal t hera pe utic o pti o ns.
O besit y  is a c hr o nic disease t hat is ass ociate d wit h seri o us c o -m or bi dities, i ncl u di n g T 2 D M, 
d y sli pi de mia, h yperte nsi o n, at her oscler osis, o bstr ucti ve slee p a p nea a n d certai n ca ncers, 8 a n d 
is als o ass ociate d wit h i ncrease d all-ca use m ortalit y.9  T he gl o bal b ur de n of o besit y  is hi g h 
wit h m ore t ha n 6 0 0 milli o n a d ults esti mate d t o h a ve o besit y w orl d wi de.  I n a d diti o n, t he 
pre vale nce of o besit y  has d o u ble d i n m ore t ha n 7 0 c o u ntries si nce 1 9 8 0 a n d p oses a maj or 
p u blic healt h c halle n ge. 1 0 First li ne treat me nt f or o besit y is lifestyl e i nter ve nti o n i ncl u di n g 
diet, e xercise a n d be ha vi oral t hera p y.  W hile effecti ve i n ma n y patie nts, lifest yle i nter ve nti o n 
is ofte n n ot s ustai na ble, a n d ma n y patie nts re gai n wei g ht after i nitial wei g ht l oss.1 1
P har mac ot hera p y has bee n a p pr o ve d f or t he l o n g -ter m treat me nt of o besit y a n d ca n be a 
usef ul a dj u nct t o lifest yl e i nter ve nti o n t o a u g me nt a n d mai ntai n wei g ht l oss.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 1
Mar kete d i njecta ble G L P-1 R a g o nists ha ve de m o nstrate d r o b ust gl y ce mic efficac y, wei g ht 
l oss, a n d car di o vasc ular safety, wit h m ore t ha n o ne mar kete d a ge nt de m o nstrati n g 
car di o vasc ular be nefit. 1 2  Base d o n t he cli nical hist or y  of i njecta ble G L P- 1 R a g o nists, a n 
oral, s mall m olec ule G L P- 1 R a g o nist is e x pecte d t o i m pr o ve gl uc ose c o ntr ol a n d re d uce 
H b A 1c le vels i n patie nts wit h T 2 D M, w hile decreasi n g a p petite a n d b o d y wei g ht , res ulti n g i n 
wei g ht l oss i n patie nts wit h T 2 D M a n d o besit y , w hile a v oi di n g t he s u bc uta ne o us i njecti o n 
re q uire d by c urre ntl y a vaila ble pe pti dic G LP- 1 R a g o nists .
2. 2. 1. N o ncli nic al P h ar m ac ol o g y
Refer t o t he I B f or details o n t he n o ncli nical p har mac ol o g y of P F -0 7 0 8 1 5 3 2 .
2. 2. 2. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
I n rats a n d m o n ke ys f oll o wi n g si n gle I V a n d oral d osi n g, P F-0 7 0 8 1 5 3 2 e x hi bite d l o w C L p
(1 3 a n d 0. 6 m L / mi n/ k g, res pecti vely) , wit h l o w t o m o derate stea d y-state Vss ( 0. 7 6 a n d 
0. 2 1 L/ k g, res pecti vel y), lea di n g t o a t ½ of 1. 6 h o urs i n rats a n d 8. 8 h o urs i n m o n ke y s.
Re nal 
e xcreti o n was ne gli gi ble i n b ot h s pecies, a n d b iliar y e xcreti o n was mi ni mal i n rats. T he 
s yste mic e x p os ure (assesse d b y A U C a n d Cma x ) of PF- 0 7 0 8 1 5 3 2 f oll o wi n g oral re peat d ose 
pi v otal t o xicit y  st u dies i n rats, ra b bits a n d m o n ke ys ge nerally i ncrease d i n a d ose -
pr o p orti o nal ma n ner. 
In vitr o, P F - 0 7 0 8 1 5 3 2 was a s u bstrate f or t he he patic u pta ke tra ns p orter, O A T P 1 B 3, b ut n ot 
f or O A T P 1 B 1. C oa d mi n istrati o n of a n O A T P i n hi bit or wit h P F-0 7 0 8 1 5 3 2 i n m o n ke y s 
res ulte d i n a n ota ble i ncrease i n t he plas ma A U C e x p os ure of P F-0 7 0 8 1 5 3 2 a n d 
c orres p o n di n g decrease i n C L , s u g gesti n g a p ote ntial r ole f or O A T P tra ns p ort i n t he 
u pta ke -li mite d C L i n m o n ke ys.
Preli m i nar y e val uati o n of t he i n vitr o meta b olis m of P F-0 7 0 8 1 5 3 2 s h o we d si milar meta b olic 
pr ofiles acr oss s pecies wit h n o e vi de nce of h u ma n s pecific meta b olites. P F -0 7 0 8 1 5 3 2 was 
e xte nsi vel y meta b olize d via o xi dati ve C Y P a n d c o nj u gati o n U G T pat h wa ys.
C Y P -me diate d 
meta b olis m acc o u nte d f or 6 7 % of t he he patic meta b olis m, wit h C Y P 3 A ( 3 1 %) bei n g t he 
pre d o mi na nt C Y P is of or m. T he c o ntri b uti o n of n o n - C Y P meta b olis m was esti mate d t o be 
3 3 % of t he he patic meta b olis m, w hic h was d ue t o gl uc ur o ni dati o n ( 2 4 %) a n d c he mical 
h y dr ol ys is ( 9 %). U G T 1 A 1 a n d U G T 1 A 3 were pri maril y  res p o nsi ble f or t he gl uc ur o ni dati o n 
of P F -0 7 0 8 1 5 3 2, wit h p ossi ble mi n or c o ntri b uti o ns b y  t he n o n-he patic U G T is of or ms, 
U G T 1 A 7 a n d U G T 1 A 8.
Usi n g a p h ys i ol o gically rele va nt static mec ha nistic m o del, P F - 0 70 8 1 5 3 2 was s h o w n t o ha ve 
t he p ote ntial t o be a re versi ble i n hi bitor of U G T 1 A 1 a n d a m o derate ti me-de pe n de nt i n hi bit or 
of C Y P 2 C 1 9 acti vit y  at a cli nical d ose of 2 6 0 m g .  
After e val uati n g t he a bilit y  t o i n d uce C Y P e nz ymes, P F - 0 7 0 8 1 5 3 2 elicite d a wea k i n d ucti o n
of C Y P 3 A 4 a n d C Y P 2 B 6 m R N A i n a si n gle l ot of he pat oc y tes, a n d di d n ot elicit a > 2 -f ol d
i n d ucti o n of C Y P 1 A 2 m R N A or e nz yme acti vit y . Alt h o u g h P F -0 7 0 8 1 5 3 2 de m o nstrate d
> 2 -f ol d C Y P 3 A 4 a n d C Y P 2 B 6 m R N A i n d ucti o n, t he res p o nses lac ke d c o nce ntrati o n
de pe n de n c y, t heref ore, P F- 0 7 0 8 1 5 3 2 was n ot a n i n vitr o i n d ucer of C Y Ps 3 A 4, 2 B 6, or 1 A 2.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 2
Refer t o t he I B f or m ore details o n t he n o ncli nical P K a n d meta b olis m of P F - 0 7 0 8 1 5 3 2.
2. 2. 3. N o ncli nic al S afet y
Refer t o t he I B f or m ore details o n t he n o ncli nical safet y of P F - 0 7 0 8 1 5 3 2.
2. 2. 4. Cli nic al O ver vie w a n d S afet y
As of iss ua nce of t his pr ot oc ol, t w o P hase 1 st u dies e val uati n g P F -0 7 0 8 1 5 3 2 ha ve bee n
c o m plete d. I n t otal, 8 8 partici pa nts ha ve bee n ra n d o mize d i ncl u di n g 2 2 healt h y a d ult
partici pa nts, 5 1 a d ult partici pa nts wit h T 2 D M, a n d 1 5 a d ult partici pa nts wit h o besit y . A t otal
of 7 4 u ni q ue partici pa nts ha ve bee n e x p ose d t o at least 1 d ose of P F- 0 7 0 8 1 5 3 2. T he s afet y
pr ofile of P F - 0 7 0 8 1 5 3 2 was assesse d i n t hese 2 c o m plete d cli nical st u dies a n d, t o date,
a d mi nistrati o n of P F - 0 7 0 8 1 5 3 2 at si n gle d oses u p t o 2 0 0 m g a n d m ulti ple d oses u p t o 
1 8 0 m g Q D has bee n c o nsi dere d safe, wit h t he maj orit y  of t he T E A Es bei n g mil d i n 
i nte nsit y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 3
O ne P hase 1 st u d y, C 3 9 9 1 0 0 3, rece ntl y c o ncl u de d. T his i n patie nt st u d y  e nr olle d partici pa nts
wit h T 2 D M i na de q uately c o ntr olle d o n metf or mi n, a n d partici pa nts wit h o besit y , t o recei ve
P F -0 7 0 8 1 5 3 2 or place b o Q D f or 4 2 da ys. T he starti n g d ose f or t he first c o h ort of t his st u d y
was 2 0 m g Q D of P F - 0 7 0 8 1 5 3 2, wit h s u bse q ue nt d ose le vels deter mi ne d base d o n e mer gi n g
data; t he ma xi m u m d ose a d mi nistere d was 8 0 m g Q D. 
W hile fi nal cli nical data fr o m t his
st u d y are n ot yet a vaila ble, as of iss ua nce of t h is pr ot oc ol, t here ha ve bee n n o deat hs, S A Es
or A Es of se vere i nte nsit y  re p orte d.
Refer t o t he I B f or m ore details o n t he cli nical safet y  of P F- 0 7 0 8 1 5 3 2.
2. 2. 4. 1. Cli nic al P h ar m ac o ki netics
T he cli nical P K of P F -0 7 0 8 1 5 3 2 i n a d ult partici pa nts ha ve bee n e val uate d t o date i n 
2 c o m plete d st u dies ( C 3 9 9 1 0 0 1 a n d C 3 9 9 1 0 0 2).
T he res ults of t hese c o m plete d st u dies are 
s u m marize d i n t he P F-0 7 0 8 1 5 3 2 I B.  
I n St u dy C 3 9 9 1 0 0 1 f oll o wi n g a d mi nistrati o n of si n gle oral d oses of P F-0 7 0 8 1 5 3 2 u n der 
faste d c o n diti o ns t o healt h y  partici pa nts, P F -0 7 0 8 1 5 3 2 was a bs or be d relati vel y  ra pi dl y wit h a 
me dia n T ma x of 1. 0 0 t o 4. 0 2 h o urs (i n di vi d ual T ma x val ues ra n ge d bet wee n 0. 5 a n d 6 h o urs).
Base d o n t he i n di vi d ual plas ma c o nce ntrati o n -ti me pr ofiles, t he a bs or pti o n p hase e x hi bite d 
m ulti ple pea ks, e s peciall y at t he hi g her d ose le vels. Mea n t
½ ra n ge d fr o m 1 8. 0 3 t o 
2 0. 9 0 h o urs acr oss all d oses. Plas ma C ma x i ncrease d less t ha n pr o p orti o nall y acr oss t he e ntire 
i n vesti gate d d ose ra n ge (fr o m 1 0 m g t o 2 0 0 m g ), w hile plas ma A U Ci nf i ncrease d less t ha n 
pr o p or ti o nall y fr o m 1 0 m g t o 3 0 m g  a n d a p pr o xi matel y pr o p orti o nally fr o m 3 0 m g t o 
2 0 0 m g. I nter-partici pa nt varia bilit y  f or P F-0 7 0 8 1 5 3 2 e x p os ure was l o w t o m o derate a n d 
ra n ge d fr o m 9 % t o 3 6 % C V f or Cma x a n d 1 5 % t o 4 4 % C V f or A U Ci nf acr oss all d oses.
O verall, t he res ults i n dicate t hat P F -0 7 0 8 1 5 3 2 ma y  be a d mi nistere d wit h o ut re gar d t o f o o d.  
I n St u dy C 3 9 9 1 0 0 2 f oll o wi n g a d mi nistrati o n of P F - 0 7 0 8 1 5 3 2, Cma x was o bser ve d at 1 t o 
2 h o urs o n Da y  1, a n d 2 t o 8 h o urs f oll o wi n g t he last d ose o n Da y 2 8 or 4 2. Acr oss all d ose 
gr o u ps, t he mea n t ½ ra n ge d fr o m 2 0. 7 0 t o 2 6. 5 0 h o urs. P F -0 7 0 8 1 5 3 2 e x p os ure ge nerall y 
i ncrease d i n a n a p pr o xi matel y d ose pr o p orti o nal ma n ner acr oss t he d ose ra n ge st u die d, a n d 
acc u m ulati o n of less t ha n 2. 1- f ol d was o bser ve d. Uri nar y  rec o ver y of u nc han ge d 
P F -0 7 0 8 1 5 3 2 was l o w, wit h less t ha n 0. 2 % of t he d ose rec o vere d i n t he 2 4 -h o ur d osi n g 
i nter val f oll o wi n g last d ose a d mi nistrati o n. I nter-partici pa nt varia bilit y f or P F - 0 7 0 8 1 5 3 2 
e x p os ure ra n ge d fr o m 1 7 % t o 5 1 % C V f or Cma x a n d 1 5 % t o 6 2 % C V f or A U C ta u acr oss all 
d oses .  N o s u bsta ntial differe nces i n P F -0 7 0 8 1 5 3 2 e x p os ure ( C ma x a n d A U C ta u) were 
o bser ve d bet wee n partici pa nts wit h T 2 D M a n d o besit y  eit her after si n gle d ose ( Da y 1, 
1 0 m g) or m ulti ple d ose ( Da y  2 8, 1 2 0 m g a n d Da y 4 2, 1 8 0 m g) a d mi nistrati o n.
Refer t o t he I B f or m ore details o n t he cli nical P K of P F - 0 7 0 8 1 5 3 2.
2. 3. Be nefit/ Ris k Assess me nt
P F - 0 7 0 8 1 5 3 2 is n ot e x pecte d t o pr o vi de a ny l o n g-ter m cli nical be nefit t o t he healt h y a d ult  
fe male partici pa nts i n t his st u d y.  T his st u d y is desi g ne d pri maril y t o 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 4
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A Es of P F -0 7 0 8 1 5 3 2 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.  
T he S R S D f or t he site s o urce d mi daz ola m ( mi daz ola m h y dr oc hl ori de s yr u p), o me praz ole, 
a n d O C ( 0. 1 5 m g L E / 0. 0 3 m g E E ) pr o d ucts are t he c orres p o n di n g U S PI s.1 3 ,1 4 ,1 5 T he S R S D 
f or t he se ma gl uti de (prefille d, si n gle -use pe ns, d oses 0. 2 5 t o 2. 4 m g ) pr o d uct(s) are t he
c orres p o n di n g U S PI s.1 6 ,1 7
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 P F -0 7 0 8 1 5 3 2 a n d se m a gl uti de
T h yr oi d C -cell t u m ors
T he p ote ntial ris ks are base d o n pr o d uct 
la beli n g f or i njecta ble G L P-1 R a g o nists 
(ie, lira gl uti de, d ula gl uti de, se ma gl uti de, 
a n d e xe nati de) d ue t o d ose -de pe n de nt 
a n d treat me nt d urati o n -de pe n de nt 
t h yr oi d C-cell t u m ors i n n o ncli nical 
st u dies i n rats a n d mice at cli nicall y 
rele va nt e x p os ures. 
Of n ote, si milar t u m ors were n ot see n i n 
r o de nt st u dies wit h P F-0 7 0 8 1 5 3 2 , li kel y 
as P F-0 7 0 8 1 5 3 2 d oes n ot sti m ulate 
r o de nt G L P-1 rece pt ors .
P ote ntial partici pa nts wit h a 
pers o nal or fa mil y hist or y of 
me d ullar y t h yr oi d carci n o ma or 
M ulti ple E n d ocri ne Ne o plasia 
s y n dr o me t y pe 2 are e xcl u de d fr o m 
t he cli nical de vel o p me nt pr o gra m.  
T h yr oi d f u ncti o n tests are i ncl u de d 
i n t he cli nical trial pr ot oc ols t o 
m o nit or partici pa nts’ t h yr oi d 
f u ncti o n.  
Pa ncreatitis
T he p ote ntial ris ks are base d o n pr o d uct 
la beli n g f or i njecta ble G L P-1 R a g o nists 
(ie, lira gl uti de, e xe nati de, se ma gl uti de
a n d d ula gl uti de). 
O ne S A E of o bstr ucti ve p a ncreatitis has 
bee n o bser ve d i n t he P F -0 7 0 8 1 5 3 2
cli nical trial pr o gra m, w hic h was 
c o nsi dere d t o be treat me nt -related b y t he 
i n vesti gat or, b ut u nrelate d b y t he 
S p o ns or .
Per e xcl usi o n criteria, p ote ntial 
partici pa nts wit h ac ute pa ncreatitis 
or a hist or y of c hr o nic pa ncreatitis 
are n ot eli gi ble f or st u d y e ntr y.  
Ser u m a m ylase a n d li pase are 
m o nit ore d d uri n g cli nical st u dies.  
H y p o gl yce mia
Cli nical trials wit h i njecta ble G L P -1 R 
a g o nists ha ve n ot de m o nstrate d a n 
i ncrease d ris k f or h y p o gl yce mia.  B ut
w he n a d mi nistere d i n c o m bi nati o n wit h 
a nti -dia betic a ge nts t hat are k n o w n t o 
ha ve a n i ncrease d ris k of h y p o gl yce mia 
(s uc h as i ns uli n or s ulf o n yl ureas), a n 
i ncrease d ris k f or h y p o gl yce mia was 
o bser ve d.  
Partici pa nts wit h o besit y w h o d o n ot 
ha ve c o -e xisti n g T 2 D M w o ul d n ot be 
ta ki n g a nti-dia betic a ge nts a n d t heref ore 
w o ul d n ot be e x pecte d t o ha ve a n 
i ncrease d ris k f or h y p o gl yce mia.  
A l o w o verall fre q ue nc y of ge nerall y 
mil d h y p o gl yce mia has bee n re p orte d i n 
A nti -dia betic me dicati o ns ar e 
pr o hi bite d i n t his st u d y, a n d bl o o d 
gl uc ose is m o nit ore d as a part of t he 
la b assess me nts d uri n g t he st u d y.  
Partici pa nts are i nf or me d a b o ut t he 
si g ns a n d s y m pt o ms of 
h y p o gl yce mia a n d are m o nit ore d 
f or t hese s y m pt o ms d uri n g t he 
st u d y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 5
t he P F-0 7 0 8 1 5 3 2 cli nical de vel o p me nt 
pr o gra m t o date.
I mpair m e nt i n re nal 
f u ncti o n
P ote ntial ris ks are base d o n pr o d uct 
la beli n g f or i njecta ble G L P-1 R a g o nists, 
a n d pre d o mi na ntl y occ ur i n patie nts wit h 
si g nifica nt na usea, v o miti n g, a n d 
de h y drati o n.
I n t he cli nical trial pr o gra m o nl y o ne 
mil d a d verse e ve nt ( Preferre d Ter m 
Bl o o d creati ni ne i ncrease d) has bee n 
o bser ve d.
Per e xcl usi o n criteria, p ote ntial 
partici pa nts wit h si g nifica nt re nal 
i mpair m e nt are n ot eli gi ble f or 
st u d y e ntr y.  
Re nal f u ncti o n is m o nit ore d b y la b 
assess me nts of ser u m B U N , 
creati ni ne a n d e G F R.
H y drati o n will be e nc o ura ge d, a n d 
re d uce d fl ui d i nta ke a n d e vi de nce 
of de h y drati o n , if detecte d , wi ll be
treate d b y cl ose cli nical f oll o w- u p.
Gastr oi ntesti nal a d verse 
reacti o ns
T he p ote ntial ris ks are base d o n pr o d uct 
la beli n g f or i njecta ble G L P-1 R a g o nists 
(ie, lira gl uti de, e xe nati de, se ma gl uti de
a n d d ula gl uti de).
G astr oi ntesti nal A Es , t he maj orit y of 
w hic h were mil d i n se verit y, ha ve bee n 
o bser ve d i n t he cli nical pr o gra m wit h 
P F -0 7 0 8 1 5 3 2 .  I n n o ncli nical st u dies 
wit h P F -0 7 0 8 1 5 3 2 , gastr oi ntesti nal 
a d verse effects were o bser ve d i n rats a n d 
m o n ke ys.
Partici pa nts are m o nit ore d d uri n g 
t he cli nical st u dies t o pre ve nt 
p ote ntial se q uelae of a n y se vere 
gastr oi ntesti nal reacti o ns, 
e g, de h y drati o n.  
H y drati o n will be e nc o ura ge d a n d 
co nc o mita nt me dicati o n f or na usea 
is per mitte d i n t he st u d y.  
P F -0 7 0 8 1 5 3 2 will be titrate d fr o m a
2 0 m g Q D d ose t o 8 0 m g Q D o ver 
2 8 da ys , t he n fr o m 10 0 m g Q D t o 
2 6 0 m g Q D o ver 6 3 da ys i n t he 
st u d y i n a n atte m pt t o mi ni mize 
gastr oi ntesti nal a d verse reacti o ns. 
Dia betic reti n o pat h y 
c o m plicati o ns
T he p ote ntial ris k is base d o n t he pr o d uct 
la beli n g f or t he i njecta ble G L P-1 R 
a g o nist se ma gl uti de a n d d ula gl uti de i n 
patie nts wit h T 2 D M. 
T here are n o n o ncli nical or cli nical data 
i n v ol vi n g P F -0 7 0 8 1 5 3 2 t o s u ggest a n 
i ncrease d ris k of dia betic reti n o pat h y 
c o m plicati o ns.
P ote ntial partici pa nts wit h dia betes 
mellit us are e xcl u de d fr o m t his 
cli nical st u d y.
S uici dal i deati o n a n d 
be ha vi or
T he p ote ntial ris k is base d o n t he pr o d uct 
la beli n g f or t he i njecta ble G L P-1 R
a g o nists lira gl uti de a n d se ma gl uti de f or 
o besit y base d o n l o n g -ter m st u dies.
S uici dal i deati o n has n ot bee n o bser ve d 
i n t he P F-0 7 0 8 1 5 3 2 cli nical st u dies t o 
date.
S uici dal i deati o n a n d be ha vi or, 
al o n g wit h s y m pt o ms of de pressi o n, 
will be m o nit ore d at s pecifie d
i nter vals d uri n g t he st u d y usi n g t he 
C- S S R S a n d P H Q -9 q uesti o n naires, 
wit h referral t o a M H P
f or f urt her 
e val uati o n if nee de d.
C ha n ges i n heart rate 
P ote ntial ris k is base d o n t he pr o d uct 
la beli n g f or t he i njecta ble G L P-1 R 
a g o nists, lira gl uti de a n d se ma gl uti de, f or 
T 2 D M a n d o besit y .
M o dest i ncreases i n H R ha ve bee n n ote d 
i n t he earl y cli nical st u dies wit h 
P F -0 7 0 8 1 5 3 2 , wit h m ost val ues 
r e mai ni n g wit hi n t he n or mal ra n ge .
H R is m o nit ore d d uri n g t he cli nical 
st u d y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 6
Decli nes i n b o d y wei g ht
Decrease d a p petite a n d b o d y wei g ht l oss 
ha ve bee n re p orte d f or mar kete d 
G L P -1 R a g o nists, a n d decli nes i n b o d y 
wei g ht ha ve bee n n ote d at hi g her d oses 
of P F -0 7 0 8 1 5 3 2 .
Wei g ht is c ollecte d at m ulti ple 
ti me p oi nts a n d will be m o nit ore d 
t hr o u g h o ut t he trial.
Ac ute gall bla d der disease
P ote ntial ris k is base d o n t he pr o d uct 
la beli n g f or t he i njecta ble G L P-1 R 
a g o nists, se ma gl uti de a n d lira gl uti de , f or 
T 2 D M a n d o besit y .
Ac ute gall bla d der disease has n ot bee n 
o bser ve d i n t he P F -0 7 0 8 1 5 3 2 cli nical 
trial pr o gra m t o date.
Partici pa nts wit h s y m pt o matic 
gall bla d der disease are e xcl u de d 
fr o m t his cli nical st u d y. 
Partici pa nts are m o nit ore d f or A E s
a n d la b orat or y tests t hat ma y 
s u g gest de vel o p me nt of ac ute 
gall bla d der disease.
St u d y I nter ve nti o n: O m e pr az ole
Hea dac he, a b d o mi nal 
pai n, na usea, diarr hea, 
v o m iti n g, a n d flat ule nce
Ris k base d o n pr o d uct la beli n g.
A s i n gle oral d ose of 2 0 m g is 
a d mi nistere d i n t his st u d y a n d p oses 
mi ni mal ris k.  Partici pa nts will be 
m o nit ore d i n a n i n patie nt cli nical 
researc h u nit.
St u d y I nter ve nti o n: Mi d az ol a m
Res pirat or y de pressi o n
Ris k base d o n pr o d uct la beli n g.
A si n gle oral d ose of 2 m g is 
a d mi nistere d i n t he st u d y a n d p oses 
mi ni mal ris k.  Partici pa nts will be 
m o nit ore d i n a n i n patie nt cli nical 
researc h u nit.
St u d y I nter ve nti o n : O C (L E/ E E )
I ncrease d B P
Ris k base d o n pr o d uct la beli n g.
A si n gle d ose of 0. 1 5 m g L E / 0. 0 3 
m g E E is a d mi nistere d i n t his st u d y 
a n d p oses mi ni mal ris k.  
Partici pa nts will be m o nit ore d i n a n 
i n patie nt cli nical researc h u nit.
Ot her
Ris k of C O VI D -1 9 
e x p os ure d uri n g st u d y
D uri n g t he pa n de mic, st u d y partici pa nts 
c o ul d be i nfecte d wit h t he S A R S -C o V -2 
vir us d uri n g st u d y partici pati o n. T his 
c o ul d lea d t o i ncrease d healt h ris k f or 
t his partici pa nt a n d ot hers i n t he st u d y.
Partici pa nts u n der g o C O VI D -1 9 
s pecific assess me nts pri or t o 
a d missi o n t o st u d y site a n d 
acc or di n g t o t he S o A .
2. 3. 2. Be nefit Assess me nt
W hile P F - 0 7 0 8 1 5 3 2 is n ot e x pecte d t o pr o vi de a n y si g nifica nt l o n g-ter m cli nical be nefit t o 
t he healt h y o bese partici pa nts i n t his relati vel y s h ort-ter m st u d y, p ote ntial be nefits ma y 
i ncl u de wei g ht l oss, recei vi n g me dical e val uati o ns/ assess me nts ass ociate d wit h cli nical 
st u d y visits (e g, p h y sical e xa mi nati o ns, E C Gs, la bs), a n d c o ntri b uti n g t o t he pr ocess of 
de vel o pi n g a p ote ntial ne w t hera p y f o r T 2 D M a n d o besit y.
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A Es of P F -0 7 0 8 1 5 3 2 ma y  be f o u n d i n t he I B, w hic h is S R S D, f or t his st u d y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 7
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
T he S p o ns or c o nsi ders t hat t he a vaila ble i nf or mati o n fr o m t he n o ncli nical st u dies a n d t he 
cli nical st u dies c o m plete d t o date wit h P F -0 7 0 8 1 5 3 2 c o m prises a be nefit -ris k pr ofile t hat 
s u p p orts t he c o nti n ue d cli nical i n vesti gati o n of t he c o m p o u n d as a p ote ntial o pti o n f or t he 
treat me nt of T 2 DM a n d o besit y .  C o nsi deri n g t he meas ures t o mi ni mize ris k t o st u d y
partici pa nts , t he p ote ntial ris ks i de ntifie d i n ass ociati o n wit h P F - 0 7 0 8 1 5 3 2 are j ustifie d b y 
t he a ntici pate d be nefits t hat ma y be aff or de d t o partici pa nts wit h o besit y .
3. O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
C o h ort 1
Pri m ar y: 
Pri m ar y: 

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n t he
p har mac o ki netics of mi daz ola m, o me praz ole, 
a n d a n oral c o ntrace pti ve ( O C; le v o n or gestrel 
[ L E]/et hi n yl estra di ol [ E E]) i n o bese a d ult 
fe male partici pa nt s.

Mi daz ola m plas ma p har m ac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o ds 1, 4 a n d 7.

O m e praz ole plas ma p har mac o ki netic 
para meters: A U C i nf (if data per mit* ot her wise 
A U C last) i n Peri o ds 1, 4 a n d 7.

L E plas ma p har mac o ki netic para meters: A U C i nf
(if data per mit* o t her wise A U Clast) i n Peri o ds 2 , 
5 a n d 8 .

E E plas ma p har mac o ki netic para meters: A U C i nf
(if data per mit* o t her wise A U Clast) i n i n Peri o ds 
2 , 5 a n d 8 .
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
P F - 07 0 8 1 5 3 2 a d mi nistere d se paratel y a n d i n 
c o m bi nati o n wit h mi daz ola m, o me praz ole, a n d 
a n O C ( L E/ E E) i n o bese a d ult fe male 
partici pa nts .

Assess me nt of T E A Es , cli nical la b orat or y 
a b n or malities, a n d b o d y wei g ht .

Assess me nt of me ntal healt h as deter mi ne d b y 
C- S S R S a n d P H Q - 9. 

