A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Escalating Oral Doses of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus
Phase: PHASE1
Conditions: Diabetes Mellitus Type 2
Sponsor: Pfizer

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1
A P H A S E 1, R A N D O MI Z E D, D O U B L E -B LI N D , S P O N S O R -O P E N, 
P L A C E B O -C O N T R O L L E D S T U D Y T O A S S E S S T H E S A F E T Y, T O L E R A BI LI T Y ,
A N D P H A R M A C O KI N E TI C S O F M U L TI P L E E S C A L A TI N G O R A L D O S E S O F 
P F -0 7 0 8 1 5 3 2 I N A D U L T P A R TI CI P A N T S WI T H T Y P E
2 DI A B E T E S M E L LI T U S
I n vestig ati o n al Pr o d uct N u m ber :
P F -0 7 0 8 1 5 3 2
I n vesti g ati o n al Pr o d uct N a me:
N ot A p plica ble ( N/ A )
U nite d S t ates ( U S) In vesti g ati o n al N e w 
D r u g (I N D) N u m ber:
E ur o pe a n Cli nic al Tri al s D at a b ase 
( E u dr a C T) N u m ber:
N/ A
Pr ot oc ol N u m ber:
C 3 9 9 1 0 0 2
P h as e:
1
S h ort Title: A P hase 1 St u d y of M ulti ple Escalati n g Oral D oses of 
P F -0 7 0 8 1 5 3 2 i n A d ult Partici pa nts W it h T y pe 2 Dia betes Mellit u 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 h er wise a gree d t o i n writi n g, by 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 u r p oses.  I n t he e ve nt of an y actual o r 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 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
16 January 2020
Not applicable (N/A)
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a 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..................................................................................................... 9
1. 1. S y n o p sis .................................................................................................................... 9
1. 2. Sc he ma ...................................................................................................................... 9
1. 3. Sc he d ule of Acti vities ( S o A) ................................................................................... 1 0
2. I N T R O D U C TI O N ............................................................................................................... 1 7
2. 1. St u d y  Rati o nale....................................................................................................... 1 7
2. 2. Bac k gr o u n d ............................................................................................................. 1 7
2. 2. 3. N o ncli nical Safet y ...................................................................................... 1 9
2. 2. 4. Cli nical E x perie nce wit h P F -0 7 0 8 1 5 3 2...................................................... 2 0
2. 3. Be nefit/ Ris k Assess me nt ......................................................................................... 2 2
3. O BJ E C TI V E S A N D E N D P OI N T S ..................................................................................... 2 4
4. S T U D Y D E SI G N ................................................................................................................. 2 6
4. 1. O verall Desi g n ......................................................................................................... 2 6
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n..................................................................... 2 7
4. 2. 1. P o p ulat i o n(s)...............................................................................................2 7
4. 2. 2. I P A d mi nistrati o n ........................................................................................ 2 7
4. 2. 3. St u d y  Bli n di n g............................................................................................ 2 8
4. 2. 4. E n d p oi nts .................................................................................................... 2 8
4. 2. 4. 1. Safet y ......................................................................................... 2 8
4. 2. 4. 2. C haracterizati o n of P F -0 7 0 8 1 5 3 2 P har mac o ki netics................ 2 9
4. 3. J ustificati o n f or D ose ..............................................................................................3 0
4. 3. 1. D ose Selecti o n -- Part A .............................................................................3 1
4. 3. 2. D ose Selecti o n -- Part B .............................................................................3 1
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4
4. 3. 3. D ose Selecti o n -- P art C ............................................................................. 3 2
4. 3. 4. D ose Ra n ge a n d Mar gi ns ............................................................................ 3 2
4. 3. 5. D ose Titrati o n ............................................................................................. 3 3
4. 4. E n d of St u d y  Defi niti o n .......................................................................................... 3 5
5. S T U D Y P O P U L A T I ON ...................................................................................................... 3 5
5. 1. I ncl usi o n Criteria ..................................................................................................... 3 5
5. 2. E xcl usi o n Criteria .................................................................................................... 3 6
5. 3. Li fest yle C o nsi derati o ns.......................................................................................... 4 0
5. 3. 1. Meals a n d Dietar y  Restricti o ns................................................................... 4 0
5. 3. 2. Alc o h ol, Caffei ne a n d T o bacc o .................................................................. 4 1
5. 3. 3. Acti vit y ....................................................................................................... 4 2
5. 3. 4. C o ntrace pti o n ..............................................................................................4 2
5. 4. Scree n Fail ures ........................................................................................................ 4 3
6. S T U D Y I N T E R V E N TI O N .................................................................................................. 4 3
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................ 4 3
6. 1. 1. A d mi nistrati o n ............................................................................................ 4 3
6. 2. Pre parati o n/ Ha n dli n g/ St ora ge/ Ac c o u nta bilit y ........................................................ 4 4
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................ 4 6
6. 3. Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g ..................................... 4 6
6. 3. 1. All ocati o n t o I n vesti gati o nal Pr o d uct ......................................................... 4 6
6. 3. 2. Brea k i n g t he Bli n d...................................................................................... 4 7
6. 4. St u d y  Inter ve nti o n C o m plia nce ............................................................................... 4 8
6. 5. C o nc o mita nt T hera p y ..............................................................................................4 8
6. 5. 1. Me dicati o ns f or Gl yce mic C o ntr ol: Parts A a n d C o nl y ............................. 4 8
6. 5. 2. A nti h y perte nsi ve a n d L i pi d-M o dif y i n g A ge nts: Parts A, B, a n d C ........... 4 8
6. 5. 3. Ma na ge me nt of Na usea a n d V o miti n g .......................................................4 8
6. 5. 4. Pr o hi bite d Me dicati o ns ............................................................................... 4 9
6. 5. 5. Resc ue Me dici ne ......................................................................................... 5 1
6. 6. D ose M o dificati o n ................................................................................................... 5 1
6. 6. 1. D ose Escalati o n a n d St o p pi n g R ules ..........................................................5 1
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 5
6. 7. I nter ve nti o n After t he E n d of t he St u d y.................................................................. 5 3
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ........................................................................... 5 3
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................5 3
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y ....................................... 5 5
7. 3. L ost t o F oll o w u p .................................................................................................... 5 6
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S............................................................... 5 6
8. 1. Efficac y  Assess me nts..............................................................................................5 9
8. 2. Safet y Assess me nts .................................................................................................5 9
8. 2. 1. P h y sical E xa mi nati o ns ................................................................................ 5 9
8. 2. 2. Vital Si g ns .................................................................................................. 5 9
8. 2. 3. Electr ocar di o gra ms ..................................................................................... 6 0
8. 2. 4. Cli nical Safet y  La b orat or y Assess me nts .................................................... 6 0
8. 2. 4. 1. Fasti n g Fi n gerstic k Bl o o d Gl uc ose ( v ia Gl uc o meter)............... 6 1
8. 2. 4. 2. H y p o gl yc e mia Re p orti n g .......................................................... 6 2
8. 3. A d verse E ve nts a n d Seri o us A d verse E ve nts .......................................................... 6 3
8. 3. 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....... 6 3
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ............................................... 6 3
8. 3. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F ................... 6 4
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es .......................................................... 6 4
8. 3. 3. F oll o w -u p of A Es a n d S A Es ....................................................................... 6 4
8. 3. 4. Re g ulat or y  Re p orti n g Re q uire me nts f or S A Es........................................... 6 4
8. 3. 5. E x p os ure D uri n g Pre g na nc y  or Breastfee di n g, a n d Occ u pati o nal 
E x p os ure ..........................................................................................................6 5
8. 3. 5. 1. E x p os ure D uri n g Pre g na nc y ...................................................... 6 5
8. 3. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................ 6 5
8. 3. 5. 3. Occ u pati o nal E x p os ure ............................................................. 6 5
8. 3. 6. Me dicati o n Err ors ....................................................................................... 6 5
8. 4. Treat me nt of O ver d ose ............................................................................................ 6 6
8. 5. P har mac o ki netics .................................................................................................... 6 7
8. 5. 1. Plas ma f or A nal ys is of P F-0 7 0 8 1 5 3 2......................................................... 6 7
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 6
8. 5. 3. Uri ne f or A nal ys is of P F- 0 7 0 8 1 5 3 2 ........................................................... 6 8
8. 6. 3. B o d y Wei g ht ...............................................................................................7 0
8. 9. Healt h Ec o n o mics ................................................................................................... 7 2
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 7 2
9. 1. Statistical H y p ot heses ............................................................................................. 7 3
9. 2. Sa m ple Size Deter mi nati o n ..................................................................................... 7 3
9. 3. P o p ulati o ns f or A nal y sis ......................................................................................... 7 3
9. 4. Statistical A nal y ses .................................................................................................7 4
9. 4. 1. Efficac y  A nalys es ....................................................................................... 7 4
9. 4. 2. Safet y A nal ys es .......................................................................................... 7 4
9. 4. 2. 1. Electr ocar di o gra m A nal y s es...................................................... 7 5
9. 4. 3. P har mac o ki netic A nal y ses .......................................................................... 7 5
9. 4. 3. 1. P F -0 7 0 8 1 5 3 2 P har mac o ki netics ................................................ 7 5
9. 5. I nteri m A nal ys es ..................................................................................................... 7 9
9. 5. 1. Data M o nit ori n g C o m mittee .......................................................................7 9
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.......................................................................................................... 8 0
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............... 8 0
1 0. 1 . 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................8 0
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc o l or IC H G C P .........................................................................8 0
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................ 8 1
1 0. 1. 3. Data Pr otecti o n ......................................................................................... 8 2
1 0. 1. 4. Disse mi nati o n of Cli ni cal St u d y Data ...................................................... 8 2
1 0. 1. 5. Data Q ualit y Ass ura nce ............................................................................ 8 4
1 0. 1. 6. S o urce D oc u me nts .................................................................................... 8 5
1 0. 1. 7. St u d y  a n d Site Cl os ure.............................................................................. 8 5
1 0. 1. 8. P u blicati o n P olic y ..................................................................................... 8 6
1 0. 1. 9. S p o ns or’s Q ualifie d Me dical Pers o n nel ................................................... 8 6
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests................................................................. 8 8
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 ...................................................................... 9 0
1 0. 3. 1. Defi niti o n of A E ....................................................................................... 9 0
1 0. 3. 2. Defi niti o n of S A E ..................................................................................... 9 1
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 ....................... 9 2
1 0. 3. 4. Re p orti n g of S A Es .................................................................................... 9 5
1 0. 4. A p pe n di x 4: C o ntrace pti v e G ui da nce a n d C ollecti o n of Pre g na nc y  
I nf or mati o n ................................................................................................................ 9 6
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................... 9 6
1 0. 4. 2. Fe male Par tici pa nt Re pr o d ucti ve I ncl usi o n Criteria................................. 9 6
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ( W O C B P) .......................................... 9 6
1 0. 4. 4. C o ntrace pti o n Met h o ds ............................................................................. 9 7
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-u p Assess me nts ...... 1 0 2
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ................................. 1 0 4
1 0. 8. A p pe n di x 8: A b bre viati o ns ................................................................................. 1 0 6
1 1. R E F E R E N C E S ................................................................................................................ 1 1 1
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 8
LI S T O F T A B L E S
Ta ble 1.
Part A ( 4 -wee k i n T 2 D M): O verall Visit Sc he d ule a n d List of 
Pr oce d ures ( use wit h Ta ble 2 f or f ull detail s)........................................... 1 1
Ta ble 2.
Part A ( 4 -wee k i n T 2 D M): Detaile d Sc he d ule (selecte d st u d y  da ys)....... 1 2
Ta ble 3.
Part B ( 6 -wee k i n O bese): O verall Visit Sc he d ule a n d L ist of 
Pr oce d ures ( use wit h Ta ble 4 f or f ull details) ........................................... 1 3
Ta ble 4.
Part B ( 6 -wee k i n O bese): Detaile d Sc he d ule (selecte d st u d y  d a ys) ........ 1 4
Ta ble 5.
Part C ( 6 - wee k i n T 2 D M): O verall Visit Sche d ule a n d L ist of 
Pr oce d ures ( use wit h Ta ble 6 f or f ull details) ........................................... 1 5
Ta ble 6.
Part C ( 6 -wee k i n T 2 D M): Detaile d Sc he d ule (sel ecte d st u d y da ys) ....... 1 6
 
 
 
Ta ble 9.
Sa m ple Titrati o n Sc he me a n d D osi n g Para di g m f or St u d y  Part A........... 3 4
Ta ble 1 0.
P o p ulati o ns f or A nal y sis ........................................................................... 7 4
Ta ble 1 1.
Defi niti o n of Plas ma P K Para meters f or P F -0 8 7 0 8 1 5 3 2 .......................... 7 6
Ta ble 1 2.
Defi niti o n of Uri ne P K Para meters f or P F -0 8 7 0 8 1 5 3 2 ............................ 7 7
Ta ble 1 4.
Pr ot oc ol -Re q uire d Safet y L a b orat or y Assess me nts .................................8 8
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
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PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 9
1. PROTOCOL SUMMARY
1.1. Synopsis
Not Applicable.
1.2. Schema
This schema is provided for illustrative purposes only. 
TBD: To Be Determined; N: number of participants randomized; FU: follow-up
Dose levels represent PF-07081532 or matching placebo. Dose levels provided here may be adjusted based on 
emerging data and doses for Parts B and C, if conducted, will be determined based on emerging data.
Some cohorts may have titration schedules of less than, or more than, 14 days.
Based on emerging data, some cohorts (of Parts A, B, and/or C) may be run concurrently.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 10
1.3. Schedule of Activities (SoA)
The tables below provide an overview of the protocol visits and procedures that are tailored 
for specific cohorts as follows:
Part A: Table 1 and Table 2
Part B: Table 3 and Table 4
Part C: Table 5 and Table 6
Refer to the STUDY ASSESSMENTS AND PROCEDURES section of the protocol for 
detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA
tables, in order to conduct evaluations or assessments required to protect the well-being of 
the participant.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 1
T a b le 1 .
P art A ( 4- w ee k i n T2 D M) : O v er all Visit Sc h e dul e a nd Lis t of P r oced u r es ( use wit h T a ble 2 f or f ull det a ils)
S cree n
St u d y D a y ( all ac ti vities a t 0H [ pri or t o d osi n g] u n less other w ise s pecifie d) 
F oll o w-u p
E a rl y
- 2 - 1 1
2 3 4 5-
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 2 2 3-
2 4
2 5 2 6-
2 7
2 8 2 9 3 0 3 1
3 5-
4 2
5 6 -
6 3 a
Ter mi n a ti on
O ut patie nt v isit (after ≥8 H fast)
x
x
In f orm e d co nse nt
x
De m o gr ap h y an d h e i ght
x
I n patie nt sta y at C R U
x





















x
Me dica l hist or y 
x
x
R evie w d ru g, alc o h o l, to b acco u se
x
x
x
Re vi e w pri or/c o n co m itan t treatm ent s
x
x
x
x
x
A d verse eve n t mo nit ori n g
x 
x





















x 
x 
x 
x
Re vie w c o n trace pti on us e/re q uire ment
x
x
x
x
x
x
P h ysica l e xa mi nati o n b
x
x
x
x
x
B o d y w ei g ht
x
x
x
x
x
x
x
x
Bli n de d IP ad mi nistr ati on c
x
x x x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
S u pi ne 1 2 -lead E C G d
x
See Ta ble 2
See Ta ble 2
x e
x
x
x
S ee Ta ble 2
x e
x
See Ta ble 2
x e
x
See Ta ble 2
x
x
x
x
x
S u pi ne vital si g ns (bl o o d press ure an d p u lse rate) f
x
x e
x
x
x
x e
x
x e
x
x
x
x
x
x
F asti n g fi n gerstic k bl o o d gl u c o se m easu re m e nt g
x
x x x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Sta n dar d ized meals/ sn ac ks h
x
x x x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Bl o o d S a m pli n g f or:
S afet y lab o rato ry testsi
x
x
x
x
x
x
x
F S H j, HI V, He p Bs A g, He p B c A b , H C V A b
x
P F -0 7 0 8 1 5 3 2 P K
x e
x
x
x e
x
x e
x e, k x k
x k
x
U ri ne Sa m pli n g f or:
U ri ne dr u g test
x
x
Ur i nal ysis (an d m icro sc o p y, as ap pr o pri ate)
x
x
x
x
x
x
x
a.
T h is f oll o w-u p c o nt act ma y be c o n d ucte d as a p h o ne-call. 
b.
F ull p h ys ical e x a m at ti mes i n dicate d; li mite d e xa m f or previ o u s fin di n gs , ne w/ o p e n A E s, or i n vestigat o r di scretio n.
c.
D ose a d mi nistratio n t o occ ur wit h bre a kfast or mi xe d meal d a ily fr o m  D ay 1 t o Da y 2 8, i n clusi ve; see Sect i o n 5. 3 a n d Secti o n 6 .
d.
Si n gle 1 2 -lead E C G at Scree ni n g, fol lo w -u p a nd Earl y T er mi n ati o n (if a p plicab le). Meas u re i n tri plicate at all oth er tim es i n dicate d.
e.
Me as ure me nt/sa m ple at 0 H c orres p o n ds t o t he 2 4 H ti mep oi nt as detaile d i n Ta ble 2 (ie, liste d i n b ot h ta bles, b ut o nl y o ne sa m ple / meas ure me nt s h o ul d be c ollected).
f.
Si n gle vit a l si g ns at Scree ni n g, foll o w- u p a n d Earl y T er mi nati o n (if ap plica bl e).
Meas u re i n tri plicate at all ot her ti mes i n dicated.
g.
F i n gerstic k gl uc ose via g l uc o met er o n a d missi o n t o C R U an d pr i or to br ea kfast o n all i n patient d a ys ; ma y be m ore fre q ue nt at t h e dis creti o n of t he i n vesti gator.
h.
Me a ls t o be pr o vi de d at a p pr o xi mat el y 0 H, 4 H, a n d 1 0 H relati ve to d osi n g ; s nac ks t o be pr o v i de d.
Refer to Secti o n 5. 3 .
i.
See A p pe n di x 2 f or s afet y l a b tests t o be c ollected at eac h ti me p oi nt a n d Se cti o n 5. 3 f or fasti n g re q ui reme n ts.
j.
F S H i n fema les t o c o nfir m p ost men o p a u sal stat us o nly.
k.
P K sa m ples o n D a ys 2 9, 3 0 a n d 3 1 t o be c o llecte d 2 4 H , 3 6 H , 4 8 H , a n d 7 2 H after the fi nal d ose o n Da y 2 8.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 2
T a ble 2 . 
P art A ( 4- w ee k i n T 2D M ): Det a ile d Sc he d ule (select e d st u d y d a ys)
St u d y D a y
H o urs Re l ativ e t o D osin g at 0 H a
0
0. 2 5 0. 5
1 
1. 5 
2 
3 
4 
6 
8
1 0
1 2
1 6
2 4 b
T ri plicate, su p in e 1 2 -lead E C G
Da y s -1 , 1 , an d 2 8 . p l us D ay 1 4 or D a y 2 1 k
x
x
x
x
x
x
x
T ri plicate, su pi n e vital si g ns ( blo o d p ress ure a n d p ul se)
Da y s -1 , 1 , a n d 2 8 p lus D ay 1 4 or Da y 2 1 k
x
x
x
x
x
x
x
F asti n g fi n ge rstic k bl o o d glu c ose m easure m e n tb, c
A ll i npat ie nt d ays
x
Sta n d ard ized meal/ sn ac k d
A ll i n patie nt da ys
x e
x
x
x
Bli n de d in v estiga tio n al pro d u ct a d mini stratio n
Dai ly: D a y 1 t o Da y 2 8
x f
B l o o d s a mpl in g f or :
- Saf et y lab o rat or y testsg
Da y s -1 , 1 4 , 2 1 , a nd 2 8
x h
- H b A 1 c, T S H
D a ys -1 a n d 2 8
x
-
- P F -0 7 0 8 1 5 3 2 P K
D a y s 1 a n d 2 8 pl us D a y 1 4 or D a y 2 1 k
x
x
x
x
x
x
x
x
x
x
x
U ri ne s am pli n g f or:
- U rina ly sis a n d m icr osco p y , as a p p ro pr iate
Da y s -1, 1 4 , 2 1 , an d 2 8
x
- P K p red ose s p o t uri n e ( urin e bla n k )
D a y 1 o n l y
x
- P F -0 7 0 8 1 5 3 2 P K m
Da y 2 8 o nl y
x
 