T o e val uate t he p har mac o ki netics of S D 
mi daz ola m f oll o wi n g t he disc o nti n uati o n of 
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n i n o bese a d ult 
fe male partici pa nts .  

Mi daz ola m plas ma p har m ac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o d 9.

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n 
a d diti o nal p har mac o ki netic para meters of 
mi daz ola m , o me praz ole, a n d a n O C ( L E/ E E) i n 
o bese a d ult fe male partici pa nts.

A d diti o nal plas ma p har mac o ki netic para meters 
f or mi daz ola m a n d o me praz ole ( Peri o ds 1, 4 a n d 
7) , a n d L E a n d E E ( Peri o ds 2, 5 a n d 8): Cm a x a n d 
T ma x ; a n d C L/ F, Vz/ F, t½ , as data per mit.

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n t he 
meta b olite/ pare nt rati os f or mi daz ola m a n d 
o m e praz ole i n o bese a d ult fe male partici pa nts.

M R A U C
i nf ( 1-h y dr o x y mi daz ola m 
A U C i nf/ mi daz ola m A U Ci nf).

M R A U C
i nf ( 5-h y dr o x y o m e praz ole
A U C i nf/o m e praz ole A U C i nf).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 8

T o e val uate t he M D p har mac o ki netics of 
P F - 07 0 8 1 5 3 2 i n o bese a d ult fe male partici pa nts.

P F - 07 0 8 1 5 3 2 plas ma p har mac o ki netic 
para meters at Da ys 3 4 a n d 1 0 3: A U C 2 4, Cma x , 
T ma x .
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 t he effects of P F - 07 0 8 1 5 3 2 o n t he 
p har mac o ki netics of 1 -h y dr o x y mi daz ola m i n 
o bese a d ult fe male partici pa nts.

1- h y dr o x y mi daz ola m plas ma p har mac o ki netic 
para meters: A U C last, Cma x , Tma x; a n d A U Ci nf a n d 
t½ as data per mit i n Peri o ds 1 , 4 a n d 7 .  

Meta b olite/ pare nt 
( 1-h y dr o x y mi daz ola m/ mi daz ola m) rati os f or 
A U C i nf (as data per mit), A U Clast, a n d Cma x will 
als o be calc ulate d.

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n t he 
p har mac o ki netics of 5- h y dr o x y o me praz ole i n 
o bese a d ult fe male partici pa nts. 

5- h y dr o x y o me praz ole plas ma p har mac o ki netic 
para meters: A U C last, Cma x , Tma x; a n d A U Ci nf a n d 
t½ as data per mit i n Peri o ds 1, 4 a n d 7.  

Meta b olite/ pare nt ( 5- h y dr o x y o me praz ole
/o m e praz ole ) rati os f or A U Ci nf (as data per mit), 
A U C last, a n d Cma x will als o be calc ulate d. 

T o e val uate t he effects of P F - 07 0 8 1 5 3 2 o n 
bi o mar kers of C Y P 3 A i n d ucti o n. [ O pti o nal] .

M or ni n g pre d ose 
4 β -h y dr o x yc h olester ol/c h olester ol plas ma rati o 
o n Da y 1 i n Peri o ds 1, 4, a n d 7.  
C o h ort 2
Pri m ar y: 
Pri m ar y: 

T o e val uate t he effects of se ma gl uti de 
(s u bc uta ne o us se ma gl uti de) o n t he S D P K of 
mi daz ola m i n o bese a d ult fe male partici pa nts.

Mi daz ola m plas ma p har mac o ki netic para m eters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o ds 1 a n d 3 .
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he safet y a n d t olera bilit y of 
se ma gl uti de a d mi nistere d se paratel y a n d i n 
c o m bi nati o n wit h mi daz ola m i n o bese a d ult 
fe male partici pa nts.

Assess me nt of T E A Es , cli nical la b orat or y 
a b n or malities, a n d b o d y wei g ht .

Assess me nt of me ntal healt h as deter mi ne d b y 
C- S S R S a n d P H Q -9.

T o e val uate t he p har mac o ki netics of S D 
mi daz ola m f oll o wi n g t he disc o nti n uati o n of 
se ma gl uti de a d mi nistrati o n i n o bese a d ult 
fe male partici pa nts .

Mi daz ola m plas ma p har m ac o ki netic para meters: 
A U C i nf (if data per mit* ot her wise A U C last) i n 
Peri o d 4.

T o e val uate t he effects of se ma gl uti de o n 
a d diti o nal p har mac o ki netic para meters of 
mi daz ola m i n o bese a d ult fe male partici pa nts .

A d diti o nal plas m a p har m ac o ki netic para meters 
f or mi daz ola m (i n Peri o ds 1 a n d 3): Cma x , Tma x ,
a n d C L/ F, Vz/ F, t ½ as data per mit.

T o e val uate t he effects of se ma gl uti de o n t he 
meta b olite/ pare nt rati o f or mi daz ola m i n o bese 
a d ult fe male partici pa nts.

M R A U C
i nf ( 1-h y dr o x y mi daz ola m 
A U C i nf/ mi daz ola m A U Ci nf).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 9
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 t he effects of se ma gl uti de o n t he 
p har mac o ki netics of 1 -h y dr o x y mi daz ola m i n 
o bese a d ult fe male partici pa nts.

1- h y dr o x y mi daz ola m plas ma p har mac o ki netic 
para meters: A U C last, Cma x , Tma x; a n d A U Ci nf a n d 
t½ as data per mit i n Peri o ds 1 a n d 3 .  

Meta b olite/ pare nt 
( 1-h y dr o x y mi daz ola m/ mi daz ola m) rati os f or 
A U C i nf (as data per mit), A U Clast, a n d Cma x will 
als o be calc ulate d.

T o e val uate t he effects of se ma gl uti de o n 
bi o mar kers of C Y P 3 A i n d ucti o n. [ O pti o nal]

M or ni n g pre d ose 
4 β -h y dr o x yc h olester ol/c h olester ol plas ma rati o 
o n Da y 1 i n Peri o ds 1 a n d 3.  
* S h o ul d it be dee me d t hat t o o fe w A U C i nf esti mates (e g, less t ha n 1 2 f or a si n gle treat me nt) are o btai ne d 
fr o m t he e val ua ble partici pa nts, A U Clast ma y be selecte d as t he pri mar y e n d p oi nt f or C S R re p orti n g.  T his 
will be c o nsi dere d f or t he mi daz ola m , 1-h y dr o x y mi daz ola m, o me praz ole, 5 -h y dr o x y o me praz ole, L E, a n d E E
o bjecti ves se paratel y.
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his st u d y will be c o n d ucte d wit h 2 c o h orts .  C o h ort 1 will e val uate t he effect of 
2 stea d y-state d ose le vels of P F -0 7 0 8 1 5 3 2 o n t he S D p har mac o ki netics of mi daz ola m , 
o me praz ole, a n d a n O C ( L E/ E E). C o h ort 2 will e val uate t he effect of stea d y-state
se ma gl uti de o n t he S D p har mac o ki netics of mi daz ola m .  Titrati o n will be i m ple me nte d i n 
b ot h c o h orts i n or der t o e nha nce gastr oi ntesti nal t olera bilit y  si milarly t o t he a p pr oac h 
i m ple me nte d f or mar kete d G LP -1 R a g o nists.  Partici pa nts will partici pate i n eit her C o h ort 1 
or C o h ort 2 ( n ot b ot h), a n d C o h ort 1 a n d C o h ort 2 are preferre d t o be c o n d ucte d i n parallel, if 
p ossi ble.
All partici pa nts will pr o vi de i nf or me d c o nse nt a n d u n der g o Scree ni n g e val uati o ns t o 
deter mi ne t heir eli gi bilit y.  Scree ni n g will occ ur wit hi n 2 8 da y s of t he first d ose of st u d y 
i nter ve nti o n o n Da y  1 of Peri o d 1 f or b ot h C o h orts 1 a n d 2 .  Partici pa nts w h o disc o nti n ue 
fr o m t he st u d y bef ore c o m pleti n g all assess me nts 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.
P F -0 7 0 8 1 5 3 2 will be pr o vi de d as ta blets f or oral a d m i nistrati o n.  P F - 0 7 0 8 1 5 3 2 m ust be 
a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes of c o m pleti o n of t he m or ni n g meal.  
P F - 0 7 0 8 1 5 3 2 will be a d mi nistere d first a n d mi daz ola m a n d o me praz ole or t he O C will be 
a d mi nistere d wit hi n 5 mi n utes of P F -0 7 0 8 1 5 3 2 d uri n g t he D DI assess me nt peri o ds.
S e ma gl uti de will be pr o vi de d as pre- fille d, si n gle- d ose pe ns f or s u bc uta ne o us i njecti o n.  
Dr u g a d mi nistrati o n will f oll o w t he i nstr ucti o ns pr o vi de d i n t he a p pr o ve d Hi g hli g hts of 
Prescri bi n g I nf or mati o n as o utli ne d i n t he U S PI . 1 6 ,1 7  Se ma gl uti de m ust be a d mi nis tere d o nce 
wee kl y, prefera bl y i n t he m or ni n g, wit h o ut re gar d t o ti mi n g of t he brea kfast meal d uri n g 
o ut patie nt visits t o t he C R U f or d ose a d mi nistrati o n.  D uri n g t he D DI assess me nt i n patie nt 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 0
visit ( Peri o d 3), se ma gl uti de a n d mi daz ola m m ust be a d mi nistere d wit hi n a p pr o xi matel y  
1 0 mi n utes of c o m pleti o n of t he m or ni n g meal.  S e ma gl uti de will be a d mi nistere d first , a n d 
mi daz ola m will be a d mi nistere d wit hi n 5 mi n utes of se ma gl uti de.
4. 1. 1. C o h ort 1
C o h ort 1 is a n o pe n-la bel, 9 -peri o d, fi xe d-se q ue nce desi g n t o e val uate t he effect of 
2 stea d y-state d ose le vels of P F - 0 7 0 8 1 5 3 2 o n t he S D p har mac o ki netics of mi daz ola m a n d 
o me praz ole, a d mi nistere d si m ulta ne o usl y , a n d a n O C ( LE/ E E) i n ot her wise healt h y  o bese 
a d ult fe male partici pa nts wit h a B MI ≥3 0 k g/ m 2.  
A p pr o xi m atel y 1 6 partici pa nts will be e nr olle d i n C o h ort 1 .  
T he t otal d urati o n of partici pati o n fr o m t he Scree ni n g Visit t o t he F/U tele p h o ne c o ntact will 
be a p pr o xi matel y  2 7 wee ks; ie, 1 8 8 da y s, of w hic h 1 1 2 da y s will be i n-patie nt as f oll o ws: 
Peri o d 1 ( S D mi daz ola m a n d o me praz ole): 1 da y ; Peri o d 2 ( S D O C): 5 da ys; Peri o d 3 
(P F -0 7 0 8 1 5 3 2 titrate d t o 8 0 m g Q D) : 28 d a y s; Peri o d 4 ( 8 0 m g P F -0 7 0 8 1 5 3 2 + S D 
mi daz ola m a n d o me praz ole ): 1 da y; Peri o d 5 ( 8 0 m g P F -0 7 0 8 1 5 3 2 + S D O C ): 5 da y s; 
Peri o d 6 ( P F -0 7 0 8 1 5 3 2 titrate d t o 2 6 0 m g Q D) : 6 3 da y s; Peri o d 7 ( 2 6 0 m g P F - 0 7 0 8 1 5 3 2
+ S D mi daz ola m a n d o me praz ole ): 1 da y; Peri o d 8 ( 2 6 0 m g  P F -0 7 0 8 1 5 3 2 + S D O C ): 
6 da y s; Peri o d 9 (S D mi daz ola m o nl y ): 2 da ys.
T he F /U o ut- patie nt visit will occ ur 7 -1 0 da y s fr o m t he last d ose of st u d y i nter ve nti o n a n d a 
tele p h o ne F/ U c o ntact will occ ur 2 8 - 3 5 d a y s fr o m t he last d ose of st u d y i nter ve nti o n. 
4. 1. 2. C o h ort 2
C o h ort 2 is a n o pe n-la bel, 4 -peri o d, fi xe d-se q ue nce desi g n t o e val uate t he effect of 
stea d y-state se ma gl uti de o n t he S D P K of mi daz ola m i n o bese a d ult fe male partici pa nts wit h 
a B MI ≥3 0 k g/ m 2.
A p pr o xi matel y  1 6 partici pa nts will be e nr olle d i n C o h ort 2 .
T he t otal d urati o n of partici pati o n fr o m t he Scree ni n g Visit t o t he F/U tele p h o ne c o ntact will 
be a p pr o xi matel y  3 3 wee ks; i .e., 2 2 8 da y s, of w hic h 6 d a y s will be i n-patie nt as f oll o ws:
Peri o d 1 ( S D mi daz ola m): 1 da y ; Peri o d 2 (fi nal da y of se ma gl uti de treat me nt ( 2. 4 m g): 
1 da y ; Peri o d 3 ( 2. 4 m g se ma gl uti de o nce wee kl y + S D mi daz ola m) 2 da y s; Peri o d 4 
(S D mi daz ola m): 2 da y s.  Partici pa nts will als o be re q uire d t o ret ur n t o t he cli nic d uri n g 
o ut- patie nt visits , prefera bl y i n t he m or ni n g, t o recei ve t heir o nce wee kl y se ma gl uti de
i njecti o ns ( Peri o d 2).
T he o ut- patie nt F/ U visit will occ ur 7 -1 0 da y s fr o m t he last d ose of st u d y  i nter ve nti o n a n d a
tele p h o ne F/ U c o ntact will occ ur 2 8- 3 5 d a y s fr o m t he last d ose of st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 1
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T he p ur p ose of t his st u d y is t o c haracterize t he effect of P F - 0 7 0 8 1 5 3 2, a d mi nistere d at 
2 stea d y-state d ose le vels, o n t he P K of si n gle d oses of mi daz ola m ( 2 m g oral ) a n d
o me praz ole ( 2 0 m g oral ), a d mi nistere d si m ulta ne o usl y, a n d a n O C (L E 0. 1 5 m g /E E 0. 0 3 m g
oral ) i n ot her wise healt h y  o bese a d ult fe male partici pa nts i n C o h ort 1.  Mi daz ola m a n d 
o me praz ole will be a d mi nistere d si m ulta ne o usl y  t o all o w f or e val uati o n of 2 D DIs wit hi n o ne 
st u d y peri o d. Si m ulta ne o us a d mi nistrati o n of t hese 2 pr o be s u bstrates has bee n vali date d; 
ie, n o D DI a n d s h o w n t o be safe. 1 8 ,1 9 T he i m pact of stea dy- state s u bc uta ne o us se ma gl uti de
o n t he P K of si n gle-d ose mi daz ola m ( 2 m g oral ) will als o be assesse d i n ot her wise healt h y  
o bese a d ult fe male partici pa nts i n C o h ort 2. Ot her wise healt h y o bese a d ult fe males will be 
e nr olle d i n t his st u d y as t he y are o ne of t he tar get p o p ulati o ns f or P F-0 7 0 8 1 5 3 2.  
I n C o h ort 1, titrati o n of P F - 0 7 0 8 1 5 3 2 d oses will be utilize d t o ac hie ve 8 0 m g Q D a n d 
2 6 0 m g Q D .  T he D DI effect will be i nitiall y assesse d at t he P F -0 7 0 8 1 5 3 2 8 0 m g Q D d ose as 
t his is e x pecte d t o be a p ote ntial t hera pe utic d ose f or treat me nt of T 2 D M.  T he D DI effect 
will als o be assesse d at t he 2 6 0 m g Q D d ose as t h is is t he ma xi m u m d ose i n t he P hase 2 
st u d y f or b ot h T 2 D M a n d o besit y . P F -0 7 0 8 1 5 3 2 will be a d mi nistere d f or a d urati o n of 
7 da y s at eac h of t he 8 0 m g Q D a n d 2 6 0 m g Q D d osi n g re gi me ns pri or t o a d mi nistrati o n of 
t he S D mi daz ola m a n d o me praz ole, or O C treat me nts (Ta ble 8 ) t o e ns ure t hat cli nicall y 
rele va nt stea dy -state P F - 0 7 0 8 1 5 3 2 e x p os ures are ac hie ve d .
T itrati o n of se ma gl uti de d oses will be utilize d t o ac hie ve 2. 4 m g i n C o h ort 2, w hic h is t he 
ma xi m u m a p pr o ve d d ose f or wei g ht l oss .  T he D DI effect will be assesse d at t he 2. 4 m g d ose
f oll o wi n g wee kl y titrati o ns f or 4 wee ks eac h at t he 0. 2 5 m g, 0. 5 m g, 1. 0 m g, 1. 7 m g, a n d 
2. 4 m g d oses as i nstr ucte d i n t he U S PI .1 6 ,1 7 S e ma gl uti de will be a d mi nistere d f or o ne 
a d diti o nal wee k ( half-life a p pr o ximatel y  1 wee k) at t he 2. 4 m g d ose t o e ns ure t hat cli nicall y 
rele va nt stea dy- state e x p os ures are ac hie ve d pri or t o a d mi nistrati o n of S D mi daz ola m i n 
Peri o d 3 ( Ta ble 9 ).
A d diti o nall y , partici pa nts i n b ot h c o h orts will be disc har ge d fr o m t he cli nical site f or 2 wee ks 
f oll o wi n g t he fi nal P K sa m ple c ollecti o n of O C ( L E/ E E) i n Peri o d 8, Da y 2 ( C o h ort 1) or 
mi da z ola m i n Peri o d 3, Da y 2 ( C o h ort 2), a n d disc o nti n ue all P F-0 7 0 8 1 5 3 2 or se ma gl uti de 
d osi n g at t hat ti me.  F oll o wi n g t he 2 -wee k o ut- patie nt d urati o n, partici pa nts will ret ur n t o t he 
cli nical site f or a fi nal mi daz ola m assess me nt, wit h o ut eit her P F -0 7 0 8 1 5 3 2 or se ma gl uti de 
c oa d mi nistrati o n. 
4. 2. 1. C o h ort 1 
4. 2. 1. 1. Mi d az ol a m A d mi nistr ati o n
Preli mi nar y  4--h y dr o x yc h olester ol/c h olester ol (bi o mar ker f or C Y P 3 A acti vit y) res ults fr o m 
S t u d y C 39 9 1 0 0 3 wit h P F -0 7 0 8 1 5 3 2 s u g gest a p o te ntial pert ur bati o n of C Y P 3 A acti vit y.  
T heref ore , mi da z ola m will be use d as a “se nsiti ve s u bstrate” of C Y P 3 A i n t his st u d y  t o 
assess t he i m pact of P F -0 7 0 8 1 5 3 2 a d mi nistrati o n o n b ot h mi daz ola m a n d its 1- h y dr o x y  
meta b olite , w hic h is f or me d via C Y P 3 A. T o f urt her i n vesti gate t he mec ha nis m of t his 
i nteracti o n, plas ma 4--h y d r o xyc h olester ol/c h olester ol a n d  
 sa m ples, use d as e n d o ge n o us 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 2
pr o bes f or C Y P 3 A i n d ucti o n, will be c ollecte d i n t his st u d y .  If t here are n o o bser ve d c ha n ges 
i n mi daz ola m e x p os ures d uri n g c o nc o mita nt a d mi nistrati o n of eit her P F -0 7 0 8 1 5 3 2 or 
se ma gl uti de, neit her p las ma 4--h y dr o x yc h olester ol/c h olester ol n or
 sa m ples will be 
a nal yz e d. 
F oll o wi n g assess me nt of t he D DI bet wee n P F -0 7 0 8 1 5 3 2 a n d mi daz ola m , the a d mi nistrati o n 
of P F - 0 7 0 8 1 5 3 2 will be disc o nti n ue d f or a 2-wee k peri o d , after w hic h a n a d diti o nal si n gle 
d ose of mi daz ola m will be a d mi nistere d t o assess t he i m pact of disc o nti n uati o n of 
P F -0 7 0 8 1 5 3 2 a d mi nistrati o n o n mi daz ola m p har mac o ki netics. If i n d ucti o n of C Y P 3 A 
acti vit y is o bser ve d (as deter mi ne d b y mi daz ola m P K d uri n g c oa d mi nistrati o n of 
P F - 0 7 0 8 1 5 3 2), a 2 -wee k peri o d of ti me wit h o ut P F - 0 7 0 8 1 5 3 2 d osi n g is e x pecte d t o be 
s ufficie nt t o all o w C Y P 3 A acti vit y  t o ret ur n t o baseli ne.2 0
Mi daz ola m is ra pi dl y  a bs or be d after oral a d mi nistrati o n a n d is s u bject t o s u bsta ntial i ntesti nal 
a n d he patic first -pass meta b olis m. F o o d effect has n ot bee n teste d usi n g mi daz ola m H Cl 
s yr u p; b ut w he n a 1 5 m g oral ta blet of mi daz ola m was a d m i nistere d wit h f o o d t o a d ults, t he 
a bs or pti o n a n d dis p ositi o n of mi daz ola m was n ot affecte d. T he e xte nt of plas ma pr otei n 
bi n di n g of mi daz ola m is m o deratel y hi g h a n d c o nce ntrati o n i n de pe n de nt. I n a d ults a n d 
pe diatric patie nts ol der t ha n 1 y ear, mi daz ola m is a p pr o xi matel y 9 7 % b o u n d t o plas ma 
pr otei n, pri nci pall y al b u mi n. I n healt h y v ol u nteers, 1- h y dr o x y m i daz ola m is b o u n d t o t he 
e xte nt of 8 9 %. 1 3
Mi daz ola m is pri maril y  meta b olize d i n t he li ver a n d g ut b y h u ma n C Y P 3 A 4 t o its 
p har mac ol o gic acti ve meta b olite, 1- h y dr o x y mi daz ola m, f oll o we d b y  gl uc ur o ni dati o n of t he 
1- h y dr o x y l meta b olite whic h is prese nt i n u nc o nj u gate d a n d c o nj u gate d f or ms i n h u ma n 
plas ma. T he 1- h y dr o x y m i daz ola m gl uc ur o ni de is t he n e xcrete d i n uri ne.  Mi daz ola m is als o 
meta b olize d t o 2 ot her mi n or meta b olites: 4- h y dr o x y  meta b olite (a b o ut 3 % of t he d ose) a n d 
1, 4- di h y dr o x y m eta b olite (a b o ut 1 % of t he d ose) are e xcrete d i n s mall a m o u nts i n t he uri ne 
as c o nj u gates. 1 3
Si x si n gle-d ose p har mac o ki netic st u dies i n v ol vi n g heal t h y a d ults yiel de d p har mac o ki netic 
para meters f or mi daz ola m i n t he f oll o wi n g ra n ges: v ol u me of distri b uti o n, 1 t o 3. 1 L/ k g; 
eli mi nati o n half -life, 1. 8 t o 6. 4 h o urs ( mea n a p pr o xi matel y 3 h o urs); a n d t otal cleara nce, 
0. 2 5 t o 0. 5 4 L/ hr/ k g. I n a st u d y c o m parin g n or mal ( n = 2 0) a n d o bese patie nts ( n = 2 0) t he 
mea n half -life was greater i n t he o bese gr o u p ( 5. 9 h o urs vs. 2. 3 h o urs), w hic h was attri b ute d 
t o a n i ncrease of a p pr o xi matel y 5 0 % i n t he v ol u me of distri b uti o n c orrecte d f or t otal b o d y 
wei g ht. 1 3 ,2 1 ,2 2 Plas ma sa m ples f or mi daz ola m a n d 1-h y dr o x y -mi daz ola m will be c ollecte d i n 
t his st u d y f or u p t o 2 4 h o urs after d osi n g, w hic h is e x pecte d t o be a de q uate e ve n wit h t he 
l o n ger eli mi nati o n half -life i n o bese s u bjects. 
Si n gle oral d oses of mi daz ola m ra n gi n g fr o m 2 t o 7. 5 m g ha ve bee n safel y a d mi nistere d t o 
healt h y  partici pa nts i n pre vi o us i nter nal Pfizer dr u g-dr u g i nteracti o n st u dies ( A 5 3 5 1 0 1 2, 
B 3 2 9 1 0 2 3, B 7 4 5 1 0 2 2, C 1 0 6 1 0 1 6) .  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 3
4. 2. 1. 2. O me pr az ole A d mi nistr ati o n
A d ults wit h T 2 D M a n d o besit y ofte n re q uire treat me nt f or G E R D , t heref ore, it is li kel y t hat 
P F - 0 7 0 8 1 5 3 2 will be c oa d mi nistere d wit h o me praz ole i n cli nical practice.  A d diti o nall y , 
P F - 0 7 0 8 1 5 3 2 was s h o w n t o be a m o derate i n vitr o ti me- de pe n de nt i n hi bit or of C Y P 2 C 1 9 at a 
cli nical d ose of 2 6 0 m g. T heref ore, o me praz ole will be use d as a “se nsiti ve s u bstrate” of 
C Y P 2 C 1 9 i n t his st u d y t o assess t he i m pact of P F- 0 7 0 8 1 5 3 2 a d mi nistrati o n o n t he P K of 
b ot h o me praz ole a n d its 5- h y dr o x y  meta b olite, w hic h is f or me d via C YP 2 C 1 9 . 
O me praz ole a bs or pt i o n is ra pi d, wit h pea k plas ma le vels occ urri n g wit hi n 0. 5 t o 3. 5 h o urs. 
Pea k plas ma c o nce ntrati o ns of o me praz ole a n d A U C are a p pr o xi matel y  d ose pr o p orti o nal u p 
t o 4 0 m g. A bs ol ute bi oa vaila bilit y  is a b o ut 3 0- 4 0 % at d oses of 2 0-4 0 m g, d ue i n lar ge part t o 
pres ys te mic meta b olis m. I n healt h y s u bjects t he plas ma half-life is 0. 5 t o 1 h o ur, a n d t he 
t otal b o d y cleara nce is 5 0 0-6 0 0 m L / mi n. Pr otei n bi n di n g is a p pr o xi matel y  9 5 %.1 4
O me praz ole is e xte nsi vel y  meta b olize d b y C Y P 4 5 0 , wit h C Y P 2 C 1 9 bei n g t he pri mar y 
pat h wa y res ulti n g i n f or mati o n of 5-h y dr o x y o me praz ole .  C Y P 3 A 4 is a mi n or meta b olic 
pat h wa y res ulti n g i n t he f or mati o n of t he o me praz ole s ul p h o ne . A p pr o xi matel y  2-3 % of 
Ca ucasia n , 2 % of Africa n A merica ns , a n d 11 – 2 3 % of Asia n p o p ulati o ns are C Y P 2 C 1 9 p o or 
meta b olizers ( P M), t heref ore, C Y P 3 A is t he pre d o mi na nt meta b olic r o ute i n t hese 
i n di vi d uals.2 3 I n p har mac o ki netic st u dies of si n gle 2 0 m g o me praz ole d oses, a n i ncrease i n 
A U C of a p pr o xi matel y  4-f ol d was n ote d i n Asia n s u bjects c o m pare d wit h Ca ucasia ns. 1 4
F oll o wi n g si n gle -d ose oral a d mi nistrati o n of a b uffere d s ol uti o n of o me praz ole, little if a n y  
u nc ha n ge d dr u g was e xcrete d i n uri ne. M ost of
t he d ose (a b o ut 7 7 %) was eli mi nate d i n uri ne 
as at least 6 meta b olites . T w o were i de ntifie d as h y dr o x y o m e praz ole a n d t he c orres p o n di n g 
car b o x yl ic aci d. T he re mai n der of t he d ose was rec o vera ble i n feces. T his i m plies a 
si g nifica nt biliar y e xcreti o n of t he meta b olites of o me praz ole. T hree meta b olites ha ve bee n 
i de ntifie d i n plas ma; t he s ulfi de a n d s ulf o ne deri vati ves of o me praz ole, a n d 
h y dr o x y o m e praz ole. T hese meta b olites ha ve ver y  little or n o a ntisecretor y  acti vit y.1 4
Beca use t he eli mi nati o n half-li ves of o me praz ole a n d its 5 -h y dr o x y  meta b olit e ra n ge fr o m 
0. 5 t o 1 h o ur f oll o wi n g si n gle d oses ,2 4 plas ma will be c ollecte d f or 2 4 h o urs after d osi n g f or 
deter mi nati o n of P K para meters .  
O me praz ole is ge nerall y well-t olerate d by healt h y i n di vi d uals f oll o wi n g si n gle, oral, d oses of
1 0 m g 2 5 a n d 2 0 m g .2 6 I n a d diti o n, t he safet y of o me praz ole f or t he treat me nt of gastric ulcer
disease has bee n esta blis he d at d oses as hi g h as 4 0 m g o nce dail y f or 4 t o 8 wee ks .  A d verse 
reacti o ns ha ve us ually bee n mil d a n d tra nsie n t.  F or m ore c o m plete i nf or mati o n, please refer
t o t he U SPI f or o me praz ole .1 4
4. 2. 1. 3. Or al C o ntr ace pti ve A d mi nistr ati o n
T he estr o ge ns a n d pr o gesti ns c o ntai ne d i n oral c o ntrace pti ves are s u bstrates f or C Y P 3 A 4/ 5
a n d ot her i n d uci ble meta b olic e nz y mes.  Beca use t he a ntici pate d tar get p o p ulati o n f or 
P F -0 7 0 8 1 5 3 2 will i ncl u de fe males of c hil d beari n g p ote ntial w h o ma y  use a n O C, a t hir d 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 4
o bjecti ve of t his st u d y  is t o esti mate t he effect of a d mi nistrati o n of 8 0 m g Q D a n d 26 0 m g
Q D P F -0 7 0 8 1 5 3 2 o n t he S D P K of a n O C c o ntai ni n g 0. 1 5 m g  LE a n d 0. 0 3 m g E E.  
T he mea n ( S D) half -li ves of L E a n d E E are 2 9. 8 ( 8. 3) a n d 1 5. 4 ( 3. 2) h o urs ,1 5 res pecti vel y; 
t heref ore, plas ma will be c ollecte d f or u p t o 1 2 0 h o urs after d osi n g f or deter mi nati o n of P K 
para meters.  T he effect of f o o d o n t he rate a n d t he e xte nt of L E a n d E E a bs or pti o n f oll o wi n g 
oral a d mi nistrati o n of L E a n d E E ta blets has n ot bee n e val uate d. 1 5
Oral c o ntrace pti ve use has bee n s h o w n t o ca use a n i ncrease i n B P t hat i s re versi ble w he n t he
oral c o ntrace ptive is disc o nti n ue d.  T he use of a n O C a ge nt c o ntai ni n g 3 0 µ g E E a n d 1 5 0 u g 
L E was ass ociate d wit h a s mall i ncrease i n b ot h syst olic a n d diast olic B P .2 7 Alt h o u g h t he 
ris k of i ncrease d B P is e x pecte d t o be s mall f oll o wi n g S D a d mi nistrati o n of t he O C i n t his 
st u d y, B P effects res ulti n g fr o m c oa d mi nistrati o n of P F-0 7 0 8 1 5 3 2 wit h t he O C will be 
m o nit ore d as descri be d bel o w .  F or m ore c o m plete i nf or mati o n, please refer t o t he U S PI f or 
t he O C.1 5
4. 2. 1. 4. P F -0 7 0 8 1 5 3 2 A d mi nistr ati o n
A de nse P K pr ofile will be c ollecte d f or P F- 0 7 0 8 1 5 3 2 after reac hi n g t he tar get d oses of 
P F - 0 7 0 8 1 5 3 2 f or eac h D DI assess me nt; ie, 80 m g i n Peri o d 3, Da y  2 8 a n d 26 0 m g i n 
Peri o d 6, Da y 6 3 , t o better u n dersta n d t he P K i n o bese fe male partici pa nts.
P F - 0 7 0 8 1 5 3 2 will be a d mi nistere d via 7- d a y ( 1-wee k) titrati o n i ncre me nts u p t o t he 
8 0 m g Q D re gi me n i n Peri o d 3 pri or t o t he a d mi nistrati o n of mi daz ola m a n d o me praz ole i n 
Peri o d 4, a n d t he O C i n Peri o d 5.  L i ke wise, P F -0 7 0 8 1 5 3 2 will be a d mi nistere d via 1- wee k
titrati o n i ncre me nts u p t o t he 26 0 m g Q D re gi me n i n Peri o d 6 pri or t o a d mi nistrati o n of 
mi daz ola m a n d o me praz ole i n Peri o d 7, a n d t he O C i n Peri o d 8 ( Secti o n 6. 1. 1 , Ta ble 8 ). T he 
P F - 0 7 0 8 1 5 3 2 d osi n g re gi me n is desi g ne d t o ac hie ve a n d mai ntai n P K stea d y -state f or 
a p pr o xi matel y 7 d a y s pri or t o assess me nt of t he i nteracti o n wit h t he 3 s u bstrates.   T his will 
e na ble a n y i nteracti o n t hat is prese nt t o be assesse d u n der c o n diti o ns t hat are e x pecte d t o 
i ncrease t he p ote ntial f or ma xi mal C Y P 3 A i n d ucti o n a n d/ or C Y P 2 C 1 9 i n hi biti o n at t he 
P F - 0 7 0 8 1 5 3 2 d oses bei n g st u die d s h o uld t his occ ur . Base d o n e mer gi n g data fr o m ot her 
cli nical st u dies t hat ma y bec o me a vaila ble d uri n g t he c o n d uct of t his st u d y, t he titrati o n rate, 
i ncre me ntal i ncreases i n d ose, a n d/ or t he P F -0 7 0 8 1 5 3 2 d oses at w hic h t he mi daz ola m a n d
o me praz ole, or O C P K i nteracti o ns are e val uate d ma y be a dj uste d.  
D osi n g of P F - 0 7 0 8 1 5 3 2 ( wit h or wit h o ut mi daz ola m , o me praz ole, or t he O C ) is pla n ne d t o 
occ ur i n t he fe d state wit h a sta n dar d brea kfast, as t his is t he a ntici pate d m o de of 
a d mi nistrati o n i n cli nical use.  
4. 2. 2. C o h o rt 2
4. 2. 2. 1. Se m a gl uti de a n d Mi d az ol a m A d mi nistr ati o n
O besit y  has l o n g bee n ass ociate d wit h a state of c hr o nic, l o w -le vel i nfla m mati o n,2 8 ,2 9 ,3 0 wit h
adi p ose tiss ue bei n g o ne of t he mai n s o urces of i nfla m mat or y  me diat ors, i ncl u di n g I L- 6.3 1
A di p ose tiss ue has bee n descri be d as a n acti ve e n d ocri ne or ga n t hat secretes si g nali n g 
m olec ules i n v ol ve d i n t he re g ulati o n of i ns uli n se nsiti vit y , f o o d i nta ke a n d i nfla m mati o n. T o 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 5
t hat e n d, decreases i n I L - 6 a n d ot her i nfla m mat or y me diat ors ha ve bee n o bser ve d f oll o wi n g 
wei g ht l oss i n o bese i n di vi d uals, w het her it be a res ult of cal oric deficit or bariatric 
s ur ger y.3 2 ,3 3 ,3 4
I nfla m mat or y c yt o ki nes, s uc h as I L- 6, I L- 1, a n d T N Fα ha ve bee n s h o w n t o i n hi bit C Y P 3 A 
acti vit y. I n dee d, I L-6 is t he tar get f or dr u gs s uc h as saril u ma b a n d t ociliz u ma b use d t o treat
R A, a disease k n o w n t o ha ve a hi g h i nfla m mat or y b ur de n.  T he e x p os ure of si m vastati n, a 
C Y P 3 A s u bstrate, was decrease d by 4 5 % a n d 5 7 % , res pecti vely, d uri n g a d mi nistrati o n of 
saril u ma b or t ociliz u ma b. T his o bser vati o n was li kel y  d ue t o t he atte n uati o n of t he i n hi bit or y 
i m pact of I L-6 o n C Y P 3 A acti vit y , t h us, res ulti n g i n a ret ur n t o baseli ne or a “ n ormalizati o n” 
of e nz y me acti vit y.3 5 ,3 6
Pri or p u blicati o ns ha ve de m o nstrate d l o wer cleara nce of C Y P 3 A s u bstrates, i ncl u di n g 
mi daz ola m, i n partici pa nts wit h o besit y .2 1 ,3 7 F urt h er m ore, a n u m ber of cli nical st u dies ha ve 
de m o nstrate d i ncrease d cleara nce of C Y P 3 A s u bstrates f oll o wi n g wei g ht l oss. 3 8 ,3 9 ,4 0  F or 
e xa m ple, one y ear after bariatric s ur ger y, sys te mic cleara nce of mi daz ola m was 1. 7 ti mes
hi g her [ 0. 6 5 ( 7 %) vs 0. 3 9 ( 1 1 %) L/ mi n, mea n ± R S E ( p< 0. 0 1), res pecti vel y] i n 1 8 m or bi dl y  
o bese i n di vi d uals w h o l ost a mea n of 4 4. 5 ± 1 0. 2 k g b o d y  wei g ht.4 1 T he a ut h ors s u g geste d 
t hat t he o bser ve d i ncrease i n mi daz ola m cleara nce was p ote ntiall y  d ue t o i ncrease d C Y P 3 A 
acti vit y f oll owi n g wei g ht l oss.
T o t hat e n d , i n vitr o C Y P e nz y me acti vit y  d o w n-re g ulati o n f or a n o vel G L P - 1 Ra/ gl uca g o n 
c o-a g o nist di d n ot tra nslate t o cli nical D DIs. 4 2 B ase d o n i n vitr o data a n d P B P K m o deli n g, a 
2. 4 -f ol d i ncrease i n mi daz ola m A U C a n d a 1. 6 -f ol d i ncrease i n mi daz ola m C ma x was 
e x pecte d, w hile i n t he cli nic n o c ha n ge was o bser ve d i n A U C a n d Cma x was decrease d b y 
2 1 %. S u bjects als o l ost a c o nsi dera ble a m o u nt of b o d y wei g ht ( ~ 1 0 %) o ver t he c o urse of t he 
st u d y. These data hi g hli g ht t he u ncertai nt y f or tra nslati o n of i n vitr o data t o cli nical D DI f or 
t his mec ha nis m, a n d pr o vi de a d diti o nal s u p p or t t hat t he i ncreases i n C Y P 3 A acti vit y 
o bser ve d cli nicall y  wit h t he G LP- 1 Ra/ gl uca g o n c o -a g o nist a n d t he a p pare nt i ncreased 
C Y P 3 A acti vit y  f oll o wi n g wei g ht l oss m a y  be mec ha nis m -relate d; ie, d ue t o wei g ht l oss
itself, alterati o ns i n i nfla m mat or y stat us, G L P -1 R p har mac ol o g y , etc.  
T he o bjecti ve of C o h ort 2 is t o test t he h yp ot hesis t hat decreases i n b o d y  wei g ht lesse n t he
infla m mat or y  b ur de n of o besit y, a n d t heref ore, atte n uate s o me of t he i n hi bit or y i m pact of 
o besit y o n C Y P 3 A acti vit y.  T his res ults i n “ n or malizati o n” of C Y P 3 A acti vit y, w hic h 
ma nifests as e nz y me i n d ucti o n as e vi de nce d b y t he af ore me nti o ne d decreases i n mi daz ola m 
e x p os ure .
O nce wee kl y se ma gl uti de a d mi nistrati o n u p t o t he ma xi m u m a p pr o ve d d ose of 2. 4 m g  is 
e x pecte d t o res ult i n c o nsi dera ble wei g ht l oss. As se ma gl uti de is a p e pti de i nte n de d f or 
s u bc uta ne o us i njecti o n, C Y P -me diate d D DIs are n ot e x pecte d ; in vitr o st u dies ha ve s h o w n 
ver y  l o w p ote ntial f or se ma gl uti de t o i n hi bit or i n d uce C Y P e nz ymes. 1 6 ,1 7 T heref ore , a n y
decrease o bser ve d f or mi daz ola m s y tste mic e xp os ure s i n C o h ort 2 w o ul d li kel y be 
mec ha nis m base d; ie, d ue t o wei g ht l oss, alterati o ns i n i nfla m mat or y  stat us, G LP- 1 Ra
p har mac ol o g y , etc.  Base d o n hist orical wei g ht l oss data f or P F - 0 7 0 8 1 5 3 2 i n t he 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 6
m ulti ple -asce n di n g d ose st u d y ( C 39 9 1 0 0 2), P F -0 7 0 8 1 5 3 2 is e x pecte d t o res ult i n wei g ht l oss 
i n t he c urre nt st u dy , t h us, all o wi n g f or a c o m paris o n of t he i m pact of wei g ht l oss o n 
mi daz ola m P K bet wee n C o h orts 1 a n d 2.  
F oll o wi n g assess me nt of t he D DI bet wee n se ma gl uti de a n d mi daz ola m, t he a d mi nistr ati o n of 
se ma gl uti de will be disc o nti n ue d f or a 2- wee k peri o d, after w hic h a n a d diti o nal si n gle d ose 
of mi daz ola m will be a d mi nistere d t o assess a n y i m pact of disc o nti n uati o n of se ma gl uti de 
a d mi nistrati o n o n mi daz ola m p har mac o ki netics.  If i n d ucti o n of C Y P3 A acti vit y is o bser ve d
(as deter mi ne d by mi daz ola m P K d uri n g c oa d mi nistrati o n of se ma gl uti de ), t he 
disc o nti n uati o n of se ma gl uti de is n ot e x pecte d t o ha ve a n i m pact o n s u bse q ue nt mi daz ola m 
P K , a n d w o ul d m ost li kel y be attri b ute d t o wei g ht l oss a n d t he atte n uati o n of circ ulati n g 
i nfla m mat or y mar kers t hat i m pact C Y P 3 A acti vit y. 
Mi daz ola m will be use d as a “se nsiti ve s u bstrate” of C Y P 3 A i n C o h ort 2 t o assess t he i m pact 
of m ulti ple - d ose se ma gl uti de a d mi nistrati o n o n t he P K of b ot h mi daz ola m a n d its 1-h y dr o x y  
meta b olite.  T o f urt her i n vesti gate t he mec ha nis m of t his i nteracti o n, plas ma 
4- -h y dr o x yc h olester ol/c h olester ol a n d 
 sa m ples, use d as e n d o ge n o us pr o bes f or C Y P 3 A 
i n d ucti o n, will be c ollecte d a n d a nal yze d if c ha n ges are o bser ve d i n mi daz ola m e x p os ure s. 
S e ma gl uti de will be a d mi nistere d as i nstr ucte d i n t he res pecti ve a p pr o ve d U S PIs; ie, o nce 
wee kl y s u bc uta ne o us i njecti o ns at t he 0. 2 5 m g, 0. 5 m g, 1. 0 m g , 1. 7 m g a n d 2. 4 m g d oses ,
eac h f or 4 wee ks. 1 6 ,1 7 O ne a d diti o nal 2. 4 m g d ose of se ma gl uti de will be a d mi nistere d t o 
e ns ure attai n me nt of P K stea d y -state (ter mi nal half-life is a p pr oxi matel y  1 wee k) pri or t o 
a d mi nistrati o n of t he sec o n d mi daz ola m d ose i n Peri o d 3 ( Secti o n 6. 1. 1 ). T his will e na ble 
a n y i nteracti o n t hat is prese nt t o be assesse d u n der c o n diti o ns t hat are e x pecte d t o i ncrease 
t he p ote ntial f or ma xi mal C Y P 3 A i n d ucti o n at t he 2. 4 m g se ma gl uti de d ose , s h o ul d t his 
occ ur . 
4. 2. 3. S afet y Assess me nts ( C o h orts 1 a n d 2)
Cli nical la b orat or y  tests, assess me nts of vital si g ns, b o d y wei g ht, 1 2- lea d E C Gs, p h ysical 
e xa mi nati o ns, a n d A E m o nit ori n g will pr o vi de data t o e val uate t he safet y a n d t olera bilit y of 
P F -0 7 0 8 1 5 3 2.  Vital si g ns a n d 1 2-lea d E C Gs will be m o nit ore d at t he S cree ni n g a n d st u d y 
disc har ge visits, a n d as necessar y at t he discreti o n of t he i n vesti gat or. B o d y  wei g ht will be 
meas ure d at ti me p oi nts i n t he S o A , as G LP- 1 R a g o nists ha ve bee n s h o w n t o decrease f o o d 
i nta ke a n d b o dy wei g ht.  C O VI D - 1 9 s pecific assess me nts ha ve bee n i nc or p orate d t o 
mi ni mize t he ris ks of C O VI D -1 9 relate d c o m plicati o ns t o partici pa nts a n d t he st u d y  site 
pers o n nel.
As part of t he cli nical safet y  la b orat or y tests, fasti n g bl o o d gl uc ose a n d H b A 1c will be use d 
t o assess c han ges i n gl yc e mic para meters i n t his st u d y  p o p ulati o n.  I n a d diti o n, calcit o ni n, 
a m ylase, a n d li pase will be assesse d, as t hese la b orat or y para meters ha ve bee n s h o w n t o 
i ncrease wit h mar kete d G LP- 1 R a g o nists. 1 6 ,1 7,4 3 ,4 4 ,4 5 ,4 6 T S H, free T 4, li pi ds, a n d T B A will
als o be assesse d, base d o n n o na d verse fi n di n gs i n t he n o ncli nical st u dies wit h P F -0 7 0 8 1 5 3 2 .  
Assess me nt of SI B b y  C-S S R S 4 7 a n d P H Q- 9 4 8 will als o be perf or me d base d o n t he p ote ntial 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 7
ris k relate d t o t he pr o d uct la beli n g f or t he i njecta ble G LP- 1 R a g o nist s lira gl uti de a n d 
se ma gl uti de i n l o n g-ter m st u dies of patie nts wit h B MI ≥3 0 k g/ m 2.1 6 ,1 7 ,4 4 ,4 5
W hile G L P- 1 R a g o nists t y picall y  are n ot ass ociate d wit h h yp o gl yce mia u nless 
c oa d mi nistere d wit h a nti-dia betic a ge nts t hat ca n ca use h y p o gl yce mia (s uc h as i ns uli n or 
s ulf o n yl ureas), bl o o d gl uc ose c o nce ntrati o ns will be m o nit ore d t hr o u g h o ut t he st u d y via 
la b orat or y assess me nts, a n d m o nit ori n g of sy m pt o matic H A Es will be perf o r me d.  I n 
a d diti o n, all partici pa nts will be i nstr ucte d re gar di n g t he s y m pt o ms ass ociate d wit h, a n d 
ma na ge me nt of, h y p o gl yce mia, w hic h will per mit t he m o nit ori n g of s y m pt o matic H A Es.
W O C B P
ma y  be e nr olle d gi ve n t he a vaila bilit y of e m br yo fetal de vel o p me nta l t o xicit y 
st u dies wit h P F - 0 7 0 8 1 5 3 2.  H o we ver, as mar kete d G LP -1 R a g o nists are liste d as 
c o ntrai n dicate d i n pre g na nc y, t he use of a hi g hly effecti ve met h o d of n o n h or m o nal 
c o ntrace pti o n is re q uire d a n d meas ures will be ta ke n t o li mit t he ris k of pre g na nc y  in t he 
W O C B P
p o p ulati o n e nr olle d (see S o A a n d A p pe n di x 4 ).
4. 2. 4. Di versit y of St u d y P o p ul ati o n  
N ot a p plica ble.
4. 2. 5. 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 0 8 1 5 3 2, b ut 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 c o m plete d n o ncli nical e m br yo- fetal de vel o p me ntal 
st u dies.  H o we ver, t he use of a hi g hly effecti ve met h o d of n o n h or m o nal c o ntrace pti o n is 
re q uire d f or b ot h c o h orts i n t his st u d y (see A p pe n di x 4 ).  
4. 2. 6. C ollecti o n of Ret ai ne d Rese arc h S a m ples
 