 
 
 
 
 

x
 

x

x
a.
Da y - 1, time of 0 H pr o ce d ures t o ma tch a p pro xi mate pl a n ne d cl o c k ti me of c o llecti on o n Da y 1. All o th e r days , 0 H pr oce d u res co m p lete d pre-d o se.
b.
T he 2 4 H sam ple / meas ure me n t is to b e c o llecte d pri or t o d osi n g o n t he f oll o wi n g m o r ni n g, as i n dicated i n Ta b le 1 .
c.
O btai n fasti n g fi ng erstic k b l o od g luc ose mea s ure me nt via gl u c o meter b ef ore bre a kfast o n all d a ys w hi le i n p atie nt.
d.
Sta n d ar dize d meals/s n ac ks to b e p ro vi d e d o n al l d a y s w hil e i n patie n t;
f.
D osi n g t o o cc ur w ith br eakfast
d ail y fr o m Da y 1 t o Da y 2 8 , incl u si ve.
g.
S ee A p p e n d i x 2 : Cli ni cal La b orat or y Te sts f or safety la b tests t o be c ollecte d at eac h ti me p oi nt.
h.
See Secti o n 5. 3 f or fasti n g re quire me nts .
k.
D ecisio n t o c o n d uct t he i n dicate d p r oce d ures o n Da y 1 4 or Da y 2 1 will be pr o vi de d i n wr iti ng pri o r t o init iatio n of d o si n g f or each c o h ort.
m.
Uri ne c o llecti on f or P F- 0 7 0 8 1 5 3 2 P K t o occ ur o v er 0- 6 H, 6 -1 2 H , an d 1 2- 2 4 H .  Partic i pa nts s h o ul d v oi d a n d discar d t he sa m ple pr i or t o t he first sa m pli n g i nter val a n d v oi d at 
t he e n d of eac h sa m pl i n g i nter val f or i ncl usio n i n t he v ol u me c ollecte d o ver t hat i nter val.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 3
T a ble 3.
P art B ( 6 -wee k i n O bes e): O ve r all Visit Sc he d ule a nd Lis t of Pr o ce dur es ( use wit h T a ble 4 f or f ull details )
Pr ot oc o l Activit y
Scr ee n
St u d y D a y (all act i vities at 0 H [ pri or t o d os i ng] u nl ess ot he r w ise s pe cifie d) 
F oll o w- u p
E arl y
- 3a - 2 - 1
1 2 3- 7 8 9- 1 3 1 4 1 5- 2 1 2 2 2 3- 2 7 2 8 2 9 3 0 -3 5 3 6
3 7 - 4 0 4 1
42 4 3 4 4 4 5 4 9- 5 6 7 0 -7 7 b Ter m
O ut pa tie nt vi sit (after ≥8 H fast)
x
x
Inf or m e d co n sen t
x
De m o gr ap h y  an d h e i g ht
x
I n patie nt stay at C R U a
x






 
 
 
 

 
 

 




x
Me di cal his to ry 
x
x
R e vie w d ru g , alc o h o l, t obac c o use
x
x
x
R ev ie w prior /c o nc o mi tant tr eat me nts
x
x
x
x
x
A d verse e ve nt mo nit or i n g
x 
x






 
 
 
 

 
 

 




x 
x 
x 
x
R e vie w co n tracep tio n u se/re q uire me n t
x
x
x
x
x
x
P h ysic al e xa mi na ti o nc
x
x
x
x
x
B o d y w ei g ht
x
x
x
x
x
x
x
x
x
x
Bl in de d I P a d mi n istrati o nd
x x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
S u pi ne 1 2 -lea d E C G e
x
See Ta ble 4
See Ta ble 4
S ee T able 4
x f
x
x
x
See Ta ble 4
x f
x
See Ta ble 4
See Ta ble 4
x f x
x
x
x
S u p ine v ital si gns ( bl o od pres s ure an d p u lse)g
x
x f
x
x
x
x f
x
x f x
x
x
x
F asti ng fi n gerstic k bl o o d gl u c o seh
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
S ta n dardize d mea ls/sn ac ks i
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
B l o o d S a m p lin g f or:
- S afet y la bo rato r y testsj
x
x
x
x
x
x
x
- F S H ,k
H IV , H ep B sA g, H e p Bc A b , H C V A b , H b A 1c
x
- P F -0 7 0 8 1 5 3 2 P K
x f
x
x
x
x f
x
x f,l x l x l
x
Uri ne S a m pl i ng f or:
- U ri ne d r u g test
x
x
- U ri nal ysis (an d mi cro sco p y , as a p p ro p riate)
x
x
x
x
x
x
x
b.
T his f oll o w -u p c o ntact ma y be c o n d ucte d a s a p h o ne call
c.
F ull p h ys ical e x a m at ti mes i n dicated; li mite d e xa m f or previ o u s fin di n gs, ne w/ o p e n A Es, or i n vestigat o r di scretio n.
d.
D ose a d mi nistratio n t o occ ur wit h brea kf ast dail y fr om Da y 1 t o Da y 4 2 , incl u sive ; see T able 4 , Secti o n 5. 3 a n d Secti o n 6 .
e.
S i n gle 1 2-le a d E C G at Screeni n g, f oll o w- u p a nd Ea rl y Te r minati o n (if a p plica ble). Meas u re i n tri plicate at all ot her ti mes in d icated.
f.
Me as ure me nt/sa m ple at 0 H c orres p o n ds t o t he 2 4 H ti mep oi nt as detaile d i n Ta ble 4 (ie, liste d i n b ot h ta bles, b ut o nl y o ne sa m ple/ meas ure me nt s h o ul d be c ollecte d ).
g.
Si n gl e vi t al si g ns at Scree ni n g, foll o w -u p a n d Earl y T er mi n ati o n (if a p p lica ble). Me as ure i n tri plicate at all ot her time s i n dicate d.
h.
F i n gerstic k gl uc os e via g l uc o m et er o n a d m issi o n t o C R U a n d pr i or to br ea kfast on all i n patie nt da ys; ma y b e m o re freq ue n t at t he discreti o n of t he i n ves ti gato r.
i.
M e als t o be pr o vi d e d at a p pr o xi mately 0 H, 4 H, a nd 1 0 H relati ve t o d osi n g ; s nac ks ma y b e pr o vi de d .  Refer t o Sect i o n 5. 3 .
j.
See A p pe n d i x 2 f or s afety l a b tests t o be c ollecte d at eac h ti mep oi nt, s ee Secti o n 5. 3 f or fastin g re q uir e ments .
k.
F S H in fema les t o co nf ir m p o st me n opa u sal stat us o n ly.
l.
P K sa m ples o n Da y 4 3 , 4 4, an d 4 5 are to b e c olle cte d 2 4 H , 3 6 H , 4 8 H , a n d 7 2 H after t he fi nal P F- 0 7 0 8 1 5 3 2 d os e o n Da y 4 2.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 4
T a ble 4 .
P a rt B ( 6 - w ee k i n O bes e): Det aile d Sc he d ul e (selecte d st u d y d a ys)
St u d y D a y
H o ur s Rel at i ve t o D o sin g a t 0 Ha
0
0. 2 5 
0 . 5
1
1. 5
2 
3 
4 
6 
8
1 0 
1 2 
1 6 
2 4 b
T ri plicate, su pi n e 1 2 -lea d E C G 
D a y s -1, 1, 2 8 , a n d 4 2
x
x
x
x
x
x
x
Tri p licate, su pi n e vi tal sig n (bl o o d p ress ure a n d p u lse rate)
Da y s -1, 1, 2 8 , a n d 4 2
x
x
x
x
x
x
x
F astin g fi n ger stic k bl o o d gl u c ose mea s ure ment c
A ll in p a tie nt d a ys
x
St an d ar dized mea l/s nac k d
A ll i n patie nt da ys
x
x
x
x
B lin d e d in v estiga tio nal pr o d u ct ad m inistr atio n
D ail y: Da y 1 t o 4 2
x e
Bl o o d s a m p li ng f or:
- S afety lab o rat or y testsg
Da y s -1 , 2 8, an d 4 2
x h
- P F-0 7 0 8 1 5 3 2 P K
Da ys 1 , 2 8 , a n d 4 2
D a y 4 1 0 H o n l yf, k
x
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
-
Ur i ne s a mp li ng f or:
- Ur i nal ysis a n d m icrosc o p y , as a p p r o priate
Da y s -1 , 2 8 , a n d 42
x
a.
D a y -2 a n d Da y -1, ti me o f 0H pr oc e d ures t o matc h a p pr o xi ma te pla n ne d clo c k t i me of c ollecti o n o n Da y 1.
Al l ot her da ys, 0 H pr oc ed u res c o mpl ete d pre-d os e.
b.
T he 2 4 H sa mp le is to be c ollect e d pri or t o d o sin g o n t h e foll o wi n g m or ni n g, as i n dicated i n Ta ble 3 .
c.
F i n gerstick gl uc ose via g l uc o met er o n a d missi o n t o C R U a nd pr i or to br ea kfast o n all i n patie nt d a ys; ma y be m o re freq ue nt at t h e discreti o n of t he i n ves tigat or.
d.
St a n dar di zed m eals/s nacks t o b e p r o vi de d on all da y s whi le i np a tie nt.
Refer t o Secti o n 5. 3 .
e.
D o si n g t o o c c u r wi t h bre a kfast dail y fr o m Da y 1 t o D a y 4 2, i ncl usi ve.
g.
S ee A p pe n d i x 2: Cli ni cal La b orat or y T ests f or safet y la b tests t o be c ollected at eac h ti mep o i nt.
h.
S ee Se ctio n 5. 3 f or fasti ng r e q uir e ments .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 5
T a ble 5.
P art C ( 6- w ee k in T 2 D M ): O v er all Visit Sc he d ule a n d List o f Pr oce d ures ( use wit h T a ble 6 for f ull det a ils)
P r otoc ol Ac tivit y
S cree n 
St u d y D a y ( all ac ti vities at 0H [ pri or t o d osi n g] u nl ess ot her w ise s pecifie d)
F ol l o w U p 
E arl y
- 2 - 1
1 
2
3- 7
8
9- 1 3 1 4 1 5- 2 1 2 2 2 3- 2 7 2 8 2 9 3 0- 3 5 3 6
3 7 - 4 1
4 2
4 3 
4 4
4 5
4 9- 5 6 7 0 - 7 7a Te r mi n ati o n
O u tpa tie n t v isit (after ≥8 -H fast)
x
x
In f or med co n se nt
x
De m o g rap h y a n d h ei g ht
x
I n patien t sta y at C R U