4. 3. J ustific ati o n f or D ose
P F -0 7 0 8 1 5 3 2 :
T he D DI will be assesse d at 2 p har mac o ki netic stea d y-state P F - 0 7 0 8 1 5 3 2 d ose le vels, 
8 0 m g Q D a n d 26 0 m g Q D .  T he se d ose s re prese nt a p ote ntial t hera pe utic d ose f or T 2 D M,
a n d t he hi g hest d ose bei n g as sesse d i n t he P hase 2 st u d y ( C 3 9 9 1 0 0 4) f or T 2 D M a n d o besit y , 
res pecti vely. E x p os ure mar gi ns f or P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D are gi ve n i n Secti o n 2. 2. 3 . 
T he titrati o n t o P F - 0 7 0 8 1 5 3 2 80 m g Q D is pla n ne d t o occ ur o ver a n a p pr o xi matel y 2 8-d a y  
peri o d i n i ncre me nts of 2 0 m g Q D e ver y 7 d a y s, a n d fr o m 8 0 m g Q D t o 26 0 m g Q D o ver 
9 wee ks , i n i ncre me nts of 2 0 m g e ver y  7 da y s (Secti o n 6. 1. 1 , Ta ble 8 a n d Ta ble 9 ). T itrati o n 
i ncre me nts as s h ort as 1- 2 da y s ha ve bee n a d mi nistere d pre vi o usl y i n S t u d y C 39 9 1 0 0 2 a n d 
were s ufficie ntl y t olerate d.   Base d o n e mer gi n g data fr o m ot her cli nical st u dies t hat ma y 
bec o me a vaila ble d uri n g t he c o n d uct of t his st u d y , t he titrati o n rate, i ncre me ntal i ncreases i n 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 8
d ose, a n d/ or t he P F -0 7 0 8 1 5 3 2 d oses at w hic h mi daz ola m , o me praz ole or t he O C P K 
i nteracti o ns are e val uate d ma y be a dj uste d.  
Mi d az ol a m:
Mi daz ola m has bee n a d mi nistere d at d oses of 2 -1 5 m g t o assess C Y P 3 A 4/ 5 D DI s a n d wa s 
ge nerall y well t olerate d.  T he si n gle, oral 2 m g  d ose of mi daz ola m i n t his st u d y s h o ul d all o w 
f or a de q uate q ua ntificati o n of mi daz ola m a n d its 1-h y dr o x y meta b olite i n plas ma f or 2 4 h o urs 
a n d is e x pecte d t o be well- t olerate d.  A d diti o nall y , as mi daz ola m a n d o me praz ole are t o be 
a d mi nistere d si m ulta ne o usl y ( C o h ort 1 o nly) , mi daz ola m d oses greater t ha n 2 m g ha ve n ot 
bee n vali date d f or c oa d mi nistrati o n wit h o me praz ole. 1 8 ,1 9
O me pr az ole :
T he safet y data descri be d i n t he U S PI1 4 f or o me praz ole m o n ot hera py reflects e x p os ure t o 
P RI L O S E C Dela y e d-Release Ca ps ules i n 3 0 9 6 patie nts fr o m w orl d wi de cli nical trials 
( 4 6 5 patie nts fr o m U S st u dies a n d 2, 6 3 1 patie nts fr o m i nter nati o nal st u dies). I n dicati o ns 
cli nicall y st u die d i n U S trials i ncl u de d d u o de nal ulcer, resista nt ulcer, a n d 
Z olli n ger -Ellis o n s y n dr o me. T he m ost c o m m o n a d verse reacti o ns re p orte d (ie, wit h a n 
i nci de nce rate ≥2 %) fr o m P RI L O S E C -treate d patie nts e nr olle d i n t hese st u dies i ncl u de d 
hea dac he ( 6. 9 %), a b d o mi nal pai n ( 5. 2 %), na usea ( 4. 0 %), diarr hea ( 3. 7 %), v o miti n g 
( 3. 2 %), a n d flat ule nce ( 2. 7 %). 
T he d ose ra n ge a n d rec o m me n de d starti n g d oses f or o me praz ole i n cli nical practice is 2 0 t o 
6 0 m g o nce dail y f or u p t o 8 wee ks i n a d ults de pe n di n g o n t he c o n diti o n bei n g treate d. 1 4 I n
patie nts wit h Z olli n ger -Ellis o n s y n dr o me, d oses of u p t o 2 4 0 m g/ da y m a y  be re q uire d. 
Base d o n i n vitr o data, P F - 0 7 0 8 1 5 3 2 is a m o derate ti me-de pe n de nt i n hi bit or of C Y P 2 C 1 9
a n d c o ul d p ote ntiall y i ncrease o me praz ole e x p os ure 2. 2- t o 3. 4 -f ol d at a 2 6 0 m g d ose.  
T heref ore , a 2 0 m g si n gle d ose of o me praz ole was selecte d f or t his st u d y.  Gi ve n t h e 
esta blis he d safety a n d t olera bilit y f or o me praz ole wit h m ulti ple - d ose a d mi nistrati o n u p t o 
2 4 0 m g/ da y , a 2 0 m g si n gle d ose is e x pecte d t o be well t olerate d e ve n if s yste mic e x p os ures 
i ncrease u p t o 5-f ol d as a res ult of c oa d mi nistrati o n wit h P F - 0 7 0 8 1 5 3 2. A d diti o nall y , as 
mi daz ola m a n d o me praz ole are t o be a d mi nistere d si m ulta ne o usl y ( C o h ort 1 o nl y), 
o me praz ole d oses greater t ha n 2 0 m g ha ve n ot bee n vali date d f or c oa d mi nistrati o n wit h 
mi daz ola m.
1 8 ,1 9
L E/ E E :
T he O C selecte d f or t his st u d y  c o ntai ns a fi xe d d ose of 0. 1 5 m g L E a n d 0. 0 3 m g E E .  The 
a m o u nts of estr o ge n a n d pr o gesti n i n t his pre parati o n are c o m para ble t o t h ose f o u n d i n ma n y 
of t he c o m m o nl y  prescri b e d O Cs a n d ha ve bee n use d i n a n u m ber of p u blis he d O C D DI
st u dies.4 9 ,5 0
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 9
S e m a gl uti de:
S u bc uta ne o us s e ma gl uti de will be titrate d u p t o 2. 4 m g wee kl y as t his is t he ma xi m u m 
a p pr o ve d d ose f or wei g ht l oss a n d was s h o w n t o be safe a n d well -t olerate d i n cli nical 
trials.1 6 ,1 7
4. 4. E n d of St u d y Defi niti o n
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  if he/s he has c o m plete d all p hases of 
t he st u d y, i ncl u di n g t he F/ U c o ntact visit, a p pr o xi matel y  2 8 t o 3 5 d a y s p ost last d ose of st u d y 
i nter ve nti 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 visit ( F/ U c o ntact) of t he last partici pa nt 
i n t he st u d y.
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nt s are e nr olle d. 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 partici pa nt is s uita ble f or t his 
pr ot oc ol .
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria , als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
Partic i pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nly if all of t he f oll o wi n g criteria a p pl y:
A ge a n d Se x :
1.
Ot her wise h ealt h y fe male partici pa nts m ust be at least 1 8 y ears of a ge at t he ti me of 
si g ni n g t he I C D ( healt hy is defi ne d as n o cli nicall y rele va nt a b n or malities i de ntifie d 
b y  a detaile d me dical hist or y , p h ysical e xa mi nati o n, i ncl u di n g bl o o d press ure a n d 
p ulse rate meas ure me nt, sta n dar d 1 2 -lea d E C G a n d cli nical la b orat or y tests).

W o me n ca n be of c hil d -beari n g p ote ntial, b ut ca n n ot be pre g na nt, breastfee di n g, 
or pla n ni n g t o bec o me pre g na nt w hile partici pati n g i n t he st u d y a n d ma y n ot be 
ta ki n g eit her oral c o ntrace pti ves or n o n - oral h or m o nal c o ntrace pti ves. 

Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or fe male partici pa nts
(Secti o n 1 0. 4. 2 ).
T y pe of P artici p a nt a n d Dise ase C h ar acteristics:
2.
Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt 
pla n, la b orat or y  tests, lifest yle c o nsi derati o ns, a n d other st u d y  pr oce d ures.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 0
Wei g ht:
3.
B MI : ≥3 0 . 0 k g/ m2 a n d n ot m ore t ha n 4 5. 4 k g/ m 2 at Scree ni n g
4.
Sta ble b o d y  wei g ht, defi ne d as < 5 k g c ha n ge ( per partici pa nt re p ort) f or 9 0 da y s 
bef ore Scree ni n g. 
I nf or me d C o nse nt:
5.
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 nclu di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).
2.
A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, pri or bariatric s ur ger y, 
gastrect o m y, or a n y area of i ntesti nal resecti o n, acti ve i nfla m mat or y  b o wel disease or 
pa ncreatic i ns ufficie nc y ). 
3.
Ot her me dical or ps y c hiatric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past year) or 
acti ve s uici dal i deati o n/ be ha vi or or la b orat or y  a b n or malit y t hat ma y i ncrease t he ris k 
of st u d y partici pati o n or, i n t he i n vesti gat o r’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.
4.
K n o w n i nt olera nce or h y perse nsiti vit y  t o G L P-1 R a g o nists.
5.
K n o w n h y perse nsiti vit y  t o mi daz ola m , o me praz ole, L E , E E , or se ma gl uti de.
6.
Dia g n osis of t y p e 1 or t y pe 2 dia betes mellit us or sec o n dar y f or ms of dia betes at 
scree ni n g.  N ote: w o me n wit h pri or dia g n oses of gestati o nal dia betes d uri n g 
pre g n a ncy o n ly are eli gi ble if t he y meet t he ot her eli gi bilit y criteria.
7.
Hist or y  of my o car dial i nfarcti o n, u nsta ble a n gi na, arterial re vasc ularizati o n, str o ke,
Ne w Y or k Ass ociati o n F u ncti o nal Class II- I V heart fail ure, or tra nsie nt isc he mic 
attac k wit hi n 6 m o nt hs of Scree ni n g.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 1
8.
A n y mali g na nc y  n ot c o nsi dere d c ure d (e xce pt basal cell carci n o ma a n d s q uam o us cell
carci n o ma of t he s ki n); a st u d y partici pa nt is c o nsi dere d c ure d if t here has bee n n o
e vi de nce of ca ncer rec urre nce i n t he pre vi o us 5 ye ars (fr o m Scree ni n g).
9.
Pers o nal or fa mil y hist or y of me d ullar y  t h yr oi d carci n o ma ( M T C) or m ulti ple
e n d ocri ne ne o plasia s y n dr o me t y pe 2 ( M E N 2), or st u d y  partici pa nts wit h s us pecte d
M T C per t he i n vesti gat or’s j u d g me nt.
1 0. Ac ute pa ncreatitis or hist or y  of c hr o nic pa ncreatitis. S y m pt o matic gall bla d der 
disease.
1 1. Me dical hist or y  or c haracteristics s u g gesti ve of ge netic or s yn dr o mic o besit y  or
o besit y  i n d uce d by ot her e n d ocri n ol o gical dis or ders (e g, C us hi n g S y n dr o me).
1 2. Hist or y  of maj or de pressi ve dis or der or hist or y of ot her se vere psyc hiatric dis or ders
(e g, sc hiz o p hre nia or bi p olar dis or der) wit hi n t he last 2 years fr o m scree ni n g.
1 3. K n o w n me dical hist or y  of acti ve li ver disease ( ot her t ha n n o n-alc o h olic he patic
steat osis), i ncl u di n g c hr o nic acti ve he patitis B or C, pri mar y biliar y cirr h osis,
alc o h olic li ver disease, pri mar y  scler osi n g c h ola n gitis, a ut oi m m u ne he patitis, o verla p
s yn dr o me, or pri or k n o w n dr u g -i n d uce d li ver i nj ur y.
1 4. Hist or y  of HI V i nfecti o n.
1 5. A n y  lifeti me hist or y of a s uici de atte m pt.
Pri or/ C o nc o mit a nt T her a p y:
1 6. 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.  ( Refer t o Secti o n 6. 9 C o nc o mita nt T hera p y f or a d diti o nal details).
1 7. Use of a n y t he me dicati o ns t hat are m o derate or str o n g C Y P 3 A 4/ 5 a n d/or C Y P 2 C 1 9 
i n hi bit ors wit hi n 2 8 da ys or 5 half-li ves ( w hic he ver is l o n ger) or mo derate or str o n g 
C Y P 3 A a n d/ or C Y P 2 C 1 9 i n d ucers wit hi n 1 4 da ys or 5 half -li ves ( w hic he ver is 
l o n ger) pri or t o t he first d ose of st u d y i nter ve nti o n ( Refer t o Secti o n 6. 9 f or a d diti o nal 
details). 
1 8. C urre nt use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) or t h ose u n willi n g/ u na ble t o 
use a per mitte d c o nc o mita nt me dicati o n(s ). Refer t o Secti o n 6. 9 C o nc o mita nt
T hera p y .
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
1 9. Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal dr u g wit hi n 3 0 d a 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). 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 2
2 0. Pre vi o us a d mi nistrati o n wit h a G L P- 1 R a g o nist wit hi n 9 0 da y s prece di n g t he first 
d ose of st u d y  i nter ve nti on use d i n t his st u d y .  
2 1. K n o w n pri or partici pati o n i n a trial i n v ol vi n g P F - 0 7 0 8 1 5 3 2 u nless place b o treat me nt 
was recei ve d .
Di a g n ostic Assess me nts ( at Scree ni n g u nless i n dic ate d):
2 2. A P H Q - 9 sc ore ≥1 5 o btai ne d at Scree ni n g or Da y  -1 i n St u d y .
2 3. Res p o nse of “ y es” t o q uesti o n 4 or 5, or o n a n y s uici dal be ha vi oral q uesti o n o n t he 
C- S S R S at Scree ni n g or Da y  -1 i n St u d y .
2 4. A p ositi ve uri ne dr u g test. 
2 5. 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 oll o wi n g at 
least 5 mi n utes of s u pi ne rest.  B P s h o ul d be meas ure d i n tri plicate 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 .  N ote: At 
S cree ni n g, t he partici pa nt’s ar m circ u mfere nce s h o ul d be meas ure d (e g, usi n g a 
fle xi ble a nt hr o p o metric ta pe) at t he mi d p oint of t he le n gt h of t he u p per ar m, a n d t he 
a p pr o priate c uff selecte d a n d use d t hr o u g h o ut t he st u d y .
2 6. Scree ni n g 1 2 -lea d E C G t hat de m o nstrates cli nicall y rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F i n ter val 
> 4 5 0 msec, c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate a ge m y ocar dial 
i nfarcti o n, S T- T i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d- or 
t hir d-de gree A V bl oc k, or seri o us bra d ya rr hyt h mias or tac h y arr h yt h mias).  
If Q Tc F e xcee ds 4 5 0 msec, or Q R S e xcee ds 1 2 0 msec, t he E C G 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 Q Tc F or Q R S 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 .  C o m p uter i nter prete d E C Gs s h o ul d be 
o verrea d b y a p h ys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g partici pa nts.
2 7. 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 
S cree ni n g, as assesse d b y t he st u d y  s pecific la b orat or y a n d c o nfir me d by a si n gle 
re peat test, if dee me d necessar y:

H b A 1c ≥6. 5 %.

A S T or A L T le vel ≥1. 5 x U L N.

T otal bilir u bi n le vel ≥1. 5 x U L N; partici pa nts wit h a hist or y  of Gil bert's sy n dr o me 
ma y  ha ve 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.

T S H > 1. 5 x U L N or < L L N.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 3

Ser u m calcit o ni n > U L N.

A m y lase or li pase > U L N.

Fasti n g bl o o d gl uc ose ≥1 2 6 m g/ d L. 

Fasti n g C -pe pti de < 0. 8 n g/ m L.

e G F R < 7 5 m L / mi n/ 1. 7 3 m2 as calc ulate d b y t he C hr o nic Ki d ne y  Disease 
E pi de mi ol o g y  C olla b orati o n (C K D -E PI ) e q uati o n.

P ositi ve testi n g f or HI V, H Bs A g , or H C V A b.  St u d y partici pa nts p ositi ve f or 
H C V A b are t o be e xcl u de d u nless k n o w n t o ha ve bee n treate d wit h a k n o w n 
c urati ve t hera p y a n d ne gati ve f or H C V R N A.  He patitis B vacci nati o n is all o we d.

A p ositi ve S A R S -C o V - 2 test.
Ot her E xcl usi o ns : at Scree ni n g u nless i n dic ate d
2 8. Partici pati o n i n a f or mal wei g ht re d ucti o n pr o gra m (e g, Wei g ht Watc hers) wit hi n 
9 0 da y s pri or t o Scree ni n g.
2 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) o f wi ne).
3 0. C urre nt 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 per da y.
3 1. K n o w n or s us pecte d illicit dr u g use.
3 2. Bl o o d d o nati o n (e xcl u di n g plas ma d o nati o ns) of a p pr o xi matel y  1 pi nt ( 5 0 0 m L ) or 
m ore wit hi n 6 0 da y s pri or t o d osi n g ra n d o mizati o n ( Da y-1). 
3 3. Hist or y  of se nsiti vit y t o he pari n or he pari n i n d uce d t hr o m b oc yt o pe nia if He p l oc k is 
use d f or I V bl o o d dra w.
3 4. U n willi n g or u na ble t o c o m pl y  wit h t he criteria i n t he Li fest yle C o nsi derati o ns
secti o n of t his pr ot oc ol.
3 5. I n vesti gat or site staff or Pfizer e m pl o yees directl y i n v ol ve d i n t he c o n d uct of t he 
st u d y, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d t heir res pecti ve fa mil y 
me m bers. 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 4
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.
Me als a n d Diet ar y Restricti o ns

Partici pa nts m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt water) f or at least 8 h o urs 
pri or t o a n y m or ni n g pre d ose P K e val uati o ns (s pecifie d ti mes i n Peri o ds 1 - 9 i n 
C o h ort 1 a n d Peri o ds 1- 4 i n C o h ort 2 ).  O n da y s wit h o ut P K e val uati o ns, partici pa nts 
m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt water) f or at least 4 h o urs pri or t o a n y  
safety la b orat or y  e val uati o ns (at least 1 2 h o urs if li pi ds are t o be e val uate d). 

Water ma y  be c o ns u me d as desire d (a d li bit u m).

C o h ort 1 - Partici pa nts s h o ul d be gi n c o ns u m pti o n of a sta n dar d brea kfast ( m or ni n g)
a p pr o xi matel y 3 0 mi n utes pri or t o d osi n g.  T he brea kfast meal will be c o ns u me d o ver 
a p pr o xi matel y a 2 0-mi n ute peri o d, wit h t he st u d y  i nter ve nti o n (P F -0 7 0 8 1 5 3 2 ) 
a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes of c o m pleti o n of t he meal.  
Partici pa nts will be e nc o ura ge d t o c o ns u me t he e ntire meal.
P F - 0 7 0 8 1 5 3 2 will be a d mi nistere d first a n d t he si n gle d ose of mi daz ola m a n d
o me praz ole or t he O C will be a d mi nistere d wit hi n 5 mi n utes of P F -0 7 0 8 1 5 3 2 f or t he 
peri o ds i n w hic h mi daz ola m a n d o me praz ole or t he O C are c oa d mi nistere d wit h 
P F - 0 7 0 8 1 5 3 2. 
Mi daz ola m a n d o me praz ole,
or t he O C, w he n a d mi nistere d al o ne , will be gi ve n 
wit hi n a p pr o xi matel y  1 0 mi n utes of c o m pleti o n of t he m or ni n g meal. 
C o h ort 2 – Peri o d 1 : O n t he i n-patie nt D DI assess me nt da y , p artici pa nts s h o ul d be gi n 
c o ns u m pti o n of a sta n dar d brea kfast ( m or ni n g) a p pr o xi matel y  3 0 mi n utes pri or t o 
d osi n g.  T he brea kfast meal will be c o ns u me d o ver a n a p pr o xi mate 2 0 -mi n ute peri o d, 
wit h t he st u d y  i nter ve nti o n (se ma gl uti de) a d mi nistere d wit hi n a p pr o xi matel y 
1 0 mi n utes of c o m pleti o n of t he meal, f oll o we d wit hi n 5 mi n utes b y  t he si n gle d ose 
of mi daz ola m.   Partici pa nts will be e nc o ura ge d t o c o ns u me t he e ntire meal.
Peri o d 2 : O n o ut-patie nt da y s, partici pa nts ma y c o ns u me meals at a n y ti me.  
Peri o d 3 : O n t he i n-patie nt D DI assess me nt da y , partici pa nts s h o ul d be gi n 
c o ns u m pti o n of a sta n dar d brea kfast ( m or ni n g) a p pr o xi matel y  3 0 mi n utes pri or t o 
d osi n g.  T he brea kfast meal will be c o ns u me d o ver a n a p pr o xi mate 2 0 -mi n ute peri o d , 
wit h t he st u d y  i nter ve nti o n (se ma gl uti de) a d mi nistere d wit hi n a p pr o xi matel y 
1 0 mi n utes of c o m pleti o n of t he meal, f oll o we d wit hi n 5 mi n utes b y  t he si n gle d ose 
of mi daz ola m. Partici pa nts will be e nc o ura ge d t o c o ns u me t he e ntire meal.

N o ncaffei nate d dri n ks (e xce pt re d wi ne, gra pefr uit or gra pefr uit- relate d citr us fr uit 
j uices [ e g, Se ville ora n ges, p o mel os]) 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.  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 5

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 wit h st u d y  i nter ve nti o n 
(P F - 0 7 0 8 1 5 3 2 or se ma gl uti de).  T his a p plies t o mi daz ola m , o me praz ole a n d t he O C
als o.

Di n ner will be pr o vi de d a p pr o xi matel y  1 0 h o urs after d osi n g wit h st u d y i nter ve nti o n. 
T his a p plies t o mi daz ola m, o me praz ole a n d t he O C als o.

A n e ve ni n g s nac k ma y  be per mitte d.

C o h ort 1: 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 a n d j uices (e g, Se ville ora n ges, p o mel os) fr o m 7 da ys pri or t o 
Peri o d 1 Da y 1 u ntil c ollecti o n of t he fi nal P K bl o o d sa m ple i n Peri o d 9, Da y 2 .
Partici p a nts are als o e x pecte d t o refrai n fr o m c o ns u mi n g t hese pr o d ucts d uri n g t he 
2 -wee k o ut -patie nt p orti o n of t he st u d y f oll o wi n g t he O C D DI assess me nt i n 
Peri o d 8 ; ie, bet wee n Peri o d 8, Da y 6 a n d Peri o d 9, Da y  1.

C o h ort 2: 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 a n d j uices (e g, Se ville ora n ges, p o mel os) fr o m 7 da ys pri or t o 
a d missi o n t o t he cli nical site o n Da y  1 of Peri o d s 1 a n d 3 a n d d uri n g all i n-patie nt 
sta ys. Partici pa nts are als o e x pecte d t o refrai n fr o m c o ns u mi n g t hese pr o d ucts d uri n g 
t he 2- wee k o ut -patie nt p orti o n of t he st u d y f oll o wi n g t he mi daz ola m D DI assess me nt 
i n Peri o d 3; ie, bet wee n Peri o d 3 , Da y 2 a n d Peri o d 4 , Da y 1.

W hile partici pa nts are c o nfi ne d, t heir t otal dail y  n utriti o nal co m p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat, a n d 1 5 % pr otei n.  T he dail y cal oric i nta ke 
per partici pa nt s h o ul d n ot e xcee d a p pr o xi matel y  3 2 0 0 kcal.
5. 3. 2. C affei ne, Alc o h ol, a n d T o b acc o

T o bacc o or nic oti ne use ma y  be all o we d acc or di n g t o C R U practices.  T o bacc o or 
nic oti ne use will n ot be per mitte d d uri n g fre q ue nt sa m pli n g pr oce d ures a n d will n ot 
be per mitte d wit hi n 2 h o urs pri or t o a n y vital si g n or E C G assess me nts.  T o bacc o or 
nic oti ne use will als o n ot be per mitte d 2 h o urs bef ore a n d 2 h o urs f ol l o wi n g a ny d ose 
of st u d y  i nter ve nti o n.  

Caffei ne c o ntai ni n g pr o d ucts will be per mitte d d uri n g t he st u d y wit h t he f oll o wi n g 
restricti o ns: caffei ne c o ntai ni n g pr o d ucts ma y n ot be c o ns u me d wit hi n 1 h o ur pri or t o 
meas uri n g vital si g ns a n d E C Gs.

Partici pa nts w ill a bstai n fr o m alc o h ol f or 2 4 h o urs pri or 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 i n C o h ort 1, 
Peri o d 9 , D a y 2 .  Partici pa nts will a bstai n fr o m alc o h ol f or 2 4 h o urs pri or 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 mi daz ola m P K sa m ple i n C o h ort 2 ; Peri o d 2 Da y  1, Peri o d 3 Da y 2, a n d 
Peri o d 4 D a y 2.  Partici pa nts ma y  u n der g o a n alc o h ol breat h test or bl o o d alc o h ol test 
at t he discreti o n of t he i n vesti gat or.  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 6
5. 3. 3. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea v y lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c oll ecti o n f or cli nical 
la b orat or y tests.  Wal ki n g at a n or mal pace will be per mitte d.

I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, partici pa nts will be 
re q uire d t o refrai n fr o m l yi n g d o w n f or 4 h o urs after d osi n g i n t he m or ni n g o n da ys of 
p ost -d ose P K sa m ple c ollecti o ns (e xce pt if re q uire d f or B P, p ulse rate, a n d E C G 
meas ure m e nts).
5. 3. 4. C o ntr ace pti o n
W O C B P
O nl y  - T he i n vesti gat or or his or her desi g nee, i n c o ns ultati o n wit h t he partici pa nt, 
will c o nfir m t hat t he partici pa nt has selecte d a n a p pr o priate met h o d of n o n h or m o nal 
c o ntrace pti o n f or t he i n di vi d ual partici pa nt a n d his or her part ner(s) fr o m t he per mitte d list of 
n o n h or m o nal c o ntrace pti o n met h o ds (see A p pe n di x 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.  At ti me p oi nts i n dicate d i n t he sc he d ule 
of acti vities ( 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 hl y effecti ve n o n h or m o nal c o ntrace pti o n c o nsiste ntl y a n d c orrectly a n d d oc u me nt t he 
c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart ( partici pa nts nee d t o 
affir m t heir c o nsiste nt a n d c orrect use of at least 1 of t he selecte d me t h o ds of n o n h or m o nal 
c o ntrace pti o n) c o nsi deri n g t hat t heir ris k f or pre g na nc y  ma y ha ve c ha n ge d si nce t he last visit.  
I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he partici pa nt t o call i m me diatel y if t he 
selecte d n o n h or m o nal c o ntrace pti o n met h o d is disc o nti n ue d or if pre g na nc y  is k n o w n or 
s us pecte d i n t he partici pa nt or part ner .
5. 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 d ose 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 t o t he cli nical data base.
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 wit hi n t he 2 8 -d a y  scree ni n g 
wi n d o w ma y  be re-scree ne d. I n t his sit uati o n, all scree ni n g pr oce d ures m ust be re peate d, a n d 
t he partici pa nt assi g ne d a ne w 8-di git S SI D n u m ber.  T his criteri o n w o ul d als o a p pl y  t o 
partici pa nts w h o scree ne d f or t his st u d y  m ore t ha n 2 8 da y s pri or t o d osi n g.
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
St u d y  i nter ve nti o n is define d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), 
place b o, me dical de vice(s) , or st u d y pr oce d ure(s) i nte n de d t o be a d mi nistere d t o a st u d y 
partici pa nt acc or di n g t o t he st u d y  pr ot oc ol.
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 0 8 1 5 3 2, mi daz ola m, 
o me praz ole , O C a n d se ma gl uti de.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 7
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
2 0 m g, 6 0 m g, a n d 1 0 0 m g P F - 0 7 0 8 1 5 3 2 oral ta blets will be s u p plie d b y Pfizer t o t he C R U i n 
b ul k al o n g wit h i n di vi d ual d osi n g c o ntai ners, as necessar y, f or u nit d osi n g.
C o m merciall y  a vaila ble s u bc uta ne o us se ma gl uti de ( We g o v y)  will be s u p plie d b y  Pfizer t o 
t he C R U.
C o m merciall y  a vaila ble mi daz ola m oral s yr u p ( 2 m g/ m L) will be s u p plie d b y t he C R U. 
C o m merciall y  a vaila ble oral o me praz ole 2 0 m g  ta blets will be s u p plie d b y t he C R U.
C o m merciall y  a vaila ble oral O C ta blets ( L E 0. 1 5 m g/ E E 0. 0 3 m g ) will be s u p plie d b y t he 
C R U. 
6. 1. 1. A d mi nistr ati o n
C o h ort 1 - Partici pa nts will recei ve P F -0 7 0 8 1 5 3 2 , mi daz ola m a n d o me praz ole, or t he O C as 
a p plica ble per t he S o A at a p pr o xi matel y 0 8 0 0 h o urs (± 2 h o urs).  Details o n meals a n d dietar y  
re q uire me nts a n d acti vit y restricti o ns o n d osi n g da ys are gi ve n i n Secti o n 5. 3 .  
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
wit h t he brea kfast meal at a p pr o xi matel y 0 8 0 0 h o urs ( ± 2 h o urs). I n vesti gat or site pers o n nel 
will a d mi nister P F - 0 7 0 8 1 5 3 2, mi daz ola m a n d o me praz ole, or t he O C d uri n g eac h peri o d (as 
a p plica ble per S o A ) 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 . Partici pa nts will s wall o w t he st u d y i nter ve nti o n w h ole a n d will n ot ma ni p ulate or 
c he w t he st u d y i nter ve nti o n pri or t o s wall o wi n g.   T he st u d y  i nter ve nti o n will be a d mi nistere d 
acc or di n g t o t he I P ma n ual.  
P F - 0 7 0 8 1 5 3 2 m ust be a d mi nistere d wit hi n a p pr o xi matel y  1 0 mi n utes of c o m pleti o n of t he 
m or ni n g meal.  P F -0 7 0 8 1 5 3 2 will be a d mi nistere d first a n d mi daz ola m a n d o me praz ole or 
t he O C will be a d mi nistere d wit hi n 5 mi n utes of P F -0 7 0 8 1 5 3 2 d uri n g t he D DI assess me nt 
peri o ds .
W he n mi daz ola m a n d o me praz ole or t he O C are a d mi nistere d al o ne, t he y m ust be 
a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes of t he c o m pleti o n of t he m or ni n g meal.  
A d mi nistrati o n of st u d y  i nter ve nti o n will occ ur acc or di n g t o t he f oll o wi n g D osi n g Peri o ds 
a n d D osi n g Da ys, als o liste d i n t he S o A a n d Ta ble 8 .
M o dificati o n of d osi n g of P F - 0 7 0 8 1 5 3 2 m a y be per mitte d u p o n S p o ns or a p pr o val o nl y. See
Secti o n 6. 6 . 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 8
T a ble 8 .  
C o h ort 1 D osi n g
St u d y Peri o d
D a ys i n St u d y
Dr u g a n d D os a ge
Peri o d 1, Da y 1
1
S D Mi daz ola m
( 2 m g) + S D O me praz ole ( 2 0 m g)
Peri o d 2, Da ys 1 -5
2 -6
S D O C (L E 0. 1 5 m g/ E E 0. 0 3 m g)
Peri o d 3, Da ys 1 -7
7 -1 3
P F -0 7 0 8 1 5 3 2 2 0 m g Q D
Peri o d 3, Da ys 8 -1 4
1 4 -2 0
P F -0 7 0 8 1 5 3 2 4 0 m g Q D
Peri o d 3, Da ys 1 5 -2 1
2 1 -2 7
P F -0 7 0 8 1 5 3 2 6 0 m g Q D
Peri o d 3, Da ys 2 2 -2 8
2 8 -3 4
P F -0 7 0 8 1 5 3 2 8 0 m g Q D
Peri o d 4, Da y 1
3 5
P F -0 7 0 8 1 5 3 2 8 0 m g Q D + S D Mi daz ola m ( 2 m g) + S D 
O m e praz ole ( 2 0 m g)
Peri o d 5, Da ys 1 -5
3 6 -4 0
P F -0 7 0 8 1 5 3 2 8 0 m g Q D + S D O C ( L E 0. 1 5 m g/ E E 0. 0 3 m g)
Peri o d 6, Da ys 1 -7
4 1 -4 7
P F -0 7 0 8 1 5 3 2 1 0 0 m g Q D
Peri o d 6, Da ys 8 -1 4
4 8 -5 4
P F -0 7 0 8 1 5 3 2 1 2 0 m g Q D
Peri o d 6, Da ys 1 5 -2 1
5 5 -6 1
P F -0 7 0 8 1 5 3 2 1 4 0 m g Q D
Peri o d 6, Da ys 2 2 -2 8
6 2 -6 8
P F -0 7 0 8 1 5 3 2 1 6 0 m g Q D
Peri o d 6, Da ys 2 9 -3 5
6 9 -7 5
P F -0 7 0 8 1 5 3 2 1 8 0 m g Q D
Peri o d 6, Da ys 3 6 -4 2
7 6 -8 2
P F -0 7 0 8 1 5 3 2 2 0 0 m g Q D
Peri o d 6, Da ys 4 3 -4 9
8 3 -8 9
P F -0 7 0 8 1 5 3 2 2 2 0 m g Q D
Peri o d 6, Da ys 5 0 -5 6
9 0 -9 6
P F -0 7 0 8 1 5 3 2 2 4 0 m g Q D
Peri o d 6, Wee k 5 7 -6 3
9 7 -1 0 3
P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D
Peri o d 7, Da y 1
1 0 4
P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D + S D Mi daz ola m ( 2 m g) + S D 
O m e praz ole ( 2 0 m g)
Peri o d 8, Da ys 1 - 6
1 0 5 -1 1 0 *
P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D + S D O C ( L E 0. 1 5 m g/ E E 0. 0 3 m g)
O ut -patie nt
1 1 1 -1 2 4
N o d osi n g
Peri o d 9, Da ys 1 - 2
1 2 5 -1 2 6
S D Mi daz ola m ( 2 m g) o nl y
* T here is n o P F -0 7 0 8 1 5 3 2 a d mi nistrati o n o n Da y 1 1 0 or t hereafter .
C o h ort 2 – Partici pa nts will recei ve se ma gl uti de or mi daz ola m as a p plica ble per t he S o A at 
a p pr o xi matel y 0 8 0 0 h o urs (± 2 h o urs).  Details o n meals a n d dietar y  re q uire me nts a n d acti vit y 
restricti o ns o n d osi n g da ys are gi ve n i n Secti o n 5. 3 .  
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 ( ± 2 h o urs). I n vesti gat or site pers o n nel will a d mi nister (as 
a p plica ble per S o A ) se ma gl uti de as a s u bc uta ne o us i njecti o n d uri n g eac h peri o d .  Mi daz ola m 
will be a d mi nistere 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 . T he st u d y i nter ve nti o n will be a d mi nistere d acc or di n g t o t he I P ma n ual.
Se ma gl uti de m ust be a d mi nistere d o nce wee kl y, prefera bl y i n t he m or ni n g, wit h o ut re gar d t o 
ti mi n g of t he brea kfast meal d uri n g o ut patie nt visits t o t he C R U f or d ose a d mi nistrati o n.  
D uri n g t he D DI assess me nt i n patie nt visit ( Peri o d 3), se ma gl uti de a n d mi da z ola m m ust be 
a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes of c o m pleti o n of t he m or ni n g meal.  
Se ma gl uti de will be a d mi nistere d first, a n d mi daz ola m will be a d mi nistere d wit hi n 5 mi n utes 
of se ma gl uti de.
W he n mi daz ola m is a d mi nistere d al o ne, it m ust be a d mi nistere d wit hi n a p pr o xi matel y  
1 0 mi n utes of t he c o m pleti o n of t he m or ni n g meal.  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 9
A d mi nistrati o n of st u d y  i nter ve nti o n will occ ur acc or di n g t o t he f oll o wi n g D osi n g Peri o ds 
a n d D osi n g Da ys, als o liste d i n t he S o A a n d Ta ble 9 .
M o dificati o n of se ma gl uti de d osi n g m a y  be per mitte d u p o n S p o ns or a p pr o val o nl y . See
Secti o n 6. 6 . 
T a ble 9 .  
C o h ort 2 D osi n g
St u d y Peri o d
D a ys i n St u d y
Dr u g a n d D os a ge
Peri o d 1, Da y 1
1
S D Mi daz ola m
( 2 m g)
Peri o d 2 , Wee ks
1 -4
2 -2 9
S e ma gl uti de 0. 2 5 m g o nce wee kl y
Peri o d 2, Wee ks 5 -8
3 0 -5 7
S e ma gl uti de 0. 5 m g o nce wee kl y
Peri o d 2, Wee ks 9 -1 2
5 8 -8 5
S e ma gl uti de 1. 0 m g o nce wee kl y
Peri o d 2, Wee ks 1 3 -1 6
8 6 -1 1 3
S e ma gl uti de 1. 7 m g o nce wee kl y
Peri o d 2, Wee ks 1 7 -2 1
1 1 4 -1 4 8
S e ma gl uti de 2. 4 m g o nce wee kl y
Peri o d 3 , Da ys 1 -2
1 4 9 -1 5 0 *
S e ma gl uti de 2. 4 m g o nce wee kl y + S D Mi daz ola m ( 2 m g)
O ut -patie nt
1 5 1 -1 6 4
N o d osi n g
Peri o d 4, Da ys 1 -2
1 6 5 -1 6 6
S D Mi daz ola m ( 2 m g) o nl y
* T here is n o se ma gl uti de a d mi nistrati o n o n Da y 1 5 0 or t hereafter .
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 a p pr o priate te m perat ure c o n diti o ns ha ve 
bee n mai ntai ne d d uri n g tra nsit f or all st u d y  i nter ve nti o ns recei ve d, a n d a n y 
discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y  i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y or a d mi nister st u d y i nter ve nti o n. 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 uto 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 bl e u p o n re q uest. Data f or n o n w or ki n g da ys 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 f or 
all site st ora ge l ocati o ns u p o n ret ur n t o b usi ness.
3.
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 a ny acti o ns ta ke n. T he site s h o ul d 
acti vel y 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 st ora ge c o n diti o ns 
descri be d i n t he la beli n g, 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 ud 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 defi niti o n of a n e xc ursi o n 
a n d i nf or mati o n t he site s h o ul d re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he si te 
i n t he I P ma n ual.
4.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge 
c o n diti o ns state d o n t he la bel.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 0
5.
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.
6.
T he i n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i n stit uti o n ( w here a p plica ble) 
is res p o nsi ble f or st u dy 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 
I P 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.
7.
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 IP m a n ual. All destr ucti o n m ust be a de q uatel y  
d oc u me nte d. If destructi o n is a ut h orize d t o ta ke place at t he i n vesti gat or site, t he 
i n vesti gat or m ust e ns ure t hat t he materials are destr o ye d i n c o m plia nce wit h 
a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns 
pr o vi de d b y Pfizer.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, t he s p o ns or m ust be n otifie d w it hi n 1 b usi ness 
da y  of disc o ver y as descri be d i n t he IP m a n ual.
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a d mi nistrati o n or dis pe nsi n g t o t he partici pa nt b y q ualifie d 
staff.  Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mita nt treat me nts, 
a n d acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healthcare pr o vi der, 
partici pa nt i n acc or da nce wit h t his pr ot oc ol.  L ocal 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.
Ta blets will be dis pe ns e d at t he C R U i n t he i n di vi d ual d osi n g c o ntai ners b y  2 o perat ors, 1 of 
w h o m is a n a p pr o priatel y q ualifie d a n d e x perie nce d me m ber of t he st u d y staff (e g, p h ys icia n, 
n urse, p h ys icia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist).  
T he ta blets 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 cli nical site’s la beli n g re q uire me nts. 
T he c o m merciall y  a vaila ble pr o d ucts mi daz ola m , o me praz ole, a n d t he O C pr o vi de d b y t he 
C R U, a n d se ma gl uti de ( Oze m pic or We g o v y) pr o vi de d b y  t he Pfizer , will be pre pare d as per 
t he la bel a n d i n acc or da nce wit h t he p r ot oc ol by 2 o perat ors, 1 of w h o m is a n a p pr o priatel y 
q ualifie d a n d e x perie nce d me m ber of t he st u d y staff (e g, p h ysicia n, n urse, p h ysicia n’s 
assista nt, n urse practiti o ner, p har mac y  assista nt/tec h nicia n, or p har macist).  T he ta blets
( o me praz ole, O C a n d P F-0 7 0 8 1 5 3 2), s yr u p ( mi daz ola m) , or si n gle -d ose prefille d pe ns 
(se ma gl uti de) 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 cli nical site’s la beli n g re q uire me nts.
6. 3. Assi g n me nt t o St u d y I nter ve nti o n
T his is a n o n -ra n d o mize d, o pe n-la bel st u dy.  T he i n vesti gat or’s k n o wle d ge of t he treat me nt 
s h o ul d n ot i nfl ue nce t he decisi o n t o e nr oll a partic ular partici pa nt or affect t he or der i n w hic h 
partici pa nts are e nr olle d.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 1
T he i n vesti gat or will assi g n partici pa nt n u m bers t o t he partici pa nts as t he y  are scree ne d f or 
t he st u d y.  T he first f o ur di gits of t he S SI D will reflect t he s p o ns or-assi g ne d site n u m ber a n d 
t he re mai ni n g f o ur di gits will reflect eac h partici pa nt’s u ni q ue n u m ber assi g ne d i n 
c hr o n ol o gical or der as i nf or me d c o nse nt is o btai ne d.  I n a d diti o n, o n Da y  1 of Peri o d 1, eac h 
partici pa nt w h o is d ose d wit h t he i n vesti gati o nal pr o d uct will be assi g ne d a se parate, disti nct 
n u m ber (as pr o vi de d t o t he site b y  t he S p o ns or at t he start of t he st u d y) t o e na ble e xec uti o n of 
S p o ns ors’sta n dar d pr ocesses f or a nal y sis of all P K-relate d sa m ples. 
I n C o h ort 1 ( Peri o ds 3 t o 8) partici pa nts will recei ve t he P F - 0 7 0 8 1 5 3 2 d oses as descri be d i n
Ta ble 1 0 .  I n C o h ort 2 ( Peri o ds 2 a n d 3) partici pa nts will recei ve t he se ma gl uti de d oses as 
descri be d i n Ta ble 1 1 .  
T a ble 1 0 . P F -0 7 0 8 1 5 3 2 D osi n g Re gi me ns i n C o h ort 1
Peri o d & P F -
0 7 0 8 1 5 3 2 D ose ( d ose d 
o nce d ail y)
N u m ber of P F -0 7 0 8 1 5 3 2 T a blets
T ot al N u m ber of 
T a blets
2 0 m g
6 0 m g
1 0 0 m g
Peri o d 3: 2 0 m g
1
-
-
1
Peri o d 3: 4 0 m g
2
-
-
2
Peri o d 3: 6 0 m g
-
1
-
1
Peri o d 3: 8 0 m g
1
1
-
2
Peri o d 4 : 8 0 m g
1
1
-
2
Peri o d 5 : 8 0 m g
1
1
-
2
Peri o d 6 : 10 0 m g
-
-
1
1
Peri o d 6: 1 2 0 m g
1
-
1
2
Peri o d 6: 1 4 0 m g
2
-
1
3
Peri o d 6: 1 6 0 m g
-
1
1
2
Peri o d 6: 1 8 0 m g
1
1
1
3
Peri o d 6: 2 0 0 m g
-
-
2
2
Peri o d 6: 2 2 0 m g
1
-
2
3
Peri o d 6: 2 4 0 m g
2
-
2
4
Peri o d 6: 2 6 0 m g
-
1
2
3
Peri o d 7: 2 6 0 m g
-
1
2
3
Peri o d 8: 2 6 0 m g
-
1
2
3
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 2
T a ble 1 1 . Se m a gl uti de D osi n g Re gi me ns i n C o h ort 2
Peri o d
Wee kl y D ose
D ose per I njecti o n ( pre -fille d, 
dis p os a ble, si n gle -d ose pe ns)
T ot al Stre n gt h per T ot al 
V ol u me
Peri o d 2 : Wee ks 1 - 4
0. 2 5 m g
0. 2 5 m g
0. 2 5 m g / 0. 5 m L
Peri o d 2 : Wee ks 5 - 8
0. 5 m g
0. 5 m g
0. 5 m g / 0. 5 m L
Peri o d 2 : Wee ks 9 -1 2
1. 0 m g
1. 0 m g
1. 0 m g / 0. 5 m L
Peri o d 2 : Wee ks 1 3 -1 6
1. 7 m g
1. 7 m g
1. 7 m g / 0. 7 5 m L
Peri o d 2 : Wee ks 1 7 -2 1
2. 4 m g
2. 4 m g
2 . 4 m g / 0. 7 5 m L
Peri o d 3 : Da y 1
2. 4 m g
2. 4 m g
2 . 4 m g / 0. 7 5 m L
St u d y  i nter ve nti o n will be dis pe nse d at t he st u d y visits as s u m marize d i n t he S o A . Ret ur ne d 
st u d y i nter ve nti o n m ust n ot be re dis pe nse d t o t he partici pa nts.
6. 4. Bli n di n g
N ot a p plica ble as t his is a n o n -ra n d o mize d, o pe n-la bel st u d y. 
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n 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 an 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 sta ff 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 dy site pers o n nel will e x a mi ne e ac h p artici p a nt’s m o ut h t o e ns ure t h at t he st u dy 
i nterve nti o n (e xce pt se m a gl uti de) w as i n geste d ; t his is vit ally i m p ort a nt t o e ns ure d osi n g 
c o m pli a nce i n lig ht of t he p ote nti al g astr oi ntesti n al A Es .
A d diti o n ally, if v o miti n g occ urs 
f oll o wi n g or al d osi n g a n d u p t o 4 h o urs p ost -d ose (t wice t he me di a n Tm a x of P F - 0 7 0 8 1 5 3 2), 
site pers o n nel will e x a mi ne t he e mesis f or evi de nce of dr u g pr o d uct. A d diti o nall y , f or 
C o h ort 2, eac h wee kl y i njecti o n of se ma gl uti de will be d oc u me nte d b y st u d y site staff .
6. 6. D ose M o dific ati o n
If partici pa nts are n ot a ble t o t olerate titrati o n t o hi g her d oses of P F -0 7 0 8 1 5 3 2
(e g, ≥22 0 m g Q D ) or se ma gl uti de t he d ose ma y be te m p orarily d o w n -titrate d, titrati o n t o t he 
ne xt d ose le vel ma y  be dela ye d te m p oraril y, or titrati o n t o a ma xi m u m t olerate d d ose ma y  be 
per mitte d, wit h S p o ns or a p pr o val o nl y.
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 i nter ve nti o n will be pr o vi de d t o st u d y  partici pa nts at t he e n d of t heir st u d y partici pati o n .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 3
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 0 8 1 5 3 2 greater t ha n 1. 6 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. A si n gle d ose of 1. 6 g is pr ojecte d t o res ult i n e x p os ure t hat will 
e xcee d t hat o bser ve d at t he N O A E L i n t he pi v otal 9 -m o nt h t o xic ol o g y  st u d y i n m o n ke ys, 
after acc o u nti n g f or s pecies differe nces i n plas ma pr otei n bi n di n g. 
F or t his st u d y , o ver d ose f or mi daz ola m ,1 3 o me praz ole, 1 4 t he O C1 5 or se ma gl uti de 1 6 ,1 7 will be 
as per t he U S PI la bel.
T here is n o s pecific treat me nt f or a n o ver d ose f or P F - 0 7 0 8 1 5 3 2.  Treat me nt of o ver d ose 
s h o ul d c o nsist of ge neral s u p p orti ve meas ures.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d:
1.
C o ntact t he 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 Es/ S A Es a n d la b orat or y  a b n or malities f or at 
least 5 half-li ves (a p pr o xi matel y 5 da ys) after t he o ver d ose of st u d y i nter ve nti o n, a n d 
as me dicall y a p pr o priate u ntil t he ne xt sc he d ule d f oll o w - u p.
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 ve r d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E .
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 1 da y fr o m t he date of t he last d ose of 
st u d y i nter ve nti o n if re q ueste d b y t he me dical m o nit or ( deter mi ne d o n a case-b y -case
basis).  
Decis i 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 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. C o nc o mit a nt T her a p y
St u d y  partici pa nts will a bstai n fr o m all c o nc o mita nt treat me nts, e xce pt f or t he treat me nt of 
A Es , as descri be d i n t he E xcl usi o n Criteria secti o ns of t his pr ot oc ol.
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
(e g, St. J o h n’s w ort) 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 dy i nter ve nti o n.  S yste mic t hera p y wit h a n y me dicati o ns t hat are m o derate 
or str o n g C Y P 3 A 4/ 5 a n d/ or C Y P 2 C 1 9 i n hi bit ors or m o derate or str o n g C Y P 3 A 4/ 5 a n d/ or 
C Y P 2 C 1 9 i n d ucers wit hi n 1 4 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 mi daz ola m a n d o me praz ole are pr o hi bite d .
Use of a G LP- 1 R a g o nist is pr o hi bite d wit hi n 9 0 da ys pri or t o t he first d ose of st u d y 
i nter ve nti o n.  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 4
H or m o nal c o ntrace pti ves (i ncl u di n g oral a n d n o n-oral) are n ot all o we d t o be use d i n 
partici pa nts w h o are W O C B P (see A p pe n di x 4 ).
Fe males usi n g h or m o nal c o ntrace pti ves or ta ki n g h or m o ne re place me nt t hera p y ma y be 
eli gi ble t o partici pate i n t his st u d y if t he y are willi n g t o disc o nti n ue t hera p y at least 2 8 d a y s 
pri or t o t he fir st 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.  De p o-Pr o vera ® m ust be disc o nti n ue d at least 6 m o nt hs pri or t o t he first d ose of 
st u d y treat me nt.
S y ste mic t hera p y wit h i n hi bit ors of O A T P tra ns p orters wit hi n 1 4 d a 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 are pr o hi bite d .
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 .
A nti- e metics (e g, pr oc hl or perazi ne, pr o met hazi ne, o n da nsetr o n) ma y  be a d mi nistere d at t he 
i n vesti gat or’s discreti o n wit h n otificati o n t o t he s p o ns or a n d e ntr y i n t he C R F ( See 
Secti o n 6. 9. 1. 1 ).
Sites are e nc o ura ge d t o c o ntact t he s p o ns or s h o ul d t here be q uesti o ns as t o w het her a 
me dicati o n is per mitte d or pr o hi bite d.
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 as liste d i n t he S o A .
Treat me nts ta ke n wit hi n 2 8 da y s bef ore t he first d ose of st u d y i nter ve nti o n will be 
d oc u me nte d as a pri or treat me nt.  Treat me nts ta ke n after t he first d ose of st u d y  i nter ve nti o n 
will be d oc u me nte d as c o nc o mita nt treat me nts.
6. 9. 1. Resc ue Me dici ne
T here is n o resc ue t hera p y t o re verse t he A Es o bser ve d wit h P F - 0 7 0 8 1 5 3 2; sta n dar d me dic al 
s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es, i ncl u di n g a d mi nistrati o n of 
car b o h y drates t o treat H A E s (see Secti o n 8. 3. 6 ).
6. 9. 1. 1.
M a n a ge me nt of N a use a a n d V o miti n g
Na usea a n d v o miti n g ha ve bee n re p orte d wit h a d mi nistrati o n of G L P- 1 R a g o nists a n d als o 
wit h a d mi nistrati o n of P F - 0 7 0 8 1 5 3 2 (see Secti o n 2. 2. 4 ).  St u d y partici pa nts c o m plai ni n g of 
na usea ma y  be ma na ge d c o nser vativel y wit h be d rest a n d/ or fl ui d ma na ge me nt at t he 
discreti o n of t he i n vesti gat or.  If na usea a n d v o miti n g are n ot a me na ble t o c o nser vati ve 
ma na ge me nt, a nti -e metics (e g, pr oc hl or perazi ne, pr o met hazi ne, o n da nsetr o n) ma y  be 
a d mi nistere d at t he in vesti gat or’s discreti o n wit h n otificati o n t o t he s p o ns or a n d e ntr y  i n t he 
C R F .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 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
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 
( defi niti ve disc o nti n uati 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:

Criteria f or a p ote ntial H y ’s la w case are met (see A p pe n di x 6 ).

I nte nt t o bec o me pre g na nt or pre g na nc y c o nfir me d b y ser u m -h C G testi n g.  

Safet y  or t olera bility c o ncer n arises, i n partic ular if n ot res p o nsi ve t o s y m pt o matic 
ma na ge me nt, d osi n g wit h st u d y  i nter ve nti o n ma y be st o p pe d i n a n i n di vi d ual 
partici pa nt at i n vesti gat or discreti o n.  

Base d o n me ntal healt h assess me nt as o utli ne d i n Secti o n 8. 3. 8 , s h o ul d be 
disc o nti n ue d fr o m d osi n g at i n vesti gat or discreti o n.

If t he criteria f or per ma ne nt disc o nti n uati o n are met, t he site s h o ul d n otif y t he s p o ns or 
Me dical M o nit or or s p o ns or Cli nicia n.

P ositi ve S A R S -C o V - 2 Test .
N ote t hat disc 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 nt l y disc o nti n ue d, t he partici pa nt will re mai n i n t he st u d y t o 
be e val uate d f or a n E T visit.   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, p osttreat me nt 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.
A d diti o nall y , 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 or a ny p orti o n of t he st u d y (e g, C o h ort 2) at a n y ti me f or a n y reas o n (e g, i na bilit y t o 
sec ure i n vesti gati o nal pr o d uct s u p plies) at t he s ole discreti o n of t he s po ns or. ( A p pe n di x 1 , 
Secti o n 1 0. 1. 9 ).
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al
fr 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 his/ her o w n re q uest.  Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ures.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 6

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.

Safet y  or be ha vi oral reas o ns at t he discreti o n of t he i n vesti gat or, i ncl u di n g reas o ns 
relate d t o me ntal healt h assess me nts.
At t he ti me of disc o nti n uati o n fr o m t he st u d y, if p ossi ble, a n early 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 wn 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.  
If a partici pa nt wit h dra ws fr o m t he st u d y, he/s he ma y re q uest destr ucti o n of a n y re mai ni n g 
sa m ples ta ke n a n d n ot teste d, a n d t he 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 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 s h o ul d be perf or me d, a n d n o
a d diti o nal data s h o ul d 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 be f ore s uc h wit h dra wal of c o nse nt.
Lac k of c o m pleti o n of all or a n y of t he wit h dra wal/ E T pr oce d ures will n ot be vie we d as 
pr ot oc ol de viati o ns s o l o n g as t he partici pa nt’s safet y  was preserve d.
7. 2. 1. Wit h dr a w al of C o nse nt
Partici pa nt s w h o re q uest t o disc o nti n ue recei pt of st u d y i nter ve nti o n will re mai n i n t he st u d y  
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol -s pecifie d f oll o w-u p pr oce d ures. T he o nl y 
e xce pti o n t o t his is w he n a partici pa nt s pecifically wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h hi m or her or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his 
i nf or mati o n. Partici pa nt s s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o 
wit h dra w c o nse nt fr o m f ut ure f oll o w-u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt 
s h o ul d be e x plai ne d i n detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he 
wit h dra wal is o nl y  fr o m f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures 
a n d/ or p osttreat me nt st u d y f oll o w-u p, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt 
t hat vital stat us ( w het her t he partici pa nt is ali ve or dea d) is bei n g meas ure d, p u blicl y 
a vaila ble i nf or mati o n s h o ul d be use d t o deter mi ne vital stat us o nl y  as a p pr o priatel y directe d 
i n acc or da nce wit h l ocal la w.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 7
7. 3. L ost t o F ol l o w- up 
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if he or s he 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 by 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 atte n d a re q uire d st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble.
Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w - u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d;

S h o ul d t he partici pa nt c o nti n ue t o be u nre ac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y. 
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
8. 1. A d mi nistr ati ve Pr oce d ures
T he i n 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.
Safet y  iss ues s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n occ urre nce or 
a ware ness t o deter mi ne w het her t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y  
i nter ve nti o n.
A d here nce t o t he st u d y desi g n re q uire 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 u ati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria.  T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Partici pa nts will be scree ne d wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he st u d y i nter ve nti o n 
t o c o nfir m t hat t he y meet t he st u d y p o p ulati o n criteria f or t he st u d y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 8
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 y  ma ke it u nfeasi ble t o perf or m 
t he test.  In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y t o e ns ure t he safety a n d 
well bei n g of t he partici pa nt.  W he n a pr ot oc ol re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat he or s he has ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble.  T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
If a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g n assess me nts 
( p ulse rate a n d B P) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter. 
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nts i n t his st u d y  is a p pr o xi matel y
8 8 0 m L  i n C o h ort 1 a n d 4 0 0 m L  i n C o h ort 2 .  The t otal bl o o d v ol u me ta ke n d oe s n ot e xcee d 
5 5 0 m L  i n a ny gi ve n 5 6- da y c o nsec uti ve peri o d of ti me f or eit her C o h ort 1 or 2.  T he act ual 
c ollecti o n ti mes of bl o o d sa m pli n g ma y  c ha n ge.  A d diti o nal bl o o d sa m ples ma y be ta ke n f or 
safety assess me nts at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal v ol u me ta ke n d uri n g t he
st u d y d oes n ot e xcee d 5 5 0 m L  d uri n g a n y peri o d of 5 6 c o nsec uti ve da ys.
T o pre pare f or st u dy 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
N ot a p plica ble.
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 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 dy t o assess a n y 
percei ve d safet y  iss ues.
8. 3. 1. P h ysic al E x a mi n ati o ns
A c o m plete p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, hea d, ears, e ye s, n ose, m o ut h, 
s ki n, heart a n d l u n g e xa mi nati o ns, l ym p h n o des, a n d gastr oi ntesti nal, m usc ul os keletal, a n d 
ne ur ol o gical s ys te ms. 
A brief p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of ge neral a p peara nce, 
t he res pirat or y a n d car di o vasc ular sys te ms, a n d partici pa nt -re p orte d sy m pt o ms.
C o m plete p h y sical e xa m will be d o ne at ti me p oi nts s pecifie d i n t he S o A ot her wise, brief 
e xa m if fi n di n gs d uri n g pre vi o us e xa m or ne w/ o pe n A Es, if a p pr o priate, at i n vesti gat or 
discreti o n.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 9
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 .  Hei g ht will be 
meas ure d at scree ni n g o nl y .  Wei g ht will be rec or de d usi n g a cali brate d scale ( wit h t he sa me 
scale use d if p ossi ble, f or t he d urati o n of t he st u d y) re p orti n g wei g ht i n eit her p o u n ds (l b) or 
k il o gra ms ( k g), a n d acc urac y t o t he nearest 0. 2 l b ( or 0. 1 k g); ie, t he de vice m ust be a ble t o 
disti n g uis h a differe nce bet wee n 1 5 0. 4 l b ( 6 8. 4 k g) vers us 1 5 0. 2 l b ( 6 8. 3 k g).  T he scale m ust 
be place d o n a sta ble, flat s urface.  
Wei g ht meas ure me nt s h o ul d be ta ke n u n der t he f oll o wi n g c o n diti o ns:

I n t he m or ni n g i n a fasti n g state.

After v oi d of uri ne.

After re m o val of 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.

After r e m o val of p oc ket c o nte nts. 

W hile re mai ni n g still d uri n g t he meas ure me nt.
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 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 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 ( 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 n 8. 4. 1 t o 8. 4. 3 .
8. 3. 2. Vit al Si g ns
Vital si g ns (s ys t olic B P, diast olic B P a n d P R ) will occ ur as s pecifie d i n t he S o A .  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 s u pi ne rest.  T he sa me ar m ( prefera bly 
t he d o mi na nt ar m) will be use d t hr o u g h o ut t he st u d y.  Partici pa nts s h o ul d be i nstr ucte d n ot t o 
s pea k d uri n g meas ure me nts.  W he n tri plicate meas ure me nts are o btai ne d, t he y s h o ul d be 
c ollecte d a p pr o xi matel y 2 mi n utes a part. 
At S cree ni n g, t he partici pa nt’s ar m circ u mfere nce s h o ul d be meas ure d (e g, usi n g a fle xi ble 
a nt hr o p o metric ta pe) at t he mi d p oi nt of t he le n gt h of t he u p per ar m a n d t he a p pr o priate c uff 
selecte d a n d use d t hr o u g h o ut t he st u d y.  T he sa me pr o perl y size d a n d cali brate d B P c uff will 
be use d t o meas ure B P eac h ti me.  
T he use of a n a ut o mate d de vice f or meas uri n g B P a n d P R is acce pta ble; b ut 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 R s h o ul d 
be o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n. 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 0
A d diti o nal c ollecti o n ti mes, or c ha n ges t o c ollecti o n ti mes, of B P a n d P R will be per mitte d, 
as necessar y, t o e ns ure a p pr o priate c ollecti o n of safety data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o n 8. 4. 1 t o 8. 4. 3 .
8. 3. 2. 1. Te m per at ure
B o d y te m perat ure will be meas ure d at t he ti me p oi nts liste d i n t he S o A .  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. 3. Electr oc ar di o gr a ms
Sta n dar d 1 2 -lea d EC Gs utilizi n g li m b lea ds ( wit h a 1 0 sec o n d r hyt h m stri p) s h o ul d 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 mac hi ne t hat 
aut o maticall y  calc ulates t he H R a n d meas ures P R, Q T, a n d Q Tc F i nter vals a n d Q R S 
c o m ple x .  Alter nati ve lea d place me nt met h o d ol o g y usi n g t ors o lea ds ( e g, Mas o n L i kar) is n ot 
rec o m me n de d gi ve n t he p ote ntial ris k of discre pa ncies wit h E C Gs ac q uire d usi n g sta n dar d 
li m b lea d place me nt. All sc he d ule d E C Gs s h o ul d be perf or me d after t he partici pa nt has 
reste d q uietl y f or at least 1 0 mi n utes i n a s u pi ne p ositi o n. 
T o e ns ure safety of t he partici pa nts, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o scree ni n g meas ure me nts.  A d diti o nal E C G m o nit ori n g will occ ur if 
a) a p ost d ose Q Tc F i nter val is i ncrease d b y ≥6 0 msec fr o m t he scree ni n g a n d is > 4 5 0 msec ; 
or b) a n a bs ol ute Q Tc F val ue is ≥5 0 0 msec f or a n y sc he d ule d E C G.  If eit her of t hese 
c o n diti o ns occ urs, t he n 2 a d diti o nal E C Gs will be c ollecte d a p pr o xi matel y  2 t o 4 mi n utes 
a part t o c o nfir m t he ori gi nal meas ure me nt.   If t he Q TcF val ues fr o m t hese re peate d E C Gs 
re mai n a b o ve t he t hres h ol d val ue, t he n a si n gle E C G m ust be re peate d at least h o urly u ntil 
Q Tc F val ues fr o m 2 s uccessi ve E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat 
meas ure me nt.
If a) a p ost d ose Q Tc F i nter val re mai ns ≥3 0 msec fr o m the scree ni n g a n d is > 4 5 0 msec; or 
b) a n a bs ol ute Q Tc F val ue is ≥5 0 0 msec f or a n y s c he d ule d E C G f or greater t ha n 4 h o urs ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or); or c) Q Tc F i nter vals get pr o gressi vel y l o n ger, 
t he partici pa nt s h o ul d u n der g o c o nti n u 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 Tc i nter vals d o n ot ret ur n t o less t ha n t he criteri o n liste d a b o ve after 8 h o urs of 
m o nit ori n g ( or s o o ner , at t he discreti o n of t he i n vesti gat or). 
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y.  It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs.  If a mac hi ne rea d
Q Tc F 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 val ues are i n t he 
acce pta ble ra n ge.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 1
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 8 .
8. 3. 4. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A . 
U nsc he d ule d cli nical la b orat or y  meas ureme nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.  
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y 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.
Cli nicall y  si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h 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 ntly 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 -3 5 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 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. 4. 1. Alter n ati ve F acilities f or Cli nic al S afet y L a b or a t or y Assess me nt
If a l ocal la b orat or y is use d, q ualifie d st u d y site pers o n nel m ust or der, recei ve, a n d re vie w 
res ults. Site staff m ust c ollect t he l ocal la b orat or y refere nce ra n ges a n d certificati o ns/
accre ditati o ns f or fili n g at t he site.   La b orat or y test res ults are t o be pr o vi de d t o t he site staff 
as s o o n as p ossi ble.   T he l ocal la b orat or y  re p orts s h o ul d be file d i n t he partici pa nt’s s o urce
d oc u me nts/ me dical rec or ds. Rele va nt data fr o m t he l ocal la b orat or y  re p ort s h o ul d 
be  rec or de d o n t he C R F.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 2
8. 3. 5. C O VI D - 1 9 Specific A ssess me nts
C o h ort 1: Partici pa nts will be teste d f or S A R S -C o V - 2 i nfecti o n by P C R pri or t o bei n g 
a d mitte d t o t he cli nic f or c o nfi ne me nt i n Peri o ds 1 a n d 9.  A s u bse q ue nt test will als o be d o ne
acc or di n g t o l ocal pr oce d ure, if partici pa nts de v el o p s ym pt o ms s u g gesti ve of C O VI D - 1 9. If 
partic i pa nts test p ositi ve f or S A R S -C o V -2 i nfecti o n, t he y  will be disc har ge d fr o m t he st u d y. 
C o h ort 2: Partici pa nts will be teste d f or S A R S -C o V - 2 i nfecti o n by P C R pri or t o bei n g 
a d mitte d t o t he cli nic f or c o nfi ne m e nt i n Peri o ds 1, 3 a n d 4.  A s u bse q ue nt test will als o be 
d o ne acc or di n g t o l ocal pr oce d ure, if partici pa nts de vel o p s ym pt o ms s u g gesti ve of 
C O VI D - 1 9.  If partici pa nts test p ositi ve f or S A R S-C o V -2 i nfecti o n, t he y  will be disc har ge d 
fr o m t he st u d y.
A d diti o nal testi n g ma y  be re q uire d b y l ocal re g ulati o ns or b y t he Pri nci pal I n vesti gat or.
Res ults m ust be ne gati ve f or a d missi o n t o t he C R U . 
8. 3. 6. M a n a ge me nt of H y p o gl yce mi a
W hile h y p o gl yc e mia is n ot e x pecte d i n t he st u d y partici pa nts, fasti n g bl o o d gl uc ose will be 
meas ure d as part of la b orat or y  assess me nt per t he S o A .  In a d diti o n, as a preca uti o n, 
partici pa nts will be m o nit ore d f or t he si g ns a n d s y m pt o ms ass ociate d wit h h y p o gl yc e mia. 
A n y  e pis o de of h yp o gl yc e mia m ust be ca pt ure d o n t he H A E C R F wit h s pecific details 
ca pt ure d o n t he H A E F or m C R F.  F or t he defi niti o n of a h y p o gl yce mic e pis o de a n d se verit y 
cate g orizati o n see Secti o n 8. 3. 6. 1 bel o w.
F or me dical ma na ge me nt of h y p o gl yc e mia, t he i n vesti gat or ma y a d mi nister oral 
car b o h y drate, gl uca g o n, or I V gl uc ose acc or di n g t o his or her me dical j u d g me nt.  
8. 3. 6. 1. Defi niti o n a n d Se verit y of C ate g oriz ati o n of H y p o gl yce mic A d verse E ve n t 
( H A E)
T he i n vesti gat or m ust assess t he gl uc ose val ues re p orte d b y t he ce ntral/l ocal la b orat or y, as 
well as a n y si g ns or s ym pt o ms re p orte d by t he st u d y  partici pa nt.
H A E is defi ne d as o ne of t he f oll o wi n g: 5 1
a.
As y m pt o matic h y p o gl yc e mia: A n e ve nt n ot acc o m pa nie d b y  ty pical s y m pt o ms of 
H A E b ut a gl uc ose val ue of < 7 0 m g/ d L  ( 3. 9 m m ol/ L) usi n g eit her gl uc o meter 
(fi n gerstic k bl o o d gl uc ose) at t he st u dy s ite or s p o ns or-i de ntifie d ce ntral/l ocal 
la b orat or y ( bl o o d gl uc ose).
b.
D oc u me nte d s y m pt o matic h y p o gl yc e mia: A n e ve nt d uri n g w hic h t y pical s y m pt o ms 
of H A E are acc o m pa nie d wit h a gl uc ose val ue of < 7 0 m g/ d L ( 3. 9 m m ol/ L), usi n g 
gl uc o meter at t he st u d y s ite or s p ons or i de ntifie d ce ntral/l ocal la b orat or y , a n d t he 
cli nical pict ure i ncl u des pr o m pt res ol uti o n wit h f o o d i nta ke, s u bc uta ne o us gl uca g o n, 
or I V gl uc ose.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 3
c.
Pr o ba ble s y m pt o matic h y p o gl yc e mia: A n e ve nt d uri n g w hic h s ym pt o ms of H A E are 
n ot acc o m pa nie d b y a gl uc ose deter mi nati o n b ut was pres u ma bl y ca use d b y a gl uc ose 
c o nce ntrati o n of < 7 0 m g/ d L ( 3. 9 m m ol/ L), a n d t he cli nical pict ure i ncl u des pr o m pt 
res ol uti o n wit h f o o d i nta ke, s u bc uta ne o us gl uca g o n, or I V gl uc ose.
Eac h e pis o de of H A E m ust be cate g orize d wit h res pect t o se verit y.  I n or der t o c haracterize 
t he e ve nt as se vere, all 3 criteria bel o w m ust be met:
1.
T he partici pa nt was u na ble t o treat hi m/ herself.  Ne ur ol o gic i m pair me nt, a n d n ot t he 
a ge of t he partici pa nt, is t he e x pla nati o n f or w h y t he partici pa nt c o ul d n ot t reat 
hi m/ herself a n d re q uire d t he assista nce of a n ot her pers o n.
2.
T he partici pa nt e x hi bite d at least 1 of t he f oll o wi n g ne ur ol o gical s y m pt o ms:

Me m or y  l oss.