 
 
 
 

 
 

 

 

x
M edical hist or y 
x
x
Re v ie w d ru g , alco h o l, to b a cc o us e
x
x
x
Re vie w p ri or/c o nc o mi ta nt treat me n ts
x
x
x
x
x
A d ve rse eve nt m o nit ori n g
x







 
 
 
 

 
 

 

 

x 
x 
x 
x
Re vie w c o nt race pti o n u se/re q uire me nt
x
x
x
x
x
P h y sical e xa m in a ti on b
x
x
x
x
x
B o d y w ei ght
x
x
x
x
x
x
x
x
x
x
B lin d ed I P ad m i nistratio n c
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
S u pi n e 12 -lea d E C G d
x
See  Ta ble 6
See  Ta ble 6
x e
x
x
x
See  Ta ble 6
x e
x
See  Ta ble 6
x e
x
x
x
x
S u pi ne vital si g ns ( bl o o d press ure an d p ul se)f
x
x e
x
x
x
x e
x
x e
x
x
x
x
F asti ng fi n gers tick bl o o d gl u cose meas ur e me nt g
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
S tan dar dize d meals/ s nac ks h
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
B l o o d Sa m p li n g for :
- Saf et y la b orat or y testsi
x
x
x
x
x
x
x
- F S H ,j HI V , He p B s A g, He p Bc A b, H C V A b
x
- P F - 0 7 0 81 5 3 2 P K
x e
x 
x 
x 
x e
x
x k
x k
x k
x
Uri n e S a m p li ng f or:
- U rin e dr u g test
x
x
- Uri n alysis (an d mic r osco p y , as a p pr o p riate)
x
x
x
x
x
x
x
a.
T his f oll o w -u p c o ntact ma y be c o n d ucte d as a p h o ne call
b.
F ull p h ysic al e x a m at ti mes i n dicate d ; li mite d e xa m f or pre vi ou s fi n di n gs, ne w/ o pe n A Es, or i n vesti gat or discreti on.
c.
D ose a d mi nistratio n t o occ ur wit h brea k fast
d a il y o n Da ys 1 t o 4 2 , in c l usi ve, see S ecti o n 5. 3 an d Secti o n 6 .
d.
S i ngle 1 2 -lea d E C G at Screeni n g , fol l o w-u p a nd Ea rly Ter m i natio n (if a p pl icable) . Meas ure i n tri plicate at all o ther time s i n dicated.
e.
Me as ure me nt/sa m ple at 0 H c orres p o n ds t o t he 2 4 H ti mep oi nt as detaile d i n T a ble 6 (ie, liste d i n b ot h ta bles , b ut o nl y o ne sa m ple/ meas ure me nt s h o ul d be c ollecte d).
f.
Si n gle vit al si g ns at Sc ree nin g, f oll ow- u p an d E arl y T er mi nati o n (if a p plica b le). Me as ure in trip licate at all ot her times i ndicate d.
g.
F i n gerstic k gl uc ose via g l uc o met er o n a d missi o n t o C R U a n d pr i or to br ea kfast o n all i n patie nt d a ys; ma y b e m ore fre q ue n t at t he discreti o n of t he i n ve sti gato r..
h.
M e als t o be pr o vi d e d at a p pr o x i mately 0 H, 4 H, a n d 1 0 H relative t o d os i ng; s nac ks m a y be pr o v ide d . Refer t o Secti o n 5. 3 .
i.
See A p pe n d i x 2 f or safe t y la b tests t o b e c ollecte d at eac h ti me p oi nt , see Secti o n 5. 3 for fasti n g r e q uir e me nts.
j.
F S H i n fe males t o co nfir m p o st me n o pa usal status o nl y. 
k.
P K s a mpl es o n D a y 4 3, 4 4 , a nd 4 5 are t o b e col lecte d 2 4 H, 3 6 H , 48 H , a nd 7 2 H aft er t h e fi nal P F -0 7 0 8 1 5 3 2 d o se o n Da y 4 2.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 6
T a ble 6.
P ar t C ( 6-wee k i n T 2 D M) : D e t aile d Sc hed ule ( selecte d st ud y d a ys )
St u d y D a y
H o urs Rel ati v e to D os i n g at 0 Ha
0
0. 2 5
0. 5 
1 
1. 5 
2 
3 
4 
6 
8
1 0
1 2
1 6
2 4 b
Tri p licate, s up i ne 1 2 -lea d E C G
D a ys -1, 1, 2 8 , an d 4 2
x
x
x
x
x
x
x
T rip licate, su pi n e vital si g n (bl o o d p ress ure an d p u lse)
D a ys -1 , 1, 2 8 , a n d 4 2
x
x
x
x
x
x
x
F astin g fi ng erstic k bl o od gl u cose me asure me nt b, c
A ll i n patien t d a ys
x
Sta n dar d ized me al/s nac k d
all in p atient d a ys
x e
x
x
x
B li n de d in v esti gatio n al p r o du ct a d mi nist rati o n
Dail y: Da y 1 t o D a y 4 2
x f
B l o o d sam pl in g fo r:
- S afet y lab orat o r y testsg
D a ys -1 , 2 8 , a n d 4 2
x h
- H b A 1c, T S H
Da y s -1 , 2 8 , a n d 4 2
x
- P F -0 7 0 8 1 5 3 2 P K
Da y s 1, 2 8 , a n d 4 2
x
x
x
x
x
x
x
x
x
x
x
- U rine sa m pli n g f or:
- Uri n alysis an d m icr osco p y , as a p p ro p riate
Da ys -1 , 2 8 , a n d 4 2
x
- P K pr e d ose s po t ur i ne ( urin e bla n k )
Da y 1 o nl y
x
- P F-0 7 0 8 1 5 3 2 P K
Da y 4 2 o n l yk
x
 
 
 
 
 
 

x
 

x

x
a.
O n D a y -1, ti me of  0H pr o ce d u res t o matc h ap p r oxi m ate pla n n e d cl o c k ti me of c ollecti o n o n D a y 1. Al l ot her da y s, 0 H pr oc e d u res t o be c o m p leted pr e- d ose.
b.
T he 2 4 H sam ple is to be c o llecte d pr ior t o d o si n g o n t he f oll o wi n g m or ni n g , as in dicate d i n T a ble 5 .
c.
F i n gerstic k gl uc ose via g l uc o met er o n a d missi o n t o C R U a n d pr i or to br ea kfast o n all i n pati e nt d a ys; ma y b e m or e freq u e nt at t h e discreti o n o f the i n ves ti gator.
d.
St a n dar dized m eals/sn a c ks t o b e pr o v i de d o n a ll d a ys w hi le i np atie n t;
f.
D o sin g t o o cc ur w ith bre a kfast 
d aily fro m Da y 1 t o d a y 4 2 , i ncl u si ve.
g.
See A p pe n di x 2 : Cli ni cal La b orat or y Te sts f or safet y la b tests to be c ollecte d at eac h ti me p oi nt.
h.
S ee Secti o n 5. 3 f or fasti n g req uire me nts.
k.
Ur i ne coll ecti o n f or P F -0 7 0 8 1 5 3 2 P K to occ u r o ver 0-6 H , 6- 1 2 H, an d 1 2- 2 4 H . Partici pant s sh o ul d v oi d a n d discar d t he sa m ple pri or t o t he first sa m pl i n g i nter val a n d v oi d at
t he e n d of eac h sa m pl i n g i nter val f or i ncl usi o n i n t he v ol u me c ollecte d o ve r t hat i nter val. 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 7
2. I N T R O D U C TI O N
Gl u ca g o n -li ke pe pt i de-1 ( G L P- 1) is a neu r oen d oc ri ne h o r m one t hat is pre d omi n a ntly
release d fr o m t he sm all i ntestine i n resp o ns e to f o o d i n take .1  Activati o n of t he G L P- 1
recep t or ( GL P -1 R) stim u lates i ns uli n release, i nh i bits gl uca g o n secreti on i n a gl u c o se-
de pe n de nt ma n ner , a nd d ela ys ga stric e mpt yi n g .2 ,3 I n a d diti on, G L P- 1 h a s been s h o w n t o 
incr ease satiet y a nd s u p press f o o d inta ke. 4
P F- 0 7 0 8 1 5 3 2 is a p ote nt an d se lecti ve, orall y a d mi nistered , sma ll m olecul e G LP -1 R a g o nist
that is b ei n g de vel o pe d as a n adj u nct t o die t a nd e x er cise t o i mpr o v e gl y ce mi c c o ntr ol i n 
a d ults wit h t yp e 2 dia bet es melli t us (T 2 D M).
2. 1. St u d y R a ti o nale
T he p ur p ose of t his st ud y  is t o e valuate t h e safet y, tol era bilit y , a n d p h a r mac oki netic s (P K ) of 
m ult i ple o ral do ses of P F-0 7 0 8 1 5 3 2 i n par tici pan ts w it h in a deq uat el y co ntr o lled T 2 D M o n
m etf ormi n an d o pti o na ll y i n n o n- dia b etic o bese part icipa nts.
2. 2. B a c kgr o u n d
Di abete s is esti mate d t o affect a ppr o xi mate l y 4 2 5 m illi o n a dult s ( 8. 8 % of pe o pl e a ge d 
2 0- 7 9 ye ars) w orl d- wi de. 5 ,6 T h e i ncrease i n t he gl o bal pre val e nce of T 2 D M is lar gel y 
attri but e d to ri si n g rates of e xcess bo d y wei g h t an d o besit y. 7
T 2 D M is c h aracteriz e d b y i nsuli n res ista nce, a dis order in w h ich cells d o n ot re s po n d 
effe cti vely t o i ns uli n, resulti n g i n hig he r bl o o d g l uc ose le vels. Ele v ate d b lo o d gl uc o se le vels
a n d incr easi n g se verit y of ins uli n resista nce res ult in t he ne e d f or more i ns uli n o ve r time ,
eve n t uall y resul ti n g in p ro gr essi ve pa n c reatic -cell fail ure.8 P atie nts wi t h p o orl y c o ntr ol le d
T 2 D M ha v e an i ncrease d ris k of de velo pi n g co m p licati o ns asso ciated wi t h b ot h 
m icr ova scul ar a nd macr o v asc ular d isease, i ncl udi n g ne p hr o pat h y, n e u r o path y , reti no pat h y, 
cardi o vas c ular dis ease a n d str o ke, a n d are at 2 t o 4 time s i ncrease d ris k of m or tality t ha n
a d ults w h o d o n o t ha ve dia b etes.9 W hi le exis ti ng p ha r mac olo gica l o ptio ns f or the treat ment
o f diab etes may pr o vi d e satisfact or y gl yce mic co n trol f or s ome pa tie nts, t here re mai n man y  
p atients w h o d o n o t achie v e tar get gl yc ate d he m o gl o bi n ( H b A1c) le vels, s ug ge sti ng a n eed
f or ad diti o na l ther a peu tic o pt i on s. 
Bas e d o n t h e cli nical hist or y of i njec ta ble G L P- 1 R a go nist s, an oral G L P -1 R ag o nist is
ex p ected t o i m pr ove gl u c ose co ntr ol a n d red uc e H b A 1c l e vels in pati e nts wit h T 2D M, w hil e 
de cre asi n g f o o d i nta ke a n d bo d y w eig h t a n d a voi di n g t he s ub c uta n eo us i njecti o n re q uired b y 
the ma jori ty of c urre ntly a vai la ble pe pt i dic GL P- 1 R a go n ists.  
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 9
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. 2. 3. N o n cli nic al S afet y
P F- 0 7 0 8 1 5 3 2 wa s e v al uate d i n g e netic t oxic ity st u dies a n d oral, re peat- d ose rat an d
cy n o m ol g us m o n k e y to xi cit y st ud ies as well as car di o vascular a n d ne u r o pu l m o nary s afet y
p h ar macol o g y stu dies .
T he cy n o m ol g us m o n ke y i s t he onl y  p har mac ol ogi cally rel e va nt 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 0
n o ncli n ical s pecies (P F -0 7 0 8 1 5 3 2 a ctiv ates t he G L P- 1 rece pt or), t heref ore rat was use d t o
c haract erize o ff-tar get activit y o f t he m o lecule .
I n t he 8-we e k oral ga va ge t oxi cit y st ud y c on d u cte d i n cy n o m ol g u s m o n ke y at 2 0, 6 0, a n d 
1 0 0 m g/ k g/ da y, n o a d verse effec ts we re detected.
 
A 6- we e k or al ga v a ge to xi city st ud y wa s c on d u ct ed i n W istar Ha n rats at P F- 0 7 0 8 1 5 3 2 d oses
of 3 0, 1 0 0, a n d 3 0 0 m g/ k g / day.   
 
 
 
 
 
T he N O A E L i n t he pi vo t al 8- wee k t o xicit y st u dy i n m o n ke y s w as 1 0 0 m g/ k g/ da y  
 
 an d t h e N O A E L in t he p i v otal 6-wee k t o xic it y stu d y i n rats was 1 0 0 m g/ k g /d a y
P F -0 7 0 8 1 5 3 2 was n ot m ut a gen ic or c l ast o ge nic i n i n vitr o st u dies an d was ne gati v e i n a n i n
vi v o r at micr on ucl e us stu d y . Ba se d on t he m ol ar e x tincti o n c oefficie nt f or P F- 0 7 0 8 1 5 3 2, t he 
p h ot ot o xi c ris k w as e val uate d i n the 3 T 3 N e utral Re d assa y des cri be d i n I nternat i o nal 
C o u ncil f or Harm o nis ati o n ( I CH) S 1 0 a n d w as fo u n d t o be ne g ative f o r p h ot ot o x ic pote ntial .
S afet y ph a rma c olo g y  st u dies t hat we re c o n ducte d t o as sess p otenti al p ha r mac od y na mic
effe cts o n centr al ner v o us a n d res pirat or y s yst em s di d n ot i den tif y a n y effects at d os es u p t o
3 0 0 m g/ k g i n rats.
 
 
F u rthe r details of t he n o n cli nical safety pr o gra m are pr ovi de d i n t he c urre nt IB .
2. 2. 4. C li nic al Ex pe rienc e w ith P F - 0 7 0 8 1 5 3 2
P F - 0 7 0 8 1 53 2 is c urre ntl y b ei n g e val uate d i n a n o n g oi n g P h ase 1 si n gle asce n di n g d ose 
First -i n-H u ma n st u d y, C 3 9 9 1 0 0 1.  C 3 9 9 1 0 0 1 is a n i n vesti gat or - a n d partici pa nt - bli n de d, 
s p o ns or-o pe n, r a n d o mize d, si n gle-asce n di n g oral d ose, 4 -peri o d cr oss o ver, place b o 
s u bstit uti on desi g n i n 2 i nt erlea vi n g c o h orts of healt h y  a d ult partici pa nts.  T he f oll o wi n g is a 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 1
bli n de d i nteri m draf t s u m mar y of t he e mer gi n g cli nical safety a n d P K data a vaila ble t o date
( 7t h Ja nuar y  2 0 2 0). All data pr o vi de d bel o w s h o ul d be c o nsi dere d preli mi nar y  a n d s u bject t o 
u p dat e o n fi nal re p orti n g of t his stu d y ’s res ults.
Si xtee n ( 1 6) partici pa nts ha ve bee n ra n d o mise d t o partici pate i n C 3 9 9 1 0 0 1.  Preli mi nar y ,
draft data fr o m t he fir st 3 d oses i n t h is st u d y are c urre ntly a vaila ble a n d descri be d bel o w. At 
eac h of t he 3 d ose le vel s f or whic h data are c urre ntl y availa ble , 6 partici pa nts recei ve d 
P F - 0 7 0 8 1 5 3 2 a n d 2 part ici pa nts recei ve d place b o.  P F -0 7 0 8 1 5 3 2 or matc hi n g p lace b o was 
orall y a d mini stere d as a s ol uti o n f or m ulati o n i n t he faste d state.  
O ver t he d ose ra n ge of 1 0 m g t o 1 0 0 m g , there ha ve bee n n o cli ni call y si g nifica nt a d verse 
tre n ds o bser ve d i n a ny safet y para meter, i n cl u di n g la b ora t ory test, vit al si g ns a n d E C G. 
T here ha ve be e n n o deat h s, n o s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs), 
a n d n o a d verse e ve nts ( A Es) of se vere i nte nsit y  re p orte d.  T he m ost fre q ue ntl y  re p orte d A Es 
ha ve bee n i n t he gastr oi ntest i nal s yste m, c o nsiste nt wit h mar kete d G L P 1-R a g o nists.
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 2
 
 
 
 
 
 
 