C o nf usi o n.

U nc o ntr olle d be ha vi or.

Irrati o nal be ha vi or.

U n us ual diffic ult y  i n a wa ke ni n g.

S us pecte d seiz ure.

Seiz ure.

L oss of c o nsci o us ness.
3.
Eit her :

If bl o o d gl uc ose was meas ure d a n d was ≤5 4 m g/ d L ( 2. 7 m m ol/ L) usi n g 
gl uc o meter ( or ce ntral /l ocal la b orat or y); or

If bl o o d gl uc ose was n ot meas ure d, t he cli nical ma nifestati o ns were re verse d b y 
oral car b o h y drates, s u bc uta ne o us gl uca g o n, or I V gl uc ose.
E ve nts t hat d o n ot meet all t he criteria a b o ve f or se vere H A E are c haracterize d as mil d or 
m o derate i n se verit y .
8. 3. 6. 2. Gl uc o meter M o nit ori n g of Gl uc ose
M o nit ori n g of F S B G usi n g gl uc o meter meas ure me nts is n ot re q uire d per pr ot oc ol b ut ma y  be 
o btai ne d if t he i n vesti gat or or partici pa nt n otes s y m pt o ms of h y p o gl y ce mia.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 4
If o btai ne d, F S B G rea di n gs will be mai ntai ne d at t he C R U i n s o urce d oc u me nts, a n d o nl y t he 
gl uc ose res ults fr o m t he la b orat or y  will be re p orte d i n t he st u d y data base.
If a n F S B G res ult is ≤7 0 m g/ d L, a sec o n d F S B G s h o ul d be o btai ne d t o c o nfir m t he gl uc ose 
val ue, i n a d diti o n t o a ve n o us sa m ple t hat will be se nt t o t he cli nical la b orat or y  f or 
c o nfir mati o n.  If t he val ue fr o m t his sec o n d F S B G is als o ≤7 0 m g/ d L , t he sec o n d val ue will 
be rec or de d as a h y p o gl yce mic A E.  F S B G will c o nti n ue t o be m o nit ore d u ntil t he gl uc ose 
val ue ret ur ns t o > 7 0 m g/ d L .  Sa m ples ma y be ta ke n m ore fre q ue ntly if dee me d necessar y  b y 
t he i n vesti gat or.  
8. 3. 7. Pre g n a nc y Testi n g 
A ser u m pre g na nc y  test is re q uire d at scree ni n g. Pre g na nc y  tests ma y be uri ne or ser u m tests 
b ut m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L.
Pre g na nc y  tests will be perf or me d i n 
W O C B P at t he ti mes liste d i n t he S o A .  F oll o wi n g a ne gati ve pre g na nc y  test res ult at 
scree ni n g, a p pr o priate n o n h or m o nal c o ntrace pti o n m ust be c o m me nce d, a n d a sec o n d 
ne gati ve pre g na nc y  test res ult will be re q uire d at t he baseli ne visit pri or t he partici pa nt’s 
recei vi n g t he st u dy i nter ve nti o n/st u d y  treat me nt. Pre g na nc y  tests will als o be d o ne w he ne ver 
1 me nstr ual c y cle is misse d d uri n g t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y  
is ot her wise s us pecte d) a n d at t he e n d of t he st u dy. Pre g na nc y  tests ma y als o be re peate d if 
re q ueste d by I RBs/ E Cs or if re q uire d b y  l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d 
as ne gati ve (e g, a n a m bi g u o us res ult), a ser u m pre g na nc y  test is re q uire d. I n s uc h cases, t he 
partici pa nt m ust be e xcl u de d if t he ser u m pre g na nc y  res ult is p ositi ve.
8. 3. 8. S uici d al I de ati o n a n d Be h a vi or Ris k M o nit ori n g 
8. 3. 8. 1. C ol u m bi a S uici de Se verit y R ati n g Sc ale ( C -S S R S)
T he C -S S R S is a n i nter vie w-base d rati n g scale t o s yste maticall y assess s uici dal i deati o n a n d 
s uici dal be ha vi or. 4 3  T he “ baseli ne/ scree ni n g” versi o n of t he C -S S R S will be a d mi nistere d at 
Scree ni n g a n d Da y  -1 i n st u d y .  Partici pa nts w h o res p o n d “ y es” t o Q uesti o n 4 or 
5 (i n dicati n g s uici dal i deati o n), or t o a n y s uici dal be ha vi oral q uesti o n o n t he C -S S R S at 
scree ni n g or Da y- 1 will n ot be per mitte d i n t he st u d y (see Secti o n 5. 2 ).  T he “si nc e last visit ” 
versi o n of t he C -S S R S will be a d mi nistere d a t t he ti me p oi nts s pecifie d i n t he S o A .  T he 
C- S S R S will be a d mi nistere d b y st u d y site staff w h o ha ve c o m plete d trai ni n g i n its 
a d mi nistrati o n .
8. 3. 8. 1. 1. R ater Q u alific ati o ns
F or s pecific rati n g assess me nts, o nl y  q ualifie d raters will be all o we d t o e val uate a n d/ or rate 
partici pa nts i n t his st u d y .  T he mi ni m u m q ualificati o ns a rater m ust meet f or eac h st u dy 
rati n g assess me nt will be o utli ne d i n t he g ui da nce d oc u me nt pr o vi de d t o eac h partici pati n g 
site.  T he le vel of e x perie nce wit h t he tar get p o p ulati o n ( or e q ui vale nt), s pecific scale 
e x perie nce ( or e q ui vale nt), a n d certificati o n re q uire d (if a p plica ble) will be liste d a n d use d t o 
deter mi ne w het her a rater is a p pr o ve d f or a gi ve n assess me nt.  T he rater m ust bec o me 
certifie d t o perf or m selecte d st u d y  assess me nts bef ore he or s he ca n partici pate i n t he c o n d uct 
of t he st u d y .  F or s pecificall y defi ne d assess me nts, rater trai ni n g a n d sta n dar dizati o n 
e xercises ma y be c o n d ucte d, a n d writte n a n d si g ne d d oc u me ntati o n will be pr o vi de d b y t he 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 5
site f or eac h rater’s certificati o n.  In ret ur n, eac h site will be pr o vi de d wit h writte n a n d si g ne d 
d oc u me ntati o n o utli ni n g eac h rater’s certificati o n f or s pecific st u d y  assess me nts.  
Recertificati o n ma y be re q uire d at peri o dic i nter vals d uri n g t he st u d y .  T he raters w h o 
a d mi nister s pecific st u d y assess me nts will be d oc u me nte d i n a ce ntralize d l ocati o n a n d all 
site staff w h o a d mi nister rati n gs will be verifie d i n t he site st u d y d oc u me ntati o n d uri n g t he 
c on d uct of t he st u d y.
8. 3. 8. 2. P atie nt He alt h Q uesti o n n aire -9 ( P H Q - 9)
T he P H Q -9 is a 9 ite m self -re p ort scale f or t he assess me nt of de pressi ve sy m pt o ms. 4 8 T he 
P H Q -9 will be c o m plete d b y  partici pa nts a n d re vie we d by site staff at t he pre -defi ne d ti me 
p oi nts o utli ne d i n t he S o A .  A P H Q-9 sc ore of ≥1 5 at Scree ni n g or Da y  -1 i n dicates cli nicall y 
si g nifica nt de pressi o n a n d ser ves as a n e xcl usi o n criteri o n f or t his st u d y (see Secti o n 5. 2 ).
8. 3. 8. 3. Referr al t o a Me nt al H e alt h P r ofessi o n al
A partici pa nt s h o ul d be referre d t o a M H P f or t he f oll o wi n g reas o ns:

Res p o nse of “ y es” t o q uesti o n 4 or 5 , or o n a n y s uici dal be ha vi oral q uesti o n o n t he 
C- S S R S .

A sc ore of ≥1 5 o n t he P H Q - 9.

I n t he i n vesti gat or’s j u d g me nt a ris k assess me nt or e xcl usi o n is re q uire d.
A cli nicall y q ualifie d M H P is a n M H P wit h a p pr o priate trai ni n g i n t he assess me nt of s uici de 
ris k, acc or di n g t o l ocal cli nical practice sta n dar ds a n d re g ulati o ns, w h o w o ul d n or mall y  
e val uate t he ris k f or s uici dal i deati o n a n d be ha vi or i n a patie nt.
Partici pa nts w h o ha ve rec urre nt s uici dal i deati o n or be ha vi or d uri n g t he st u d y  s h o ul d be 
disc o nti n ue d fr o m t he st u d y  a n d treate d a p pr o priatel y. If a st u d y partici pa nt e n d orses a 4 or 
5 o n t he i deati o n s u bscale or a n y be ha vi oral ite m of t he C -S S R S o n 2 or m ore occasi o ns a n d 
is c o nfir me d t o ha ve acti ve s uici dal i deati o n or be ha vi or o n b ot h occasi o ns b y a ris k
assess me nt c o n d ucte d b y a q ualifie d M H P, t h e n t he partici pa nt s h o ul d be disc o nti n ue d fr o m 
t he st u d y a n d treate d a p pr o priately.
Partici pa nts w h o meet criteria f or referral t o a M H P b ut
ref use e val uati o n a n d/ or treat me nt by 
a M H P, m ust be assesse d b y  t he i n vesti gat or t o deter mi ne if t he partici pa nt s h o ul d be 
disc o nti n ue d fr o m d osi n g or fr o m t he st u d y. 
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 Es 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 I n vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc.).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 6
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o assess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 4. 1 , eac h partici pa nt will be 
q uesti o ne d a b o ut t he occ urre nce of A Es i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y  be re q ueste d b y Pfizer Safety t o o btai n s pecific f oll o w - u p 
i nf ormati o n i n a n e x pe dite d fas hi o n.
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g A Es 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 d es i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore t he partici pa nt ’s partici pati o n i n t he st u d y (ie, 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 a n d after 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 t o a le vel acce pta bl e t o t he 
i n vesti gat or.
W he n a cli nicall y  i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
F or partici pa nts w h o are scree n fail ures, t he acti ve c 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 b e rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A E s or S A 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 n y 
S A E, i ncl u di n g a deat h, at a n y  ti me after a partici pa nt has c o m plete d t he st u d y, a n d he/s he 
c o nsi ders 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 7
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n 
Secti o n 8. 4. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m i m me diatel y u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it bei n g a vaila ble.
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 4. 1 , will be rec or de d 
o n t he A E secti o n of t he C R F.
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d, a n d all s p o nta ne o usl y re p orte d 
A Es a n d S A Es re p orte d b y  t he partici pa nt.
As par t of o n g oi n g safety re vie ws c o n d ucte d b y t he s p o ns or, a n y n o nseri o us A E t hat is 
deter mi ne d b y t he s p o ns or t o be seri o us will be re p orte d b y t he s p o ns or as a n S A E. T o assist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
Re p orti n g of A Es a n d S A Es f or partici pa nts w h o fail scree ni n g are s u bject t o t he C R F 
re q uire me nts as descri be d i n Sect i o n 5. 4 .
8. 4. 2. Met h o d of Detecti n g A Es 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 A Es 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 mitt i n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A Es 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 Es 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 m ati 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 n y i nf or mati o n rele va nt t o t he e ve nt, s uc h as c o nc o mita nt me dicati o ns 
a n d ill nesses, m ust be pr o vi de d.  I n t he case of a partici pa nt deat h, a s u m mar y of a vaila ble 
a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble t o Pfizer Safet y. 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 8
F urt her i nf or mati o n o n f oll o w- u p- pr oce d ures is gi ve n 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 n si bilities t o war d t he safety of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y s pecific- re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I R B s/ E Cs, a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n ( e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 4. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o vi ders, fa mily me m bers, a n d ot hers w h o ma y be e x p ose d. 
E n vir o n me ntal e x p os ure ma y i ncl u de e x p os ure d uri n g pre g na nc y, e x p os ure d uri n g 
breastfee di n g, a n d occ u pati o nal e x p os ure.
A n y  s uc h ex p os ure 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 Safety 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
8. 4. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if: 

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A fe male 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 d ue t o e n vir o n me ntal e x p os ure. Bel o w are e xa m ples of 
e n vir o n me ntal E D P : 

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha v i n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y i n gesti o n.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 9
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 antici 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 a partici pa nt’s part ner, t he i n vesti gat or m ust re p ort 
t his i nf or mati o n t o Pfizer Safet y o n t he C T S A E Re p ort F or m a n d a n E D P 
S u p ple me ntal F or m, re gar dless of w het her a n S A E has occ urre d. Details of t he 
pre g na nc y  will be c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil 2 8 da y s after 
t he last d ose.

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. 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 stu 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 C T S A E Re p ort F or m 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 an 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 E D P Su p ple me ntal F or m. I n t he case of a li ve birt h, t he str uct ural 
i nte grity 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 nicall y p ossi ble, t he str uct ural 
i nte grity of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless 
pre pr oce d ure test fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o mal y 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 in a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b o ut pre g na nc y  o utc o mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n;