2. 3. Be ne fit/R isk Assess m e nt
T h is stu d y is de si g ne d p ri maril y t o ge nerate safet y, to lera bilit y, a n d P K d at a fr o m a d ult 
par tici pan ts wit h T 2 D M a nd, p ot e ntially , o b ese partici pants w it h o ut T2 D M . T he p ur p ose of 
t he st ud y is t o pr o vi de t he ba sis f or furt h er cli nical de vel op m e nt o f P F- 0 7 0 8 1 5 3 2 as a 
p ot e ntial ne w, p har ma c ol o gical a ge nt f or the treat me nt of T 2 D M .  
B ase d o n t h e cli nical hist or y  of inj ecta ble G LP- 1 R a g o nist s, a n or al G L P - 1R a g o nis t is 
e x pecte d t o i m pr o ve gl uc ose c o ntr ol, red uc e Hb A 1c le vels, di mi nis h f o o d i nta ke, a n d 
d ecrease b o d y wei g ht in patie nts wit h T 2 D M , w hile av oi di n g t he re q uire me nt f or 
s u bc utane o us i njectio n s t hat acc o m pan y t he maj orit y  of c u rre ntly a vai la ble pe ptidic G L P- 1 R 
a g o nists.
A s of t he iss ua nce o f t his pr o t oco l, no s pecific h u ma n r is ks associate d wit h P F - 0 7 0 8 1 5 3 2
a d mi nist rati o n ha ve b ee n ide nt ifie d; da ta g at hered d uri n g n o n cli nical st udi es w it h
P F- 0 7 0 8 1 5 3 2 ar e s um ma rize d in Secti o n 2. 2. 3, a n d preli minar y data e mer gi n g fr o m t he 
o n g oi n g FI H st u d y are gi ve n i n Secti o n 2. 2. 4 . T h e clini cal im pa ct of a n y p o te ntial ris ks wi ll
be mi n i mize d thr o u g h c a utio u s d ose-escalati on , t hat is, hi g her d os es o f P F-0 7 0 8 1 5 3 2 will b e 
a d mi nistered o n l y after l owe r doses h a ve b een f ou n d t o be well t olera ted wit h a n acce ptable
safet y pr ofi le (see Secti o n 4. 2 f or stu d y d esig n r atio nal e, Secti o n 4. 3 for j ustificati on of t he
selecte d d ose le vels, a n d Se cti o n 6. 6. 1 for d os e escalatio n a n d s t op pi n g rul es). I n a dditi o n,
th is st u d y i nclu de s sta ndar d, i nte nsi ve, i n patient m o n it ori ng of t he pa rticip a nts foll o w i ng 
a dm i nistrati o n o f m ulti ple, oral d oses o f t h e i n vesti gati o nal pr o d uc t (I P). Cli nic al safet y
la bora t or y tests, th or o u g h assess me nt s of v ital si g ns a n d electr ocardi o gra ms ( E C G s), p h ysical 
e xami nati o ns a n d a dv erse e ve nt ( AE ) m o nit ori ng w ill pr o vi de esse ntial data t o e valuat e the
safet y a nd t olera bil it y of P F- 0 7 0 8 1 5 3 2.
T he p ot e ntiall y i mp or ta nt ris ks of mar kete d i njecta ble G LP- 1 R a g o nis ts, base d o n t he
ap pr o ve d la b eli n g ( Unite d Stat es Pac ka ge I nsert a n d E ur o p ean U n i on ( E U ) S u m mar y of 
Pr o d uct C h aracteristics) are s u m marize d i n t he c urre nt P F -0 7 0 8 1 5 3 2 I B.  Alt h o u g h t here is 
n o e vi de n ce to d ate t o s ug ge st t hat P F- 0 7 0 8 1 5 3 2 w o ul d cause a h y pe rse nsitivi t y reacti o n, as 
a preca uti on, parti ci pa nts wit h a hi st or y of a k n o w n h y p erse nsiti vit y reacti o n t o a n y G L P- 1 R 
ag o ni st s h o ul d n ot be e nr olle d i n st u dies wi t h P F-0 7 0 8 1 5 3 2 , see Secti o n 5 .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 23
More detailed information about the known and expected benefits and risks and reasonably
expected adverse events of PF-07081532 may be found in the IB, which is the SRSD for this 
study.
Considering all available clinical and nonclinical data, the benefit-risk profile of
PF-07081532 supports continued clinical development.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 4
3. O B J E C TI V E S A N D E N D P OI N T S
Pr i m ar y O b jecti ve:
Pri m a r y E n d p oi nts : 

T o e val uate t he safet y a n d t olera bilit y of 
escalati ng, m ulti ple d oses o f 
P F- 0 7 0 8 1 5 3 2, orall y ad mi nis tered t o a d ult
p artici pa nts wit h T 2 D M i na de q uately 
c o ntrolle d b y  metf ormi n an d , if co n d uct e d,
t o n o n- dia betic o be se p a rtici pa nts.

Asses sme n t of A E s, safet y la bora t or y 
tests, vital si g ns a n d 1 2-lea d E C Gs .
Se c on d ar y O b jecti ves:
Sec o n d ar y E n d p o i nts: 

T o c haracterize plas m a P K of 
P F - 0 7 0 8 1 5 3 2 foll o wi n g m ulti p le d oses 
a d mi nistere d orally to a d ult p articipa nt s
w ith T 2 D M i nade q ua tely c o ntr olle d o n 
m etfor m i n a n d, if c o n d ucte d, to 
n o n- dia bet ic o b es e p artici pa nts.

P F - 0 7 0 8 1 5 3 2 plas ma P K par amet ers*
A U C 2 4, Cma x , T m a x, t½ o n Da y 1 a n d 
f ollo wi n g m u lti ple, oral d ose
a dm i nistratio n, as data pe r mit.

T o c haracterize t he u rin e P K of 
P F- 0 7 0 8 1 5 3 2 f o ll o wi n g mu ltip le d o ses
a d mi nistere d orall y t o ad ul t partici p a nts
w it h T 2 D M
i na de quate l y c ontr oll e d o n
me tfor mi n .

U ri ne P K pa ram eters* f or 
P F - 0 7 0 8 1 5 3 2, as data per mit : A e 2 4, 
Ae 2 4%, a nd C Lr f ollo wi n g m ulti p le,
o ral d os e a d mi nistrati o n, as data 
per m it. 
 
 
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 5
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Par a meters are d efin e d i n T a ble 1 1 , T a ble 1 2 , Ta ble 1 3 a n d/ or A p pe n di x 8 : A b bre viati o ns.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 6
4. S T U D Y D E S I G N
4. 1. O v er all Desi g n
T h is is a ra n d omize d, d o u bl e- bli nd ( i n vestiga t or- a n d pa rticipa nt -bli n d ), s po ns or- o pe n , 
p laceb o -c o ntr olle d, m ulti ple o ral dose-e scalatin g st ud y of P F - 0 7 0 8 1 5 3 2. 
T h ere m a y b e 2 par ticip a nt p o p ul ati ons e nr oll e d i n t his stu d y : partici pa nts e nroll i ng wit h 
T 2 D M (as i n dicate d b y  H b A 1 C le vel at scree nin g, s ee S ectio n 5 ) a n d n o n- d ia betic obes e 
p artici pa nts (as i ndic ated b y  B MI at scree ni ng, se e Secti o n 5 ). T he st u d y will be c on d ucte d
i n up t o 3 par ts, p ort io ns o f whic h ( see S ecti o n 4. 3 ) ma y  be co n d ucte d c o n c urre ntly.
P art A : ad ult pa rtici pan ts wit h T 2 D M i nade q u atel y c on tro lle d o n metf or m in w h o wi ll 
recei ve P F - 0 7 0 8 1 5 3 2 or p lace bo dail y f or 2 8 d a ys.
U p t o 5 s uc h c oh o rts wi ll be e nr o lle d,
wi t h ap pr o xi m atel y 1 0 p a rticipa nts (8 P F- 0 7 0 8 1 5 3 2: 2 pla ceb o) per c o h ort.  F or i n di vi d ual 
pa rtici pa nts i n Part A, th e d urat i on of t he stu d y fr om t he Scree ni n g v isit t o t he o n-site 
fol l o w-u p vis it w ill be ap p r o ximate l y 1 0 wee ks of w hich ap pr o x i matel y 3 3 da y s will be 
i n patie nt at t he C R U.
P a rt B ( opti o n a l): o bese ( no n d ia betic) a du lt p articipa nt s w ho will recei ve P F - 0 7 0 8 1 5 3 2 or 
pl ace bo d ail y for 4 2 d a y s. This i s a n o pti onal st u d y pa rt f or whic h u p t o 2 c o h ort s ma y b e
e nr olle d wi th a p pr oxi m atel y 1 5 o bese par ticip a nts (1 2 P F - 0 7 08 1 5 3 2 : 3 pla ce bo) p er c oh ort.
 