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 AEs. 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). I n 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 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 0
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 x p os ure d uri n g breastfee di n g occ urs if: 
A fe male is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o st u d y  
i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of e n vir o n me ntal e x p os ure d uri n g 
breastfee di n g is a fe male fa mil y  me m ber or healt hcare pr o vi der w h o re p orts t hat s he is 
breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n.  
T he i n vesti gat or m ust re p ort e x p os ure d uri n g breastfee di n g t o Pfizer Safet y  wit hi n 2 4 h o urs 
of t he i n vesti gat or’s a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he 
i nf or mati o n m ust be re p orte d usi n g t he C T S A E Re p ort F or m. W he n e x p os ure d uri n g 
breastfee di n g occ urs i n t he setti n g of e n vi r 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 C T S A E Re p ort F or m is mai ntai ne d i n t he 
i n vesti gat or site file.
A n e x p os u re d uri n g breastfee di n g 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 wit h 
a ut h orize d use. B ut 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 x p os ure d uri n g breastfee di n g.
8. 4. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety wit hi n 
2 4 h o urs of t he i n vesti gat or’s a ware ness usi n g t he C T S A E Re p ort F or m re gar dless of
w het her t here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure 
d oes n ot pertai n t o a partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a 
C R F; b ut a c o p y of t he c o m plete d C T S A E Re p ort F or m m ust be 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 Es 
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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 1
8. 4. 8. 1. L ac k of Effic ac y
N ot a p plica ble.
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 .
E x p os u res t o t he st u d y i nter ve nti o n u n der st u d y m a y occ ur i n cli nical trial setti n gs, s uc h as 
me dicati o n err ors.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E Re p ort 
F or m t o Pfizer S afet y Wit hi n 
2 4 H o urs of A w are ness
Me dicati o n err ors 
All (re gar dless
of w het her 
ass ociate d wit h a n A E)
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 .
S uc h me dicati o n err ors occ urri n g t o a st u d y partici pa nt are t o be ca pt ure d o n t he me dicati o n 
err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
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 .
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, t he me dicati o n err or is rec or de d o n t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o nseri o us, are rec or de d o n t he A E pa ge of t he 
C R F. 
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4
h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
8. 5. P h ar m ac o ki netics 
Bl o o d sa m ples will be c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of mi daz ola m, 
1 -h y dr o x y mi daz ola m, o me praz ole, 5 -h y dr o x y o m e praz ole, L E, E E , P F -0 7 0 8 1 5 3 2 , a n d 
se ma gl uti de as s pecifie d i n t he S o A .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 2
T he act ual ti mes ma y  c ha n ge, b ut t he n u m ber of sa m ples will remai n t he sa me.  All eff orts 
will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g.  C ollecti o n of 
sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d wit hi n 
1 0 % of t he n o mi nal ti me relati ve t o d osi n g ( e g, wit hi n 6 mi n utes of a 6 0 - mi n ute sa m ple) will 
n ot be ca pt ure d as a pr ot oc ol de viati o n, if 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, if 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 c ollecte d f or a nal yses of st u d y i nter ve nti o n c o nce ntrati o n ma y als o be use d t o 
e val uate safet y or efficac y as pects relate d t o c o ncer ns arisi n g d uri n g or after t he st u d y , f or 
meta b olite i de ntificati o n a n d/ or e val uati o n of t he bi oa nal y tical met h o d, or f or ot her i nter nal 
e x pl orat or y p ur p oses.
Sa m ples c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of st u d y  i nter ve nti o n will be 
a nal yz e d usi n g a va li date d a nalyt 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.
Ge netic a nal ys es will n ot be perf or me d o n t hese 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.
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 
inte grit y h as bee n c o m pr o mise d. A n y  de viati o n fr o m t he s pecifie d sa m ple ha n dli n g 
pr oce d ure res ulti n g i n c o m pr o mise d sa m ple i nte grit y, will be c o nsi dere d a pr ot oc ol 
de viati o n.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt.  T he I R B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit o ri n g sc he me or 
a me n d me nt of t he I C D.
I nstr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he 
la b orat or y ma n ual or b y t he s p o ns or.  T he act ual date a n d ti me ( 2 4 -h o ur cl oc k ti me) of eac h 
sa m ple will be rec or de d.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 3
8. 5. 1. P K of Mi d az ol a m a n d 1- h y dr o x y mi d az ol a m
Sa m ples will be use d t o e val uate t he P K of mi daz ola m a n d 1 -h y dr o x y mi daz ola m.  F or 
C o h ort 1, b l o o d sa m ples of a p pr o xi matel y 4 m L, t o pr o vi de 2 ali q u ots of plas ma v ol u me of 
a p pr o xi matel y 0. 8 m L  eac h, will be c ollecte d i nt o a p pr o priatel y la bele d t u bes c o ntai ni n g 
K 2E D T A f or meas ure me nt of plas ma c o nce ntrati o ns of mi daz ola m a n d 1 -h y dr o x y mi daz ola m 
as s pecifie d i n t he S o A .  F or C o h ort 2, bl o o d sa m ples of a p pr o xi matel y  5 m L, t o pr o vi de
2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  0. 8 m L  eac h will be c ollecte d i nt o 
a p pr o priatel y la bele d t u bes c o ntai ni n g K 2E D T A f or meas ure me nt of plas ma c o nce ntrati o ns 
of mi daz ola m a n d 1- h y dr o x y mi daz ola m as s pecifie d i n t he S o A . 
8. 5. 2. P K of O me pr az ole a n d 5 -h y dr o x y o me pr az ole
Sa m ples will be use d t o e val uate t he P K of o me praz ole a n d 5 -h y dr o x y o me praz ole .  Bl o o d 
sa m ples of a p pr o xi matel y 2 m L , t o pr o vi de 2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  
0. 4 m L  eac h, will be c ollecte d i nt o a p pr o priately la bele d t u bes c o n tai ni n g K2E D T A f or 
meas ure me nt of plas ma c o nce ntrati o ns of o me praz ole a n d 5 -h y dr o x y o me praz ole as s pecifie d 
i n t he S o A .  
8. 5. 3. P K of Le v o n or gestrel
Sa m ples will be use d t o e val uate t he P K of L E .  Bl o o d sa m ples of a p pr o xi matel y 6 m L , t o 
pr o vi de 2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  1. 2 m L  eac h, will be c ollecte d i nt o 
a p pr o priatel y la bele d t u bes c o ntai ni n g K 2E D T A f or meas ure me nt of plas ma c o nce ntrati o ns 
of L E as s pecifie d i n t he S o A .  
8. 5. 4. P K of Et hi n yl Estr a di ol
Sa m ples will be use d t o e val uate t he P K of E E .  Bl o o d sa m ples of a p pr o xi matel y 6 m L, t o 
pr o vi de 2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  1. 2 m L  eac h, will be c ollecte d i nt o 
a p pr o priatel y la bele d t u bes c o ntai ni n g K 2E D T A f or meas ure me nt of plas ma c o nc e ntrati o ns 
of E E as s pecifie d i n t he S o A .  
8. 5. 5. P K of P F - 0 7 0 8 1 5 3 2
Sa m ples will be use d t o e val uate t he P K of P F -0 7 0 8 1 5 3 2 .  Bl o o d sa m ples of a p pr o xi matel y 
2 m L , t o pr o vi de 2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  0. 3 m L  eac h, will be
c ollecte d i nt o a p pr o priatel y  la bele d t u bes c o ntai ni n g K2E D T A f or meas ure me nt of plas ma 
c o nce ntrati o ns of P F -0 7 0 8 1 5 3 2 as s pecifie d i n t he S o A .  
8. 5. 6. P K of S e m a gl uti de
Sa m ples will be use d t o e val uate t he P K of se ma gl uti de.  Bl o o d sa m ples of a p pr o xi matel y  6
m L , t o pr o vi de 2 ali q u ots of plas ma v ol u me of a p pr o xi matel y  1. 2 m L  eac h, will be c ollecte d 
i nt o a p pr o priately la bele d t u bes c o ntai ni n g K 2E D T A f or meas ure me nt of plas ma 
c o nce ntrati o ns of se ma gl uti de as s pecifie d i n t he S o A .  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 4
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
Ge netics (s pecifie d a nal yses) are n ot e val uate d i n t his st u d y .
See 
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 orat or y ma n ual.
8. 7. Bi o m ar kers
T he f oll o wi n g sa m ples f or bi o mar ker researc h are re q uire d a n d will be c ollecte d fr o m all 
partici pa nts i n t his st u d y  as s pecifie d i n t he S o A .
8. 7. 1. S pecifie d Pr otei n Rese arc h
8. 7. 2. 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. 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
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 5
8. 7. 5. Pl as m a f or A n al ysis of 4 -h y dr o x yc h olester ol/c h olester ol
Bl o o d sa m ples of a p pr o xi matel y  4 m L, t o pr o vi de 2 ali q u ots of plas ma v ol u me of 
a p pr o xi matel y 0. 8 m L  eac h, will be c ollecte d i nt o a p pr o priatel y la bele d t u bes c o ntai ni n g 
K 2E D T A f or t he a nalys is of 4-h y dr o x yc h olester ol a n d c h olester ol at ti mes s pecifie d i n t he 
S o A .  Instr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will b e pr o vi de d i n 
t he la b orat or y ma n ual.
Sa m ples c ollecte d f or a nal y ses of 4-h y dr o x yc h olester ol/c h olester ol plas ma c o nce ntrati o n 
ma y  als o be use d t o e val uate safet y as pects or efficac y 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.
8. 8. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y.
8. 9. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n an 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 a S A P, w hic h will be mai ntai ne d by 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; ho we ver, a n y maj or 
m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot heses
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 ose s of a nal ysis, t he f oll o wi n g a nal ys is sets are defi ne d:
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 6
P artici p a nt A n al ysis Set
Descri pti o n
E nr olle d / Ra n d o ml y 
assi g ne d t o st u d y 
i nter ve nti o n
" E nr olle d" mea ns a partici pa nt's a gree me nt t o partici pate i n a 
cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess. 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 dy, 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 n r olle d, u nless 
ot her wise s pecifie d b y t he pr ot oc ol. A partici pa nt will be 
c o nsi dere d e nr olle d if t he i nf or me d c o nse nt is n ot wit h dra w n 
pri or t o partici pati n g i n a n y  st u d y acti vit y after scree ni n g . 
Safet y
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nterve 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.
P K C o nce ntrati o n Set
T he P K c o nce ntrati o n p o p ulati o n is defi ne d as all partici pa nts 
w h o recei ve d at least 1 d ose of mi daz ola m , o me praz ole, a n 
oral c o ntrace pti ve , an d/ or P F - 0 7 0 8 1 5 3 2 a n d i n w h o m at least 
1 plas ma c o nce ntrati o n val ue is re p orte d.
P K Para meter Set
T he P K para meter a nal ys is p o p ulati o n is defi ne d as all 
partici pa nts w h o recei ve d at least 1 d ose of mi daz ola m,
o me praz ole, a n oral c o ntrace pti ve, a n d/ or P F -0 7 0 8 1 5 3 2 a n d 
ha ve at least 1 of t he P K para meters of i nterest calc ulate d. 
S h o ul d v o miti n g occ ur after c oa d mi nistrati o n of mi daz ola m, 
o me praz ole, or t he oral c o ntrace pti ve wit h P F -0 7 0 8 1 5 3 2 , t he 
res ulti n g P K para meters fr o m t hat partici pa nt fr o m t he 
c orres p o n di n g p eri o d ma y be e xcl u de d, w here f urt her details 
will be pr o vi de d i n t he S A P .
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y a nalys es are p erf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data. 
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal y ses of t he pri mar y a n d sec o n dar y 
e n d p oi nts.
9. 3. 1. Ge ner al C o nsi der ati o ns
9. 3. 1. 1. Deri v ati o n of P h ar m ac o ki netic P ar a meters
T he plas ma P K para meters f or mi daz ola m, 1 -h y dr o x y mi daz ola m, o me praz ole, 
5 -h y dr o x y o me praz ole, L E a n d E E f oll o wi n g S D a d mi nistrati o n (eit her al o ne or d uri n g
c oa d mi nistrati o n wit h P F - 0 7 0 8 1 5 3 2 or se ma gl uti de [ mi daz ola m o nl y]) will be deri ve d fr o m 
t he c o nce ntrati o n-ti me pr ofiles as detailed i n Ta ble 1 2 bel o w .  T he plas ma P K para meters f or 
P F - 0 7 0 8 1 5 3 2 f oll o wi n g M D
a d mi nistrati o n will be deri ve d fr o m t he c o nce ntrati o n- ti me 
pr ofiles as detaile d i n Ta ble 1 3 bel o w. 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 7
Act ual P K sa m pli n g ti mes will be use d i n t he deri vati o n of P K para meters. I n t he case t hat 
act ual P K sa m pli n g ti mes are n ot a vaila ble, n o mi nal P K sa m pli n g t i me will be use d i n t he 
deri vati o n of P K para meters.
T a ble 1 2 . Pl as m a P K P ar a meters f or Mi d az ol a m, 1 -O H -Mi d az ol a m, O me pr az ole, 
5 -O H -O me pr az ole, L e v o n or gestrel a n d E t hi n yl Estr a di ol
P a r a m eter
Defi niti o n
M e t h o d of Deter mi n ati o n
A U C last
Area u n der t he plas ma 
c o nce ntrati o n-ti me pr ofile fr o m 
ti me zer o t o t he ti me of t he last 
q ua ntifia ble c o nce ntrati o n ( C last).
Li near/ L o g tra pez oi dal met h o d.
A U C i nf*
Area u n der t he plas ma 
c o nce ntrati o n-ti me pr ofile fr o m 
ti me zer o e xtra p olate d t o i nfi nite 
ti me.
A U C last + ( C last*/ k el), w here Clast* is 
t he pre dicte d plas ma c o nce ntrati o n 
at t he last q ua ntifia ble ti me p oi nt 
esti mate d fr o m t he l o g -li near 
re gressi o n a nal ysis.
C ma x
Ma xi m u m plas ma c o nce ntrati o n.
O bser ve d directl y fr o m data.
T ma x
Ti m e f or C ma x.
O bser ve d directl y fr o m data as ti me 
of first occ urre nce.
t1/ 2*
T er m i nal half-life.
L o g e( 2)/ kel,
w here k el is t he ter mi nal p hase rate 
c o nsta nt calc ulate d b y a li near 
re gressi o n of t he l o 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 oral cleara nce.
D ose/ A U C i nf.
V z/ F *
A p pare nt v ol u me of distri b uti o n.
D ose / (A U C i nf • kel). 
M R 
Mi daz ola m meta b olite/ pare nt 
rati o.
1- h y dr o x y mi daz ola m/ mi daz ola m
f or A U Ci nf, A U Clast, a n d Cma x
(a dj uste d t o acc o u nt f or differe nces 
i n m olec ular wei g ht).
M R
O m e praz ole meta b olite/ pare nt 
rati o.
5- h y dr o x y o m e praz ole/ o me praz ole 
f or A U Ci nf, A U Clast, a n d Cma x
(a dj uste d t o acc o u nt f or differe nces 
i n m olec ular wei g ht).
* as data per mit; C L/ F a n d V z/ F will n ot be calc ulate d f or 1-O H -mi daz ola m or 5 -O H -o m e praz ole
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 8
T a ble 1 3 .
Pl as m a P K P ar a meters f or P F - 0 7 0 8 1 5 3 2
P a r a m eter
Defi niti o n
M e t h o d of Deter m i n ati o n
A U C 2 4
Area u n der t he plas ma 
c o nce ntrati o n-ti me pr ofile fr o m 
ti me zer o t o ti me 2 4 h o urs.
A U C t (area u n der t he plas ma 
c o nce ntrati o n-ti me pr ofile w here 
t = 0 t o 2 4 h o urs) .
C ma x
Ma xi m u m plas ma c o nce ntrati o n 
o bser ve d fr o m ti me zer o t o 
2 4 h o urs .
O bser ve d directl y fr o m data .
T ma x
Ti m e f or C ma x.
O bser ve d directl y fr o m data as ti me 
of first occ urre nce .
A s i n gle tr o u g h c o nce ntrati o n sa m ple will be o btai ne d f or se ma gl uti de at 0 h o n Wee ks 5, 9, 1 3, a n d 1 7
d uri n g Peri o d 2 a n d pri or t o d osi n g i n Peri o d 3, Da y 1.  
9. 3. 2. St atistic al Met h o ds f or P h ar m ac o ki netic D at a
T he P K data f or mi daz ola m, 1 -h y dr o x y mi daz ola m , o me praz ole, 5 -h y dr o x y o me praz ole, L E, 
E E , a n d P F - 0 7 0 8 1 5 3 2 will be a nal yz e d a n d re p orte d se paratel y.
Plas ma c o nce ntrati o ns will be liste d a n d s u m marize d descri pti vel y b y P K sa m pli n g ti me a n d 
treat me nt ( d osi n g al o ne vs. c oa d mi nistrati o n or d ose b y  C o h ort of st u d y , as a p plica ble).
I n di vi d ual partici pa nt a n d me dia n pr ofiles of t he c o nce ntrati o n-ti me data will be pl otte d b y
treat me nt. F or s u m mar y statistics a n d me dia 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 f or plas ma sa m ples will be use d . 
Me dia n pr ofiles will be prese nte d o n bot h li near-li near 
a n d l o g-li near scales.
C o h ort 1
Nat ural l o g e-tra nsf or me d A U C i nf (as data per mit), A U Clast a n d C ma x of o me praz ole
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 will be a nal y ze d 
usi n g a mi xe d effect m o del wit h treat me nt as a fi xe d effect a n d partici pa nt as a ra n d o m 
effect.  Esti mates of t he a dj uste d mea n differe nces ( Test -refere nce) a n d c orres p o n di n g 
9 0 % CI s will be o btai ne d fr o m t he m o dels.  T he a dj uste d mea n di ffere 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 2 test treat me nts will be 
‘o me praz ole a n d P F -0 7 0 8 1 5 3 2 8 0 m g Q D’ ( Peri o d 4) a n d ‘ o me praz ole a n d P F - 0 7 0 8 1 5 3 2
2 6 0 m g Q D’ ( Peri o d 7), w hic h will be re p orte d se paratel y i n c o m paris o n t o t he refere nce 
treat me nt of ‘o me praz ole wit h o ut P F - 0 7 0 8 1 5 3 2’ ( Peri o d 1).  
Nat ural l o g e-tra nsf or me d A U Ci nf (as data per mit) of t he 5- h y r o xy o me praz ole/ o me pra z ole
rati os ( M R) a d mi nistere d wit h o ut P F- 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 will be 
a nal yz e d usi n g a mi xe d effect m o del wit h treat me nt as a fi xe d effect a n d partici pa nt as a 
ra n d o m effect.  Esti mates of t he a dj uste d mea n differe nces ( Test-refere nce) a n d 
c orres p o n di n g 9 0 % CIs will be o btai ne d fr o m t he m o dels.  T he a dj uste d mea n differe nces 
a n d 9 0 % CIs f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of 
a dj uste d ge o metric mea ns ( Test/ Refere nce) a n d 9 0 % CI s f or t he rati os.  T he 2 test treat me nts 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 9
will be ‘ o me praz ole a n d P F-0 7 0 8 1 5 3 2 8 0 m g Q D’ ( Peri o d 4) a n d ‘ o me praz ole a n d 
P F - 0 7 0 8 1 5 3 2 2 6 0 m g Q D’ ( Peri o d 7), w hic h will be re p orte d se parately i n c o m paris o n t o t he 
refere nce treat me nt of ‘ o me praz ole wit h o ut P F - 0 7 0 8 1 5 3 2’ ( Peri o d 1).
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 i n C o h ort 1 will be 
a nal yz e d a n d re p orte d se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or
o me praz ole .  T he 2 test treat me nts will be ‘ mi daz ola m a n d P F - 0 7 0 8 1 5 3 2 80 m g Q D’ 
( Peri o d 4 ) a n d ‘ mi daz ola m a n d P F - 0 7 0 8 1 5 3 2 2 6 0 m g Q D’ ( Peri o d 7 ), w hic h will be re p orte d 
se paratel y i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m wit h o ut P F - 0 7 0 8 1 5 3 2’ 
( Peri o d 1 ).
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F - 0 7 0 8 1 5 3 2 i n C o h ort 1 will be 
a nal yz e d a n d re p orte d se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or 
o me praz ole.  T he test treat me nt will be ‘ mi daz ola m al o ne f oll o wi n g disc o nti n uati o n of 
P F - 0 7 0 8 1 5 3 2’ ( Peri o d 9), w hic h will be re p orte d se paratel y i n c o m paris o n t o t he 2 refere nce 
treat me nts of ‘ mi daz ola m wit h o ut P F -0 7 0 8 1 5 3 2’ ( Peri o d 1) a n d ‘ mi daz ola m a n d 
P F - 0 7 0 8 1 5 3 2 2 6 0 m g Q D’ ( Peri o d 7).
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit) of t he 1-h y r o xy m i daz ola m/ mi daz ola m rati os 
a d mi nistere d wit h o ut P F - 0 7 0 8 1 5 3 2 or c oa d mi nistere d wit h P F -0 7 0 8 1 5 3 2 i n C o h ort 1 will be 
a nal yz e d a n d re p orte d se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or 
o me praz ole.  T he 2 test treat me nts will be ‘ mi daz ola m a n d P F-0 7 0 8 1 5 3 2 8 0 m g Q D’ 
( Peri o d 4) a n d ‘ mi d az ola m a n d P F- 0 7 0 8 1 5 3 2 2 6 0 m g Q D’ ( Peri o d 7), w hic h will be re p orte d 
se paratel y i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m wit h o ut P F-0 7 0 8 1 5 3 2’ 
( Peri o d 1).
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of L E a n d E E 
a d mi nistere d al o ne or c oa d mi nistere d wit h P F-0 7 0 8 1 5 3 2 will be a nal yz e d a n d re p orte d 
se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole.  F or L E, 
t he 2 test treat me nts will be ‘ L E a n d P F- 0 7 0 8 1 5 3 2 8 0 m g Q D’ ( Peri o d 5) a n d ‘ L E a n d 
P F - 0 7 0 8 1 5 3 2 2 6 0 m g Q D’ ( Peri o d 8), w hic h will be re p orte d se paratel y i n c o m paris o n t o t he 
refere nce treat me nt of ‘ L E al o ne’ ( Peri o d 2 ).  Si milarl y f or E E, t he 2 test treat me nts will be 
‘ E E a n d P F- 0 7 0 8 1 5 3 2 8 0 m g Q D’ ( Peri o d 5) a n d ‘ E E a n d P F -0 7 0 8 1 5 3 2 2 6 0 m g Q D’ 
( Peri o d 8), w hic h will be re p orte d se paratel y i n c o m paris o n t o t he refere nce treat me nt of ‘ E E 
al o ne’ ( Peri o d 2 ).
C o h ort 2
Nat ural l o g e-tra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d al o ne or c oa d mi nistere d wit h se ma gl uti de will be a nal y ze d a n d re p orte d 
se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole.  T he test 
treat me nt will be ‘ mi daz ola m a n d se ma gl uti de 2. 4 m g w ee kl y’ ( Peri o d 3) w hic h will be 
re p orte d se paratel y i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m al o ne’ ( Peri o d 1).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 0
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit), Cma x a n d A U C last of mi daz ola m 
a d mi nistere d wit h o ut se ma gl uti de or c oa d mi nistere d wit h se ma gl uti de will be a nal yz e d a n d 
re p orte d se parately usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole.  
T he test treat me nt will be ‘ mi daz ola m al o ne f oll o wi n g disc o nti n uati o n of se ma gl uti de’
( Peri o d 4 ), w hic h will be re p orte d se paratel y i n c o m paris o n t o t he 2 refere nce treat me nts of 
‘ mi daz ola m wit h o ut se ma gl uti de’ ( Peri o d 1) a n d ‘ mi daz ola m a n d se ma gl uti de 2. 4 m g 
wee kl y ’ ( Peri o d 3).
Nat ural l o g etra nsf or me d A U Ci nf (as data per mit) of t he 1-h y r o xy m i daz ola m/ mi daz ola m rati os 
a d mi nistere d al o ne or c oa d mi nistere d wit h se ma gl uti de will be a nal y ze d a n d re p orte d 
se paratel y usi n g t he sa me mi xe d effect m o del as descri be d a b o ve f or o me praz ole.  T he test 
treat me nt will be ‘ mi daz ola m a n d se ma gl uti de 2. 4 m g wee kly’ ( Peri o d 3) w hic h w ill be 
re p orte d se parately i n c o m paris o n t o t he refere nce treat me nt of ‘ mi daz ola m al o ne’ ( Peri o d 2 ).
If less t ha n 1 2 partici pa nts ha ve P K para meters relate d t o c oa d mi nistrati o n wit h 
P F - 0 7 0 8 1 5 3 2 2 60 m g Q D, t he a b o ve mi xe d effect m o dels ma y  a d diti o nall y/alter nati vely 
i ncl u de P K para meters fr o m t he ma xi m u m t olerate d d ose of P F - 0 7 0 8 1 5 3 2 (if a p plica ble), 
w here f urt her details will be i ncl u de d i n t he S A P.
T he a b o ve a n d ot her P K para meters f or mi daz ola m, 1 -h y dr o x y m i daz ola m, o me praz ole, 
5- h y dr o x y o me praz ole , L E a n d E E , a n d P K para meters f or P F - 0 7 0 8 1 5 3 2, will be se parately 
s u m marize d descri pti vel y by treat me nt.
If e val uate d, the plas ma 4 -h y dr o x y c h olester ol, c h olester ol a n d 
data will be s u m marize d 
descri pti vel y b y peri o d ( D a y 1 i n Peri o ds 1, 4, 7 a n d 9 i n C o h ort 1 a n d Da y 1 i n Peri o ds 1 , 3 
a n d 4 i n C o h ort 2). T he p las ma rati os of 4 -h y dr o x y c h olester ol/c h olester ol will als o be 
s u m marize d descri pti vel y b y  peri o d.  Perce nt c ha n ge f or t he 4 -h y dr o x y c h olester ol/
c h olester ol rati o s fr o m baseli ne ( Da y 1 Peri o d 1 i n C o h orts 1 a n d 2) will be re p orte d, a n d 
f urt her details will be i ncl u de d i n t he S A P.
9. 3. 3. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
A E s, b o d y  wei g ht a n d safet y la b orat or y data will be re vie we d a n d s u m marize d o n a n 
o n g oi n g basis d uri n g t he st u d y  t o e val uate t he safet y of partici pa nt s. Partici pa nts ma y  
u n der g o c ollecti o n of E C Gs, B P, a n d P R at t he discreti o n of t he i n vesti gat or.  A n y cli nical 
la b orat or y, E C G, B P, a n d P R 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 1
Me dica l hist or y a n d p h ysical e xa mi nati o n a n d ne ur ol o gical e xa mi nati o n i nf or mati o n, as 
a p plica ble, c ollecte d d uri n g t he 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 y sical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d d uri n g t he acti ve c ollecti o n peri o d will 
be ca pt ure d as A Es, if t h ose fi n di n gs meet t he defi niti o n of a n A E.  
Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as la b orat or y  
data, E C Gs , a n d vital si g ns , will be c o nsi dere d s o urce data, a n d will n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d.  De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.  
9. 3. 3. 1. Electr oc ar di o gr a m A n al yses
N ot a p plica ble.
9. 3. 4. Ot her A n al yse (s)
Tertiar y / E x pl orat or y a nal yses n ot i ncl u de d i n t he p har mac o ki netic or safety a nal ys es o utli ne d 
a b o ve will be d oc u me nte d i n t he S A P. 
9. 4. I nteri m A n al yses
N o f or mal i nteri m a nalys is will be c o n d ucte d f or t his st u d y.  As t his is a n o pe n-la bel st u dy, 
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 st u d y f or t he p ur p ose of 
safety assess me nt, facilitati n g P K m o deli n g, a n d/ or s u p p orti n g cli nical de vel o p me nt.
9. 5. S a m ple Size Deter mi n ati o n
A p pr o xi matel y  1 2 e val ua ble partici pa nts will c o m plete eac h c o h ort of t he st u d y .
A sa m ple size of 1 2 partici pa nts will pr o vi de 9 0 % CI s f or t he differe nce bet wee n treat me nts 
of ± 0. 2 4 9 1, ± 0. 2 4 8 a n d ± 0. 1 1 6 1 o n t he nat ural l o g scale f or A U Ci nf i n t he assess me nt of 
mi daz ola m, o me praz ole a n d L E or E E, res pecti vel y , wit h 8 0 % c o vera ge pr o ba bilit y. T he 
wi dt h of 9 0 % CI s f or differe nt esti mate d effects is prese nte d i n Ta ble 1 4 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 2
T a ble 1 4 . E x pecte d Wi dt hs of t he 9 0 % CIs ( wit h 8 0 % C o ver a ge Pr o b a bilit y) f or 
Differe nt P ossi ble Esti m ate d Effects a n d P ar a meters of I nterest
Refere nce
Esti m ate d Effect
( Test/ Refere nce)
A U C i nf
Pr o b a ble
9 0 % CI
Pr o b a ble
CI Wi dt h
Mi daz ola m
5 0 %
3 9 % - 6 4 %
2 5 %
7 5 %
5 8 % - 9 6 %
3 8 %
1 0 0 %
7 8 % - 1 2 8 %
5 0 %
1 2 5 %
9 7 % - 1 6 0 %
6 3 %
1 5 0 %
1 1 7 % - 1 9 2 %
7 5 %
2 0 0 %
1 5 6 % - 2 5 7 %
1 0 1 %
O m e praz ole
5 0 %
3 9 % - 6 4 %
2 5 %
7 5 %
5 8 % - 9 6 %
3 8 %
1 0 0 %
7 8 % - 1 2 8 %
5 0 %
1 2 5 %
9 7 % - 1 6 0 %
6 3 %
1 5 0 %
1 1 7 % - 1 9 2 %
7 5 %
2 0 0 %
1 5 6 % - 2 5 6 %
1 0 0 %
L E or E E
5 0 %
4 5 % - 5 6 %
1 1 %
7 5 %
6 7 % - 8 4 %
1 7 %
1 0 0 %
8 9 % -1 1 2 %
2 3 %
1 2 5 %
1 1 1 % - 1 4 0 %
2 9 %
1 5 0 %
1 3 4 % - 1 6 8 %
3 5 %
2 0 0 %
1 7 8 % - 2 2 5 %
4 7 %
T hese esti mates are base d o n data fr o m pre vi o us i nter nal D DI st u dies of mi daz ola m, 
o me praz ole, a n d a n oral c o ntrace pti ve c o ntai ni n g L E/ E E. T hese esti mates are base d o n t he 
ass u m pti o n t hat wit hi n -partici pa nt sta n dar d de viati o ns are 0. 2 9 4 a n d 0. 1 3 7 f or l n A U C i nf of 
mi daz ola m a n d L E or E E, res pecti vel y, as o btai ne d fr o m pre vi o us Pfizer st u dies i n o bese 
partici pa nts.  F or o me praz ole, t hese esti mates are base d o n a n ass u me d c o nser vati ve 
wit hi n -partici pa nt sta n dar d de viati o n of 0. 2 9 3 f or l n A U C i nf  i n o bese partici pa nts.
Partici pa nts w h o fail t o c o m plete t he st u d y  ma y be re place d at t he discreti o n of t he s p o ns or.
9. 6. D at a M o nit ori n g C o m mittee or Ot her I n de pe n de nt O versi g ht C o m mittee
T his st u d y  will n ot use a D M C.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 3
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S
1 0. 1. A p pe n di x 1: Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns
1 0. 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes , i ncl udi n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes ;

A p plica ble I C H G C P g ui deli nes ;

A p plica ble la ws a n d re g ulati o ns , i ncl u di n g a p plica ble pri vac y la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, S R S D(s) , a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or, s u b mitte d t o a n IR B/ E C 
b y  t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y  t he I R B/ E C bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o n e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n 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 (if a p plica ble), 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 (if a p plica ble), a n d all ot her a p plica ble l ocal 
re g ulati o ns.
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y.  
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 4
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr ote ct 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
I n vesti gat ors a n d s u bi n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate fi na ncial 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y  a ut h orities. I nvesti gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he st u d y a n d f or 
1 ye ar after c o m pleti o n of t he st u d y .
1 0. 1. 3. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or his/ her 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 st u d y  partici pa nt is f ull y i nf or me d a b o ut t he nat ure 
a n d o bjecti ves of t he st u d y, t he s hari n g of data relate d t o t he st u d y , a n d p ossi ble ris ks 
ass ociate d wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he 
pa rtici pa nt’s pers o nal data. 
T he partici pa nt m ust be i nf or me d t hat his/ her 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 p a nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y partici pa nt is f ull y i nf or me d a b o ut his or 
her ri g ht t o access a n d c orrect his or her 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 his or her pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C D.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 5
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 C D (s) d uri n g t heir 
partici pati o n i n t he st u d y .
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.
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 
disast er. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site will be res p o nsi ble 
f or deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g 
breac h n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, partici pa nts will be assi g ne d a si n gle, partici pa nt s pecific - n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt s pecific - c o de. T he st u d y  site will 
mai ntai n a c o nfi de ntial list of partici pa nt s w h o partici pate d i n t he st u d y, li n ki n g eac h 
partici pa nt ’s n u merical c o de t o his or her 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 nt s’ 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.
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 a D M C. 
1 0. 1. 6. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E u dra C T, a n d/ or 
w w w. pfizer.c o m, a n d ot her p u blic re gistries 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 a re re p orte d re gar dless of t he o utc o me of t he st u dy or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 6
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer 
s p o ns ore d- i nter ve nti o nal st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or 
efficac y of a pr o d uct, re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. 
T hese r es ults are s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h 
b y  U S la w.
E u dra C T
Pfizer p osts clinical trial r es ults o n E u dra C T f or Pfizer s p o ns ore d - i nter ve nti o nal st u dies i n 
acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y  E U re q uire me nts.
w w w. pfizer.c o m
Pfizer p osts p u blic discl os ure s y n o pses ( C S R s y n o pses i n w hic h a n y data t hat c o ul d be use d 
t o i de ntif y i n di vi d ual partici pa nts ha ve bee n re m o ve d) 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 .
D oc u me nts wit hi n mar keti n g a ut h orizati o n pac ka ges/s u b missi o ns
Pfizer c o m plies wit h t he E ur o pea n U ni o n P olic y  0 0 7 0, t he pr oacti ve p u blicati o n of cli nical 
data t o t he E M A we bsite. Cli nical data, u n der P hase 1 of t his p olic y , i ncl u des cli nical 
o ver vie ws, cli nical su m maries, C S Rs, a n d a p pe n dices c o ntai ni n g t he p r ot oc ol a n d p r ot oc ol 
a me n d me nts, sa m ple C R F s, a n d statistical met h o ds. Cli nical data, u n der P hase 2 of t his 
p olic y , i ncl u des t he p u blis hi n g of i n di vi d ual partici pa nt data. P olic y  0 0 7 0 a p plies t o ne w 
mar keti n g a ut h orizati o n a p plicati o ns s u b mitte d via t he ce ntrali ze d pr oce d ure si nce 
0 1 Ja n uar y 2 0 1 5 a n d a p plicati o ns f or li ne e xte nsi o ns a n d f or ne w i n dicati o ns s u b mitte d via 
t he ce ntralize d pr oce d ure si nce 01 J ul y  2 0 1 5.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o p atie 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 
2 4 m o nt hs after st u d y  c o m pletio n. Patie nt le vel - data will be a n o n y m ize d i n acc or da nce wit h 
a p plica ble pri vac y la ws a n d re g ulati o ns. C S Rs will ha ve pers o nall y i de ntifia ble i nf or mati o n 
re dacte 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 y ses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 7
1 0. 1. 7. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
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 ypte 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.
Q T L s are pre defi ne d para meters t hat are m o nit ore d d uri n g t he st u d y . I m p orta nt de viati o ns 
fr o m t he Q T Ls a n d a n y re me dial acti o ns ta ke n will be s u m marize d i n t he cli nical st u d y  
re p ort.
T he i n vesti gat or m ust per mit st u d y relate d- m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts. T his 
verificati o n m a 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 detai ls 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- mo nit ori n g), met h o ds, res p o nsi bilities, a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n a n d 
m o nit ori n g pla n mai ntai ne d a n d utilize d b y  t he s p o ns or or desi gnee .
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C D s, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y  be destr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y  be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 8
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 pera te 
wit h t he s p o ns or or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he 
i n vesti gat or site a n d i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
bet wee n t he st u d y data a n d t he partici pa nt's me dical rec or ds. T he i n vesti gat or will pr o m ptl y  
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt. Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he in vesti gat or will pr o vi de t he s p o ns or or its 
a ge nts wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs.
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 grit y 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.
I n t his st u dy, t he C R F will ser ve as t he s o urce d oc u me nt. A d oc u me nt m ust be a vaila ble at 
t he i n vesti gati ve site t hat i de ntifies t h ose data t hat will be rec or de d o n t he C R F a n d f or w hic h 
t he C R F will be t he s o urce d oc u me nt.
Defi niti o n of w hat c o nstit utes s o urce data a n d its ori gi n ca n be f o u n d i n t he cli nical 
m o nit ori n g pla n , w hic h is mai ntai ne d b y t he s p o ns or.
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.
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he C R F.
St u d y  m o nit ors will perf or m o n g oi n g s o urce data verificati o n 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 safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y  a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 9. 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 o n w hic h t he cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts.
T he first act of recr uit me nt is t he date of t he first partici pa nt’s first visit a n d will be t he st u d y  
start date.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 9
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 an 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. St u d y  sites will be cl ose d u p o n 
st u d y c o m pleti o n. A st u d y  site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y 
s u p plies ha ve bee n c ollecte d a n d a st u dy-site cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he s p o ns or 
or desi g nee/ C R O if re q ueste d t o d o s o b y  t he res p o nsi ble IR 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 early cl os ure of a st u d y site b y t he s p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or's pr oce d ures, or t he I C H G C P 
g ui deli n es;

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 Cs/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 ny 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 0. P u blic ati o n P olic y
T he res ults of t his st u d y  ma y be p u blis he d or prese nte d at scie ntific meeti n gs by t he 
i n vesti gat or after p u blicati o n of t he o verall st u d y res ults or 1 ye ar after t he e n d of t he st u d y 
( or st u d y ter mi nati o n), w hic he ver c o mes first. 
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns,
s uc h as sec o n dar y ma n uscri pts, a n d s u b mit s all ma n uscri pts or a bstracts t o t he s p o ns or 
3 0 da y s bef ore s u b missi o n. T his all o ws t he s p o ns or t o pr otect pr o prietar y  i nf or mati o n a n d t o 
pr o vi de c o m me nts , a n d t he i n vesti gat or will, o n re q uest, re m o ve a ny pre vi o usl y u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y- or Pfizer 
i nter ve nti o n- relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or will c o m pl y wit h rec o g nize d et hical 
sta n dar ds c o ncer ni n g p u 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 0
T he s p o ns or will c o m pl y  wit h t he re q uire me nts f or p u blicati o n of t he o verall st u d y res ults 
c o veri n g all i n vesti gat or sites. I n acc or da nce wit h sta n dar d e dit orial a n d et hical practice, t he 
s p o ns or will s u p p ort p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as 
i n di vi d ual site data. I n t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y m ut ual 
a gree me nt.
A ut h ors hi p of p u blicati o ns f or t he o verall st u d y  res ults will be deter mi ne d b y m ut ual 
a gree me nt a n d i n li ne wit h Inter nati o nal C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p 
re q uire me nts. 
If p u blicati o n is a d dresse d i n t he cli nical st u d y a gree me nt, t he p u blicati o n p olic y set o ut i n 
t his secti o n will n ot a p pl y.
1 0. 1. 1 1. S p o ns or’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y  q ualifie d me dical pers o n nel 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 S T o D s yste m. 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel f or st u d y relate d me dical 
q uesti o ns or pr o ble ms, 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, a n d ( d) Pfizer C all C e nter n u m ber.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he i n vesti gat or, site staff, a n d st u d y  tea m. T he E C C is 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 d y o nl y , as a mea ns of reac hi n g t he i n vesti gat or 
or site staff relate d t o t he care of a partici pa nt. T he Pfizer Call Ce nter n u m ber s h o ul d o nl y  be 
use d w he n t he i n vesti gat or a n d site staff ca n n ot be reac he d. T he Pfize r Call Ce nter n u m ber 
is n ot i nte n de d f or use by t he partici pa nt directl y; if a partici pa nt calls t hat n u m ber directl y, 
he or s he will be directe d bac k t o t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 1
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y  res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y, or as deri ve d 
fr o m calc ulate d val ues. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y iss ues.
T a ble 1 5 . Pr ot oc ol -Re q uire d S afet y L a b or at or y Assess me nts
He m at ol o g y
C he mi str y
Uri n al ysis
Ot her
He m o gl o bi n
He mat ocrit
R B C c o u nt
M C V
M C H
M C H C
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils ( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( Abs)
B U N 
Creati ni ne
e G F R
C y stati n- C
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
Direct bilir u bi n
I n direct bilir u bi n
G G T
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
Uri nal ysis:

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

Ur o bili n o ge n

Uri ne bilir u bi n

Micr osc o p y a
H b A 1c
Ser u m pre g na nc y test 
(-h C G) b
Li pi d pa nel:

T otal c h olester ol

Direct L D L - C

H D L - C

Tri gl yceri des
T S H
Free T 4
Calcit o ni n
A m ylase
Li pase
Ser u m T B A
S A R S -C o V - 2 test
Uri ne dr u g scree ni n g c
Scree ni n g o nl y:
F S H d
C- pe pti de (fasti n g)
HI V
H B s A gH C V A b
H C V R N A
A d diti o n al Tests ( Nee de d 
f or H y’s L a w)
A S T, A L T (re peat)
T otal bilir u bi n (re peat)
Al b u mi n (re peat)
Al kali ne p h os p hatase 
(re peat)
Direct bilir u bi n (re peat)
I n direct bilir u bi n (re peat)
C K
G G T (re peat)
P T /I N R
T otal bile aci ds (re peat)
Aceta mi n o p he n dr u g a n d/ or 
pr otei n a d d uct le vels
a.
O nl y if uri ne di pstic k is p ositi ve f or bl o o d, pr otei n, nitrites or le u k oc yte esterase.
b.
Ser u m -h C G f or all W O C B P.
c.
T he mi ni m u m re q uire me nt f or dr u g scree ni n g i ncl u des c ocai ne, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot hers are site a n d st u d y s pecific).  At scree ni n g, Peri o d 1 Da y -1a n d at t he 
discreti o n of t he i n vesti gat or.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 2
d .
F or c o nfir mati o n of p ost me n o pa usal stat us o nl y. 
T he i n vesti gat or m ust re vie w t he la b orat or y re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical safety la b orat or y  
meas ure me nts at baseli ne a n d at all ti mes after d ose a d mi nistrati o n ma y  be retai ne d a n d 
st ore d f or t he d urati o n of t he st u d y. U p o n c o m pleti o n of t he st u d y , t hese retai ne d safety 
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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 3
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 wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) 
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 nically 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 la b orat or y  test 
res ults t hat meet a ny 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 ny pr ot oc ol -s pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal 
c o nc o mita nt dr u g treat me nt, or ot her t hera p y.

E xacer bati o n of a c hr o nic or i nter mitte nt pree xisti n g c o n diti o n, i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o n detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n , e ve n 
t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g - i nteracti o n.

S i g ns, s ym 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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 4
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 udie d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is t he A E.

Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s oci al a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).

A ntici pate d d a 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 ys icia 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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 5
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 bi lit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, 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, is c o nsi dere d seri o us.  
g.
T he e ve nt ma y  be s us pecte d fr o m cli nical sy m pt o ms or la b orat or y  fi n di n gs i n dicati n g 
a n i nfecti o n i n a partici pa nt e x p ose d t o a P fizer 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 yn o n y m o us. T hese cases are 
c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y p har mac o vi gila nce 
pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as pr o d uct defects, if 
a p pr o priate.
h.
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 part ici pa nt or ma y re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y  be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt 
i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 6
1 0. 3. 3. Rec or di n g / Re p orti n g a n d F oll o w - Up of A E s a n d/ or S A E s D uri n g t he A cti 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 o n t he C T S A E Re p ort F or m t o Pfizer Safet y t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; 
( 2) n o nseri o us A Es; a n d ( 3) e x p os ure t o t he st u d y i nter ve nti o n u n der st u d y d uri n g 
pre g na nc y  or breastfee di n g, a n d occ u pati o nal e x p os ure. 
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot 
t he sa me as t he A E pa ge of t he C R F. W he n t he sa me data are c ollecte d, t he f or ms m ust be 
c o m plete d i n a c o nsiste nt ma n ner. A Es s h o ul d be rec or de d usi n g c o ncise me dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
S A E
All
All
N o nseri o us A E
All
N o ne
E x p os ure t o t he st u d y 
i nter ve nti o n u n der st u d y 
d uri n g pre g na nc y  or 
breastfee di n g
All A Es/ S A Es ass ociate d 
wit h e x p os ure d uri n g 
pre g na nc y  or breastfee di n g
N ote: I nsta nces of E D P or 
E D B n ot ass ociate d wit h a n 
A E or S A E are n ot ca pt ure d 
i n t he C R F.
All i nsta nces of E D P are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) .*
All i nsta nces of E D B are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E). * *
E n vir o n me ntal or 
occ u pati o nal e x p os ure t o 
t he pr o d uct u n der st u dy 
t o a n o n-partici pa nt ( n ot 
i n v ol vi n g E D P or E D B).
N o ne.  E x p os ure t o a st u d y 
n o n - partici pa nt is n ot 
c ollecte d o n t he C R F.
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
re p orte d. * * *
*
E D P ( wit h or wit h o ut a n ass ociate d A E or S A E): a n y pre g na nc y i nf or mati o n is re p orte d t o Pfizer 
Safet y usi n g 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; if t he E D P is ass ociate d w it h a n 
S A E, t he n t he 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. 
* * E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m w hic h w o ul d als o i ncl u de details 
of a n y S A E t hat mi g ht be ass ociate d w it h t he E D B. 
* * * E n vir o n me nt al or Occ 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. 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 7

W he n a n A E
or S A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

T he i n vesti gat or will t he n rec or d all rele va nt A E or S A E i nf or mati o n i n t he C R F.

It is n ot acce pta ble f or t he in 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 .

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: As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y ; 
i nter ve nti o n n ot i n dicate d.

M o derate: Mi ni mal, l ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g 
a ge-a p pr o priate i nstr u me ntal A D L. I nstr u me ntal A D L refers t o pre pari n g meals, 
s h o p pi n g f or gr oceries or cl ot hes, usi n g t he tele p h o ne, ma na gi n g m o ne y, etc.

Se vere: Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life-t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g, li miti n g self 
care A D L. Self care A D L refers t o bat hi n g, dressi n g a n d u n dressi n g, fee di n g self, 
usi n g t he t oilet, ta ki n g me dicati o ns, a n d n ot be dri d de 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.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 8

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve y s 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 o ut.

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 his/ her asses s 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 
he/s he has re vie we d t he A E or S A E a n d has 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 m ati 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. B ut 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 his/ her 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 req uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or re p orti n g 
p ur p oses, as defi ne d b y t he s p o ns or . I n a d diti o n, if t he i n vesti gat or deter mi nes t hat 
a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or m ust rec or d t his 
ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort s uc h a n 
assess me nt i n t he de dicate d secti o n of t he C T S A E Re p ort F or m a n d i n acc or da nce 
wit h t he S A E re p orti n g re q uire me nts.
F oll o w - Up of A Es 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 b y 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 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 9

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 ny 
p ost m orte m fi n di n gs , i ncl u di n g hist o pat h ol o g y.

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs 
of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A Es
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D at a C ollecti o n T o ol

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 data c ollecti o n t o ol.

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 data 
c ollecti o n t o ol (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o u rs.

T he site will e nter t he S A E data i nt o t he electr o nic s y ste m 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 data c ollecti o n t o ol will 
be ta ke n off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves u p date d 
data o n a pre vi o usl y  re p orte d S A E after t he electr o nic data c ollecti o n t o ol 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 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 t he preferre d met h o d 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, 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 b y 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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 0
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
Males will n ot partici pate i n t his st u d y . 
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
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 at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o ns bel o w i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d usi n g a c o ntrace pti ve met h o d t hat is hi g hl y effecti ve ( wit h a fail ure 
rate of < 1 % per year), prefera bl y wit h l o w user de pe n de nc y , as descri be d bel o w 
d uri n g t he i nter ve nti o n peri o d a n d f or at least 2 8 da y s after t he last d ose of st u d y  
i nter ve nti o n, w hic h c orres p o n ds t o t he ti me nee de d t o eli mi nate a n y re pr o d ucti ve 
safety ris k of t he st u d y i nter ve nti o n(s).  T he i n vesti gat or s h o ul d e val uate t he 
effecti ve ness of t he c o ntrace pti v e met h o d i n relati o ns hi p t o t he first d ose of st u d y  
i nter ve nti o n.

Is a W O C B P a n d usi n g a c o ntrace pti ve met h o d t hat is hi g hl y effecti ve ( wit h a fail ure 
rate of < 1 % per year), wit h hi g h user de pe n de nc y, as descri be d bel o w d uri n g t he 
i nter ve nti o n peri o d a n d for at least 2 8 da y s after t he last d ose of st u d y i nter ve nti o n, 
w hic h c orres p o n ds t o t he ti me nee de d t o eli mi nate a n y  re pr o d ucti ve safety ris k of t he 
st u d y i nter ve nti o n(s).  I n a d diti o n, a sec o n d effecti ve met h o d of c o ntrace pti o n, as 
descri be d bel o w, m ust b e use d.  T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of 
t he c o ntrace pti ve met h o d i n relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n 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).
If fertilit y is u nclear (e g, a me n orr hea i n a d olesce nts or at hletes) a n d a me nstr ual c y cle 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 m ale wit h 1 of t he f oll o wi n g: 
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 1

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a n alter nate 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 d y 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 his t 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 d y.
2.
P ost me n o pa usal fe male.

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use.  In a d diti o n, a

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. 
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 vail a 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.
Hi g hl y Effecti ve Met h o ds T h at H a ve L o w User De pe n de nc y 
1.
I ntra uteri ne de vice.
2.
Bilateral t u bal occl usi o n.
3.
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 n o n h or m o nal .

N o n h or m o nal c o ntrace pti o n s h o ul d be use d.  T he s per mat o ge nesis c y cle is 
a p pr o xi matel y 9 0 d a y s.
4.  
Hi g hl y Effecti ve Met h o ds T h at Are User De pe n de nt 
Se x ual a bsti ne nce.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 2

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.
O ne of t he f oll o wi n g effecti ve barrie r met h o ds m ust be use d i n a d diti o n t o t he hi g hly 
effecti ve met h o ds liste d a b o ve t hat are user de pe n de nt:

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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 3
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 4
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o ns a n d F oll o w- U p Assess me nts
P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y  b ut a da pt 
are ter me d “a da pt ors.” I n s o me partici pa nt s, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me. T hese partici pa nt s fail t o a da pt a n d t heref ore are 
"s usce pti ble" t o pr o gressi ve a n d seri o us li ver i nj ur y, c o m m o nl y 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 s e veral da ys or wee ks. T he i ncrease i n T Bili t y picall 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, by t he ti me T Bili 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 e it her A S T O R A L T i n a d diti o n t o T Bili 
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 y s be c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all 
ot her p ossi ble ca uses of li ver i nj ur y ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt ’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nt s w 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 Bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A LT val ues > 3 × U L N A N D a T Bili val ue 
> 2 × U L N wit h n o e vi de nce of he m ol ys is 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 Bili 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 Bili a b o ve t he n or mal ra n ge: T Bili le vel i ncrease d fr o m 
baseli ne val ue b y a n a m o u nt of at least 1 × U L N o r if t he val ue reac hes 
> 3 × U L N ( w hic he ver is s maller).
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 5
Rises i n A S T/ A L T a n d T Bili 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. 
T he par tici 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 Bili 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, T B A, 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 
d ra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or f urt her 
testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal yses 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 b y 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 , 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 Bili 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 D I 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 ul ts of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 6
1 0. 7. A p pe n di x 7: Ki d ne y S afet y M o nit ori n g G ui deli nes
1 0. 7. 1. L a b or at or y Assess me nt of C h a n ge i n Ki d ne y F u ncti o n a n d Detecti o n of Ki d ne y 
I nj ur y
Sta n dar d ki d ne y  safet y m o nit ori n g re q uires assess me nt of baseli ne a n d p ost baseli ne ser u m 
creati ni ne ( Scr meas ure me nt t o e G F R [ Scr- base d e G F R] or [e Cr Cl]). Baseli ne a n d 
p ost baseli ne Sc y s ma kes it feasi ble t o disti n g uis h A KI fr o m ot her ca uses of Scr i ncrease. If 
Scr i ncrease is c o nfir me d after baseli ne, t he n refle x meas ure me nt of Sc y s is i n dicate d t o 
esti mate t he c o m bi ne d Scr-S c y s e G F R calc ulati o n (f or a d ults o nly).
Re gar dless of w het her ki d ne y  f u ncti o n m o nit ori n g tests are re q uire d as a r o uti ne safety 
m o ni t ori n g pr oce d ure i n t he st u d y, if t he i n vesti gat or or s p o ns or dee ms it necessar y t o f urt her 
assess ki d ne y safet y a n d q ua ntif y ki d ne y f u ncti o n, t he n t hese test res ults s h o ul d be ma na ge d 
a n d f oll o we d per sta n dar d of care.
1 0. 7. 2. A ge- S pecific Ki d ne y F u ncti o n C alc ul a ti 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
2 0 2 1 C K D -
E PI 
Scr O nl y
Scr
( 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/ 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/ 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/ 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/ 0. 9) -1. 2 0 0 × ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI 
Scr- Sc ys 
C o m bi ne d
Scr
( 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/ 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/ 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/ 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/ 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/ 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/ 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/ 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/ 0. 9) -0. 5 4 4 × ( Sc ys/ 0. 8) -0. 7 7 8 × ( 0. 9 9 6 1) A ge
I n ker L A et al. N E n gl J Me d. 2 0 2 1; 3 8 5: 1 7 3 7- 4 9.
1 0. 7. 3. A d verse E ve nt Gr a di n g f or Ki d ne y S afet y L a b or at or y A b n or m alities
A E gra di n g f or decli ne i n ki d ne y  f u ncti o n (ie, e G F R or e Cr Cl) will be acc or di n g t o K DI G O 
criteria.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 7
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 ec.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 ms ec (a bs ol ute) or by ≥6 0 ms ec 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 ds’
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 ec.

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 left b u n dle b ra nc h b l oc k ( Q R S > 1 2 0 ms ec).

Ne w - onset ri g ht b u n dle b ra nc h b l oc k ( Q R S > 1 2 0 ms ec).

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 peri o ds 
of as ys t ole ≥3. 0 sec o n ds or a ny esca pe rate < 4 0 b p m, or wit h a n esca pe r h y t 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 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.

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) .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 8

Ve ntric ular r h y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (heart 
rate < 4 0 b p m), accelerate d i di o ve ntric ular r h y t 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 maker place me nt .

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n .

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he e n u merate d list of maj or e ve nts of p ote ntial cli nical c o ncer n 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 b orat 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 t o be re p orte d as A Es/ S AEs.
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 9
1 0. 9. A p pe n di x 9 A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y be use d i n t he pr ot oc ol.
A b bre vi ati o n
Ter m
A bs
a bs ol ute
A D L
acti vities of dail y li vi n g
A E
a d verse e ve nt
A KI
ac ute ki d ne y i nj ur y
A L T
ala ni ne a mi n otra nsferase
A M
bef ore n o o n
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c o nce ntrati o n -ti me c ur ve
A U C 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 zer o 
e xtra p olate d t o i nfi nite ti me
A U C last
area u n der t he plas ma c o nce ntrati o n-ti me pr ofile fr o m ti me zer o t o 
t he ti me of t he last q ua ntifia ble c o nce ntrati o n ( Clast)
A U C t
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile w here t = 0 t o 2 4 
h o urs
A U C ta u
area u n der t he plas ma c o nce ntrati o n-ti me pr ofile o ver t he d osi n g 
i nter val, ta u
A U C 2 4
area u n der t he plas ma c o nce ntrati o n-ti me pr ofile fr o m ti me zer o t o 
ti me 2 4 h o urs
A V
atri o ve ntric ular
B B S
Bi os peci me n Ba n ki n g S yste m
-h C G
b eta h u ma n c h ori o nic g o na d otr o pi n
B MI
b o d y  mass i n de x
B P
bl o o d press ure
b p m
beats per mi n ute
B U N
bl o o d urea nitr o ge n
C F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
C hr o nic Ki d ne y  Disease E pi de mi ol o g y C olla b orati o n
C L
cleara nce
C L / F
a p pare nt oral cleara nce
C last
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 L p
plas ma cleara nce
C ma x
ma xi m u m plas ma c o nce ntrati o n
C O 2
car b o n di o xi de ( bicar b o nate)
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C R F
case re p ort f or m
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 0
A b bre vi ati o n
Ter 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
C li nical S t u d y R e p ort
C -S S R S
C ol u m bia S uici de Se verit y  Rati n g Scale
C T
cli nical trial
% C V
perce nt c oefficie nt of variati o n 
C Y P
c yt oc hr o me P 4 5 0
D/ C
disc har ge
D DI
dr u g -dr u g i nteracti o n
DI LI
dr u g -i n d uce d li ver i nj ur y
D M C
D ata M o nit ori n g C o m mittee
E C
et hics c o m mittee
E C C
E mer ge nc y  C o ntact Car d
e Cr Cl
esti mate d creati ni ne cleara nce
E C G
electr ocar di o gra m
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 P
e x p os ure d uri n g pre g na nc y
E E
et hi n yl estra di ol
e G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
E 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 Cli nical Trials Data base
F S B G
fi n gerstic k bl o o d gl uc ose
F S H
f ollicle-sti m ulati n g h or m o ne
F/ U
f oll o w-u p
G C P
G o o d Cli nical Practice
G E R D
gastr oes o p ha geal refl u x disease
G G T
ga m ma -gl uta m y l tra nsferase
G L P -1 
gl uca g o n -li ke pe pti de 1 
G L P -1 R
gl uca g o n -li ke pe pti de 1 rece pt or 
H A E
h y p o gl yc e mic a d verse e ve nt
H b A 1c
he m o gl o bi n A 1c
H Bs A g 
he patitis B s urface a nti ge n
H C V
h e patitis C vir us
H C V A b
he patitis C a nti b o d y
H D L -C
hi g h -de nsit y li p o pr otei n c h olester ol
He p
he patitis
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 1
A b bre vi ati o n
Ter m
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 L
I nterle u ki n
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 
i n vesti gati o nal pr o d uct 
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I RB
I nstit uti o nal Re vie w B oar d
I V
intra ve n o us (ly)
K DI G O
Ki d ne y  Disease: Im pr o vi n g Gl o bal O utc o mes
k el
first-or der eli mi nati o n rate c o nsta nt
K 2E D T A
di p otassi u m et h y le ne dia mi netetraacetic aci d 
L B B B
left b u n dle bra nc h bl oc k
L D L -C
l o w de nsit y li p o pr otei n c h olester ol
L E
le v o n or gestrel
L F T
li ver f u ncti o n test
L L N
L o wer li mit of n or mal
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M D
m ulti ple d ose
M D Z
mi daz ola m
M E N 2
m ulti ple e n d ocri ne ne o plasia s y n dr o me t y pe 2 
M H P
me ntal healt h pr ofessi o nal
M R
meta b olite t o pare nt rati o
m R N A
messe n ger ri b o n ucleic aci d
M T C
me d ullar y  t h yr oi d carci n o ma
N/ A
n ot a p plica ble
N O A E L
n o o bser ve d a d verse effect le vel
O A T P
or ga nic a ni o n tra ns p orti n g p ol y pe pti des
O C
oral c o ntrace pti ve
O H
h y dr o x y
O M P
o me praz ole
P B P K
p h y si ol o gically base d p har mac o ki netics
P C R
p ol y merase c hai n reacti o n
p H
p ote ntial of h y dr o ge n
P H Q -9
Patie nt Healt h Q uesti o n naire -9
P K
p har mac o ki netic(s)
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 2
A b bre vi ati o n
Ter m
P M
p ost -me n o pa usal
P R
p ulse rate
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q D
o nce dail y
Q Tc
c orrecte d Q T
Q Tc F
c orrecte d Q T ( Fri dericia met h o d)
q ual
q ualitati ve
Q T L
q ualit y  t olera nce li mits
R A
rhe u mat oi d art hritis
R B C
re d bl o o d cell
R S E
Relati ve Sta n dar d Err or
S A E
seri o us a d verse e ve nt
S A P
S tatistical A nal y sis P la n
S A R S -C o V -2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
Scr
ser u m creati ni ne
Sc y s
ser u m c ystati n C
S D
si n gle d ose; sta n dar d de viati o n
SI B
S uici dal I deati o n a n d Be ha vi or 
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 safety d oc u me nt
S T o D
st u d y tea m o n de ma n d
S T -T
S T se g me nt t o T wa ve c ha n ges o n 1 2 -lea d E C G
S SI D
st u d y-s pecific s u bject i de ntificati o n n u m be r
S U S A R
S us pecte d U ne x pecte d S eri o us A d verse R eacti o n
t1/ 2
ter mi nal eli mi nati o n half -life
T 2 D M
t ype 2 dia betes mellit us
T 4
t h yr o xi ne
T B A
t otal bile aci ds
T Bili
t otal bilir u bi n
T E A E
treat me nt e mer ge nt a d verse e ve nt 
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me t o C ma x
T N F -
t u m or necr osis fact or al p ha
T S H
t h yr oi d sti m ulati n g h or m o ne
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
U S PI
U nite d States P ac ka ge Insert 
V ss
v ol u me of distri b uti o n at stea d y  state
V z / F
a p pare nt v ol u me of distri b uti o n
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 3
A b bre vi ati o n
Ter m
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 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 4
1 1. R E F E R E N C E S
1.
Ørs k o v C, H olst JJ, K n u htse n S,et al. Gl uca g o n -li ke pe pti des G L P -1 a n d G L P - 2, 
pre dicte d pr o d ucts of t he gl uca g o n ge ne, are secrete d se paratel y fr o m pi g s mall i ntesti ne 
b ut n ot pa ncreas. E n d ocri n ol o g y . 1 9 8 6; 1 1 9( 4): 1 4 6 7 - 7 5.
2.
Kre y ma n n B, Willia ms G, G hatei M A, et al. Gl uca g o n -li ke pe pti de- 1 7-3 6: a 
p h y si ol o gical i ncreti n i n ma n. La ncet. 1 9 8 7; 2( 8 5 7 1): 1 3 0 0 - 3.
3.
Na uc k M A, Nie dereic h h olz U, Ettler R, et al. Gl uca g o n -li ke pe pti de 1 i n hi biti o n of 
gastric e m pt yi n g o ut wei g hs its i ns uli n otr o pic effects i n healt h y  h u ma ns. A m J P h ysi ol.
1 9 9 7; 2 7 3( 5): E 9 8 1 - 8.
4. 
Fli nt A, Ra be n A, Astr u p A, et al. Gl uca g o n -li ke pe pti de 1 pr o m otes satiety a n d 
s u p presses e ner g y i nta ke i n h u ma ns. J Cli n In vest . 1 9 9 8; 1 0 1( 3): 5 1 5 - 2 0.
5.
I DF Dia betes Atlas; 9 t h E diti o n . A vaila ble fr o m: I D F Dia betes Atlas.  Accesse d 
5 N o v 2 0 2 2.   
6.
Me n ke A, Casa gra n de S, Geiss L ,et al. Pre vale nce of a n d tre n ds i n d ia betes am o n g 
ad ults i n t he U nite d States , 1 9 8 8-2 0 1 2. J A M A . 2 0 1 5; 3 1 4( 1 0): 1 0 2 1 - 9.
7.
Stratt o n I M, A dler AI, Neil H A, et al. Ass ociati o n of gl yc ae mia wit h macr o vasc ular a n d 
micr o vasc ular c o m plicati o ns of t y pe 2 dia b etes ( U K P D S 3 5): pr os pecti ve o bser vati o nal 
st u d y. B MJ. 2 0 0 0; 3 2 1: 4 0 5 - 1 2.
8.
G u h D P, Z ha n g W, Ba ns bac k N, et al. T he i nci de nce of c o -m or bi dities relate d t o 
o besit y  a n d o ver wei g ht: a s yste matic re vie w a n d meta-a nal ys is. B M C P u blic Healt h.
2 0 0 9; 9: 8 8.
9.
Fle gal K M, K it B K, Or pa na H, et al. Ass ociati o n of all-ca use m ortalit y wit h o ver wei g ht 
a n d o besit y usi n g sta n dar d b o d y mass i n de x cate g ories: a sys te matic re vie w a n d 
meta -a nal ys is. J A M A. 2 0 1 3; 3 0 9( 1): 7 1 - 8 2.
1 0.
T he G B D 2 0 1 5 O besit y C olla b orat ors. Healt h effects of o ver wei g ht a n d o besit y  i n 
1 9 5 c o u ntries o ver 2 5 ye ars. N E n gl J Me d. 2 0 1 7; 3 7 7( 1): 1 3 - 2 7.
1 1.
A n ders o n J W, K o nz E C, Fre deric h R C, et al. L o n g -ter m wei g ht-l oss mai nte na nce: a 
meta -a nal ys is of U S st u dies. A m J Cli n N utr. 2 0 0 1; 7 4( 5): 5 7 9 - 8 4.
1 2.
Dr uc ker D J. T he asce n di n g G L P -1 r oa d fr o m cli nical safet y  t o re d ucti o n of 
car di o vasc ular c o m plicati o ns. Dia betes . 2 0 1 8; 6 7: 1 7 1 0 - 9. 
1 3.
Mi daz ola m I njecti o n, U S P. U nite d States Prescri bi n g I nf or mati o n.  Marc h 2 0 1 7. 
A vaila ble fr o m: 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 7/ 2 0 8 8 7 8 Ori g 1s 0 0 0l bl
Accesse d 3 N o v 2 0 2 2 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 5
1 4.
Pril osec ( o me praz ole) .  Hi g hli g hts of Prescri bi n g Inf or mati o n. Dece m ber 2 0 1 4. 
A vaila ble fr o m: 0 2 2 0 5 6s 0 1 7l bl 0 1 9 8 1 0s 1 0 1l bl. p df (f da. g o v).  Accesse d 5 N o v 2 0 2 2.  
1 5.
Le v o n or gestrel a n d Et hi n yl Estra di ol Ta blets U S P, 0. 1 5 m g / 0. 0 3 m g. U nite d States 
Prescri bi n g I nf or mati o n. Re vise d Ma y , 2 0 1 6. A vaila ble fr o m:
htt ps:// dail y me d. nl m. ni h. g o v/ dail y m e d/f da/f da Dr u g Xsl.cf m?seti d = 0 6 8 1 9 9a 9 -ef 2 2-
4 0 6 1 - b b 7 6-1ee 5 8f 7 2 6 0 1 8 . Accesse d 3 N o v 2 0 2 2.
1 6.
We g o v y ® (se ma gl uti de). U nite d States Prescri bi n g I nf or mati o n. J u ne 2 0 2 1.  A vaila ble 
fr o m: htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 2 1/ 2 1 5 2 5 6s 0 0 0l bl. p df . 
Accesse d 2 7 Oct 2 0 2 2.
1 7.
O Z E M PI C ® (se ma gl uti de). U nite d States Prescri bi n g I nf or mati o n. Ja n uar y 2 0 2 0.  
A vaila ble fr o m:
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 2 0/ 2 0 9 6 3 7s 0 0 3l bl   Accesse d 
3 N o v 2 0 2 2.
1 8.
T ur pa ult S, Bria n W, Va n H or n R, et al. P har mac o ki netic assess me nt of a fi ve- pr o be 
c oc ktail f or C Y Ps 1 A 2, 2 C 9, 2 C 1 9, 2 D 6 a n d 3 A. Br J Cli n P har mac ol. 
2 0 0 9; 6 8( 6): 9 2 8 - 3 5.
1 9.
R y u, J Y, Si n g, I S, S u n w o o I E, et al., De vel o p me nt of t he "I nje c oc ktail" f or hi g h -
t hr o u g h p ut e val uati o n of fi ve h u ma n c yt oc hr o me P 4 5 0 is of or ms i n viv o. Cli n P har mac ol 
T her . 2 0 0 7; 8 2( 5 ): 5 3 1- 4 0.
2 0.
Ka petas AJ, S or ic h  MJ, R o dri g ues A D, a n d R o wla n d A. G ui da n ce f or rifa m pi n a n d 
m i daz ola m d osi n g p r ot oc ols t o st u d y intesti nal a n d h e patic c yt oc hr o me P 4 5 0 ( C Y P) 
3 A 4 in d ucti o n a n d d e-i n d ucti o n.  T he A A P S J o ur nal . 2 0 1 9; 2 1( 7 8): 1- 1 1.
2 1.
Gree n blatt DJ, A ber net h y D R, L oc nis kar A, et.al. Effect of a ge, ge n der, a n d o besit y  o n
mi daz ola m ki netics. A nest hesi ol o g y . 1 9 8 4; 6 1( 1): 2 7- 3 5.
2 2.
Brill MJ , Die pstrate n J, va n R o n ge n A, et al.  I m pact of o besit y o n d r u g m eta b olis m a n d 
eli mi nati o n i n ad ults a n d chil dre n. Cli n P har mac o ki net . 2 0 1 2; 5 1( 5): 2 7 7 - 3 0 4.
2 3.
Desta Z, Z ha o X, S hi n J -G, a n d Fl oc k hart D A.  Cli nical si g nifica nce of t he cyt oc hr o me 
P 4 5 0 2 C 1 9 g e netic p ol y m or p his m .  Cli n P har mac o ki net . 2 0 0 2; 4 1( 1 2): 9 1 3 - 5 8.
2 4.
Tassa nee y a k ul W , Tassa nee y a k ul W, Va n na prasa ht S, a n d Ya maz oe Y.  F or mati o n of 
o me praz ole s ul p h o ne b ut n ot 5- h y dr o x y o m e praz ole is i n hi bite d b y gra pefr uit j uice.  Br J 
Cli n P har mac ol . 2 0 0 0; 4 9: 1 3 9 – 4 4.
2 5.
Der u n gs A, D o nzelli M, Ber ger B, et al. Effects of C yt oc hr o me P 4 5 0 in hi biti o n a n d 
i n d ucti o n o n t he p he n ot y pi n g m etrics of t he Basel coc ktail: A ra n d o mize d cr oss o ver 
st u d y.  Cli n P har mac o k i net. 2 0 1 6; 5 5: 7 9 – 9 1 .
0 9 0 1 7 7 e 1 9 b c 4 d 2f 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- N o v- 2 0 2 2 1 7: 5 2 ( G M T)

P F -0 7 0 8 1 5 3 2
Pr ot oc ol C 3 9 9 1 0 4 0
Fi nal Pr ot oc ol , x x N o ve m ber, 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 6
2 6.
F u r uta T, O has hi K, K o ba y as hi K, et al. Effects of clarit hr o m yci n o n t he meta b olis m of 
o me praz ole i n relati o n t o C Y P 2 C 1 9 g e n ot ype stat us i n h u ma ns . Cli n P har mac T her. 
1 9 9 9; 6 6( 3): 2 6 5 - 7 4.
2 7.
Nic h ols M, R o bi ns o n, G, B o u n ds, W, et al.  Effect of f o ur c o m bi ne d oral c o ntrace pti ves 
o n bl o o d press ure i n t he pill -free i nter val. C o ntrace pti o n. 1 9 9 3; 4 7: 3 6 7- 7 6.
2 8.
E der K, Baff y  N, Fal us A, a n d F ul o p A K . T he maj or i nfla m mat or y  me diat or 
i nterle u ki n-6 a n d o besit y. I nfla m m Res. 2 0 0 9,5 8: 7 2 7 – 3 6 .
2 9.
Ell ul u M S, Pat i ma h I, K haza’ai H, et al.  O besit y a n d i nfla m mati o n: t he li n ki n g 
mec ha nis m a n d t he c o m plicati o ns.  A rc h Me d Sci. 2 0 1 7; 1 3 ( 4): 8 5 1– 8 6 3 .
3 0.
Welle n K E a n d H ota misli gil G S . I nfla m mati o n, stress, a n d dia betes. J Cli n I n vest. 
2 0 0 5; 1 1 5( 5): 1 1 1 1 - 1 1 1 9.
3 1.
Tra y h ur n P a n d W o o d I S. Si g nalli n g r ole of a di p ose tiss ue: a di p o ki nes a n d 
i nfla m mati o n i n o besit y.  Bi oc he mical S ociet y  Tra nsacti o ns. 2 0 0 5; 3 3( 5):1 0 7 8 - 1 0 8 1.
3 2.
Mara nt os G, Das k ala kis N, Kar ka vitsas N, et al. C ha n ges i n m eta b olic p r ofile a n d 
a di p oi ns ular axis i n m or bi dl y  obese p re me n o pa usal fe males treate d wit h restricti ve 
b ariatric sur ger y . W orl d J S ur g. 2 0 1 1; 3 5: 2 0 2 2– 3 0.
3 3.
Bastar d J -P, Jar del C, Br uc kert E, et al. Ele vate d le vels of interle u ki n 6 are re d uce d i n 
ser u m a n d su bc uta ne o us adi p ose tiss ue of o bese w o me n after w ei g ht loss. J Cli n 
E n d ocri n ol o g y  Meta b olis m. 2 0 0 0; 8 5( 9):3 3 3 8 - 4 2.
3 4.
Br u u n J M, Ver dic h C, T o u br o S, et al. Ass ociati o n bet wee n meas ures of i ns uli n 
se nsiti vit y a n d circ ulati n g le vels of i nterle u ki n-8, i nterle u ki n - 6 a n d t u m or necr osis 
fact or- α. Effect of wei g ht l oss i n o bese me n.  E ur o pea n J E n d ocri n ol o g y. 
2 0 0 3 ; 14 8 : 5 3 5– 4 2 .
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