F or in di vi d ual p artici pa nts i n Part B , t he d ura ti o n of t he st u dy fr o m t he
Scree ni n g v isit t o the o n -site f oll ow - u p visit wi ll be ap pr o xi matel y 1 2 w ee ks o f w hic h
ap pr o xi ma tel y 4 8 d a y s will be i n patie nt at t he C R U.
P art C ( opt io n a l): a d ult partici pa nts wit h T 2 D M i n a de qu ately c ont r olled o n metf or mi n w h o 
wi ll receive P F- 0 7 0 8 1 5 3 2 or pl ace b o dai ly f or 4 2 da y s.
U p t o 2 c o hort s o f 1 0 p artici pa nts 
( 8 P F- 0 7 0 8 1 5 3 2: 2 p lace b o pe r c oh ort ) m a y be e n r olle d if j ud ge d nec essar y t o meet t he stu d y
o bjecti ve s. F o r in di vi d u al p articipa n ts i n Part C, t he d ur ati o n of t he st ud y fr o m t he Scree ni n g 
visi t to t he o n -site foll o w - u p visit will be a ppr o xi mat el y 1 2 wee ks o f w hic h a p pr o xi matel y 
4 7 d a ys w ill be i n patie nt at t he C R U.
In all st u d y  parts, partici pa nts will i nitiall y ret ur n t o t he cli nical researc h u nit (C R U) 7 t o 
1 4 da y s after t he last a d mi nistrati o n of I P f or a n o n -site foll o w - u p visit. A f urt her f oll o w - u p 
c o ntact wit h partici pa nts will be c o n d ucte d at least 2 8 da y s a n d u p t o 3 5 da y s after the last 
a d mi nistrati o n of I P; t his co ntact m a y  be d o ne via a p h o ne call.
T he st u d y will be c o n d ucte d i n t he U S.  W h ere m o re t ha n 1 site particip ates i n a gi v e n
c o h ort, an attem pt w ill be m a de t o ha ve at least 1 partici pan t ran d o mi ze d to pl ace b o per
pa rtici patin g site, whic h w ill be fac ilitated t hr ou g h b l oc k ra nd o m izati on.   Part ici pa nts w h o 
d isc o nti n ue p rior t o c om pleti o n o f t he st u d y ma y b e rep lace d, at t he discreti o n of t he 
p ri nci pal i n vesti gat or (PI) a n d s p o ns o r.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 7
4. 2. Sc ie ntific R at i on a le f or St u d y D esi g n
T he pri m ar y p ur p o se of this st u d y is to e val uate th e safety, t olera bilit y, a n d P K of m ulti ple
escalatin g oral d os es of P F- 0 7 0 8 1 5 3 2 i n a d ult pa rtici pa nts wit h T 2 D M.  
4. 2. 1. P o p ul ati o n (s)
T he p o p ula ti o n plan ne d f o r t his stu d y w ill be male a n d fe male a d ult partici pants . Fe male
parti ci pa nts will be w o m e n of n o n-c hild be arin g p o te ntial (W O N C B P), si nce at t he pr ese nt
ti me em br y o fetal d e v el o p ment t o x icity stu di es wit h P F - 0 7 0 8 1 5 32 ha ve n o t bee n c o n d ucte d.
I n male participa nts a p pro pri ate meas ures ar e e x p ecte d t o be foll o we d t o lim it p ote ntia l 
tra nsfer of P F- 0 7 0 8 1 5 3 2 i n s e men t o par t ners (see A p pe n d i x 4 ).
Pa rticipa n ts e nr olle d in t his stu d y will be a d ult s wit h ina de q uate l y c o ntr olle d T 2 D M (as 
i n dicated b y H b A 1c at scree ni n g) o n metf or mi n m o n ot hera p y , w hic h is co ns i dered first-li ne
t hera p y fo r gl yce mic co ntr ol accor d i n g t o c u rre nt treatme nt g u i delines. 1 1 At screen i ng, t his 
st u d y re quires t ha t par tici pa nts ha ve bee n taki n g a mi n im u m sta bl e met for mi n d ose of at least 
5 0 0 m g/ da y  f or at least 2 m o nt hs p ri or to t h e scree nin g vis it.
T he d ose of metf or mi n, w here 
p ossi ble , is e x pec ted t o re mai n t he same u n til c om p letio n of stu d y par tici pati o n (ie, f oll o w-u p 
visit ). A vai la ble i n vitr o da ta s u g gest t hat P F -0 7 0 8 1 5 3 2 is n ot e x pect ed t o i m pa ct th e P K of
metf o r mi n via i n hi biti o n o f or ga nic cati o n tra ns p orter ( OC T ) 2, an d t h e ris k of a cli nical
i nteracti on is dee me d ne g lig i ble.
T her e is p rece de nt f or a G LP - 1R a g o nist be i ng in d icated f or o be sity ( Sa xe nd a ® , lira gl uti de
3 m g) .  P F- 0 7 0 8 1 5 3 2 ma y als o be a ssesse d i n n o n- d iabe tic o bese par tici pants i n this st u d y. 
T his w o u ld af f ord t h e o p po rt u nity t o assess t he safety, t olera bility, p h armac o ki n etics,
 
i n a n obe se p o p u latio n. T he P K
dat a colle cte d i n 
these c o h o rts ma y be u s ed t o s elect d oses a n d titrati o n al gor it hm s fo r f ut ure st u dies o f 
P F - 0 7 0 8 1 5 3 2 i n o b esit y.
 
 
 
 
 
 
 
4. 2. 2. I P A d m i nistr ati o n
T he t ot al dura ti o n of d osi n g f or P F- 0 7 0 8 1 5 3 2 or pl ace b o i n t his stu d y  will b e u p t o 4 2 da ys , 
as su p p ort e d b y c om p leted n o n cli nical to xi cit y st u dies (Secti o n 2. 2. 3 ).
All partici pa nts will 
be co nfi ne d t o t he cli nical researc h u nit (C R U ) du ri n g d osi n g peri o ds as d etailed i n t he
S c he d ule of A cti vities.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 8
D u e t o the a nticipate d g astr oi ntesti nal-relate d t olerabilit y  iss ues assoc iated w it h G LP - 1 
a nta go ni s m1 2 that ha ve bee n s ho w n t o toler ate with re pe ate d d os i n g, a d ose titrati o n a pp roac h 
wil l be ta ke n i n this st u d y.  T his ma y n o t be necess ar y f o r all co h orts ( see Secti o n 4. 3. 5 ). 
M ul tiple es calatin g dail y  oral d oses of P F - 0 7 0 8 1 5 3 2 will be ad mi nister e d t o pa rticipa nt s w it h 
T 2 D M f or 2 8 d a y s i n st ud y  Part A . It is e xpe cted t hat t he se c o h orts wi ll re q uire u p t o 
ap pr o xi matel y  2 we e ks of t itrati o n, i n a dditi o n t o at least 1 4 d a y s of d os in g at t he tar get d o se 
le vel. T his d ur atio n is an tici pate d t o be s uff icie nt t o assess safet y, t olera bilit y, P K,
 
 of P F - 0 7 0 8 1 53 2 at eac h d os e escalati o n ste p. H o we v er, if necess ar y t o e nha nce 
t olera bilit y or e nable ex p l orati o n of a wi der d ose r a n ge, the d urat i on o f titrati o n, a nd 
there f ore t he total d ur ati o n of d osi n g , i n pa rtici pa n ts w it h T 2D M, m a y be increas e d t o u p to 
4 2 da y s i n st ud y  Part C .  
I n Part B of t his s tu d y , if c o n ducte d, n o n- d ia betic obese p artici p ants ma y b e enr o lled f or 
4 2 d a ys of d osi n g.   T he d u ratio n of d os e a dmi n istrati on i n t his c oh o rt is base d o n a ntici pate d
ti me nee de d t o t itrate t o hi g her d oses of P F- 0 7 0 8 1 5 3 2 t ha t may b e nee de d t o tr eat obesit y  
 
D o si n g of i n vesti gati onal p r o duc t (I P) is pla n n e d t o occur i n t he fed state, ie, wit h brea kf ast.  
W hile , bas ed o n p h y sic oche m ical pro per ties a nd i n silic o pre di cti o ns, fo o d is n o t e x pecte d t o
h a ve a sig n ifica nt i mpact o n P F - 07 0 8 1 5 3 2 e x p os u re, if t h o u g ht nece ssary t o ac hieve st u d y
o bje cti ves (e g, to as s ess t olera bilit y or e x p o s ure), t he timi n g of me als or s nac ks relati ve to
stu d y treat ment a d mi ni strati o n ma y be a ltered d u ri n g an y  of t he st u d y c o hort s; s ho ul d t his be
ne cessar y, details will b e pr o vi de d t o i n vesti gat ors in wr itin g.
4. 2. 3. St u d y Bl i n di n g
T o per mit a n u n bi ase d assess me nt of s afety t he p a rtici pa nts’ treat ment as sig n m e nts (acti ve
treat me nt vers us place b o) wi ll be bl i nd t o bot h si te staff (e x ce pt t h ose i n v ol ve d i n pre pa rati on
of d os es) as well as t he st u d y pa rtici pa nts.  H o w ev er, t o per mit real-ti me re vie w o f t he safet y
a nd P K dat a, a li mite d n u mber o f s p ons or st u d y team m e mbers will be u n bl i n de d (see 
Sect i on 9. 5 ).
4. 2. 4. E n d p oi nt s
4. 2. 4. 1. S a fet y
Gi v en t hat t he c urre nt st ud y  is th e first t o a d mi nister re peate d d o s es of P F- 0 7 0 8 1 5 3 2 t o
h u ma ns, a n escalati ng d es i gn wit h ca ref ul on- g o i ng re v ie w of safety a n d P K of P F - 0 7 0 8 1 5 3 2
is pla n ne d . D o ses a n d d ose titratio n sc h e mes (if us ed) i n t he esc alati on se q u e nce m a y be 
m o difie d or re peated as g ui d e d b y e mer gi ng sa fet y, t olera bilit y, a n d P K da t a a n d w ill be 
p r o vi ded t o i n vest i gat ors i n writin g p rior t o i nit iatio n of d os i n g.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 2 9
Cl i nical safety l a b orat or y tests, t h oro u g h ass essme nt s of vital si gns a n d 1 2- l ea d E C Gs,
p h y sical e xami na ti o ns, a n d A E m o nit ori n g will pr o vi de e ssentia l data t o e v al uate t he safet y
a n d t olerabi lity of P F - 0 7 0 8 1 5 3 2.
 
  
W h ile G L P -1 R a g o nists t ypicall y  are n ot asso c iated w it h h y p o gl yc e mia u nle ss
c o-a d mi nistere d w it h a nti- dia betic a ge nts t hat ca n ca use h y p o g l yc e mia (s uch as i ns ulin or
s ulf o nyl u reas), bl o od g l ucose c o n centra tio ns w ill be m o nit o re d thr o u g h o ut the st u d y vi a a 
g l uc ome ter at least o nce d ail y ( pre-brea kfast ), an d caref ul m on it orin g of s ym pt o ma tic
h y p o g l yce mic A Es wi ll be pe rfor me d.
B aseli ne ( Da y - 1) assess me nts w it h ti me-matc he d p r oce d ur es w ill p erm it wit hi n partici pa nt 
c o m paris o ns, as a p pr o p riate. I n a d diti on, place b o-a dj u sted ( bet wee n s u bject) c om pari s o ns of
d ose -res p o ns e w ill als o b e c o n d ucte d. 
I n an eff ort t o red u ce variabi lit y a n d better q u a nti f y a n y p ot e ntial ch a n ges i n h eart rate a nd
b l oo d press ure ( B P) d uri n g t h e stu d y, all meas ure me n ts of E C G a n d vital si g ns ( p ulse a n d 
B P ) will be c ollect ed i n tri plicate (e xce pt as note d in t h e S c he du le of A ctivit ies) a n d th e 
mea n val ues wi ll be u sed f or a nal ysis at eac h ti me p o i nt.  
4. 2. 4. 2. C h ar act eriz ati on of P F - 0 7 0 8 1 5 3 2 P h ar m a c o k i netics
As is t ypica l fo r m ulti p le ascen di n g d ose ( M A D) st udi es wi th i n vesti g ati onal a ge nts, t his
st ud y  will i nc lu de sa m plin g t o e x a mi ne the Da y  1 a n d stea d y -state plas ma P K of
P F- 0 7 0 8 1 5 3 2.
U ri ne sa m ples wi ll also be c ollected a t stea dy-st ate i n Parts A a n d C t o
e valua te t he pr o p orti o n of dr u g e xcr ete d v ia re nal eli mi natio n. 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 0
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
4. 3. J u stific ati o n f or D ose
T h e d oses pr o p os e d for t his st u d y we re det ermi ne d c onsi d eri n g all rele vant i n f or mati on 
o btai ne d fro m n o ncl inic al safety stu dies al on g wit h pre li minar y safet y, t olera bilit y, a n d P K
dat a o bser ve d in t he o n g o i n g S t ud y  C 39 9 1 0 0 1 .  
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 1
 
 
 
 
 
 
  
 
 
 
 
4. 3. 1. D os e S electi on -- P art A
I n Part A of t his st u d y, a starti n g d ose o f 1 0 m g Q D P F - 0 7 0 8 1 5 3 2 is pla n ne d .  
 
 
 
 
 
D ue t o p ote ntia l to lerati o n of gastr oi n testinal a dvers e eve nts t hat ha ve bee n s h o w n t o occur
w ith G L P- 1 a g o nists, d o s es of P F -0 7 0 8 1 5 3 2 wi thi n a c o h ort m a y be titrate d fr o m a l ow d os e 
u p t o t he tar get d ose t hat is e x pecte d t o be o b tain e d b y t he c o ncl usio n of t he d osi n g p erio d.
Be y o n d t h e starti ng d ose. t he pla n ne d d ose escalati o n pr oce d ur e will be dict ate d b y t he r ules
s u m marize d i n Secti o n 6. 6. 1 a n d is ai me d t o oc c ur i nitiall y in i ncre me ntal i ncreas es of
a p pr oxi mate l y ≤½-l og ( i e, a p pr o xi matel y 3. 3-f ol d) base d o n pre dicte d e x p o s ure. T hes e 
in cre me nts m a y  be a dj uste d ba sed o n e mer g i n g safety t olera b ilit y a nd P K data. 
D ose -escalatio n is e nvisi o n e d t o pr ocee d u p t o t he hi g h est d ose d ee me d t o be well tolerate d 
wit h a n acce ptable safet y pr ofile, ac hie ve me nt of plas ma e x p os ures e q u i vale nt t o t he PK
st o p pi n g li mits (see Se cti o n 6. 6. 1 ).
4. 3. 2. D ose Selecti o n -- P art B
Pa rt B i n o be se n o n- dia betic par ticipa nts is o pti o n al.  D o si n g in Part B m a y oc c ur after data 
fr o m at least 2 c oh orts i n Pa rt A are revie w e d b y t he st u d y tea m (Da y 2 8 s a fety , Da y 1 4 or
2 1 P K) . Part B of the st u d y e nro lls a differe n t po p ul ati o n t hat ma y ha ve a differe nt
t olerab ility p r ofile relati ve t o T 2 D M a n d all o ws f or a l on ger t itrati o n peri o d t ha n Part A ( up
t o 6 wee ks) .  T his m a y  aff ord t he o p p o rt u nity t o ac hie ve h i g her tar get d oses i n Part B .  T h e
target d o se i n P art B ( C o h ort 1) w ill be n o gr eater tha n a p pr o xi matel y 3. 3-f ol d hi g h er t ha n a
d ose pr e vi o usly teste d i n t he st u d y t hat was d e e me d t o be ade q uatel y t olerated a n d h as 
e x p os ures pr oje cte d t o be less t han t he PK st o p pi n g li mits. D o ses in Part B are ex pe cted t o 
b e titrat e d t o t he tar get d ose o ve r t he 4 2 d a ys of t he treat me nt p eri o d.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 2
4. 3. 3. D o se Se lecti on -- P art C
Pa rt C i n T 2D M is o pti o n al.  D o si n g i n Part C ma y occ ur after dat a fr o m at least 2 c o h orts i n 
Pa rt A are re view e d b y t he st u dy t ea m (Da y 2 8 s afety, Da y 1 4 o r 2 1 P K ).  Part C of t he st u d y  
all o ws f or a l on ge r titrati o n peri o d ( u p t o 6 we e ks) a n d t heref ore ma y all o w f or attaini n g 
hi g her ta r get d ose s i n Part C, relative t o Part A.  T he tar ge t d ose i n Part C ( C o h ort 1) will be 
n o gre ater t han a p pr oxi mate l y 3 . 3-f ol d hi g h er tha n a d ose p re vi ousl y teste d i n t he st u d y that 
w as d ee me d to b e a de q u ately t olerate d a n d h a s e x p os ures pr o jecte d t o be less t ha n t he P K 
st o p pi n g li mits.  D oses in Pa rt C a re e x pecte d t o b e titrate d t o the tar get d o se o ver t he 4 2 d a y s 
o f th e treat me nt p e ri od.  
4. 3. 4. D ose R a n ge a n d M ar gi ns
T h e pla n ne d d o se ra ng e for t his st ud y ( 1 0- 3 0 0 mg Q D , b ut wit h t he p o tent ial t o escalate u p 
t o 1 0 0 0 m g Q D de p e n di n g u p o n o b ser vati ons a t l o wer d oses) was c h ose n i n o r der t o 
a p pr o priatel y b rac ket t he pr ojected ef ficaci o us dos e t o c ov er t he pote n tial i m pact of
u nce rtai nty i n pr ojecti o n of e fficaci o us c on c e ntrati o n or of u na ntici pate d f actors o n d r u g 
e x pos ure, w hil e acc o mm o dat i n g feasi bilit y c o nsi derati o ns. 
  
Pr e dicte d e x po s ure le vels a n d safet y ma rgi n s f or a ran g e of anti ci pate d d oses f or t his st u d y 
are pr o v i de d in T a ble 8 b e l o w.  All e x pos ure -b ase d safet y ma r gi ns were cal c ulate d usi n g 
u n b o u n d c o n ce ntrati o ns.  T his table gi ves an o ver vi e w of t he po te ntial d o se le vels; h owe v er,
d oses ma y  be a dj u ste d as l o ng as t he t he pr ojec te d i ncre me nt of C m a x a n d A U C 2 4 be t ween
d os e le vels is n o greater t ha n ap pr o xi ma tel y 3. 3-f ol d a n d t he pr oj ecte d e x p os ure is n ot 
e x pecte d t o e xcee d t he P K st o p pi n g li mits .
It is a ntici pated t hat d ose titrati on w ill be req uire d i n t hi s stu d y; detai ls are pro vi de d i n 
Se ctio n 4. 3. 5 .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 3
 
 
 
 
 
4. 3. 5. D ose T itr ati o n
T he d ose titrati o n sc he d ule f or eac h c o h ort will be pr o vi de d i n writ i n g pri or t o its i nitiati o n.
St u d y P art A : it is e x pected t h at t hese co h orts will re q uir e up t o 2 wee k s of titrati on,
f oll o we d by at least 1 4 d a ys of d o sin g a t t he tar get d ose le vel. A sam ple d ose titrati o n
sc heme is pr o vi d e d i n Ta ble 9 f or illustrati ve p ur p os es o nl y. T he d ose le vels a n d d ose 
titrati on sc hemes o u tline d i n Ta ble 9 m a y  be m o d ifie d ba se d on t he emer gi n g safet y, 
t olerabil it y, or P K data. A d diti o nal titrati o n sc he mes, i ncl u di n g u p t o 4 w ee ks of d ose 
titrati o n wit h o u t a stable d o si n g peri o d at a tar get d o se le vel, m a y  be e x pl ore d. T he t otal
d urati o n of d ose a d mi nistrati o n t o a n y gi ve n p articipa n t i n Part A will n ot e xce e d 2 8 da ys . 
St u d y P art s B a n d C : t he titrati o n sc he me t o be use d i n Parts B a n d C will be det er mine d
base d o n da ta e mer gin g fr o m Pa rt A a n d ma y  or ma y n o t in cl ude a sta ble d o si n g peri o d. T he
t otal d urati o n of d os e a d ministra tio n t o a n y  gi ve n parti ci pa nt i n Part s B or C will n ot e xc ee d 
4 2 da y s.
D uri n g th e titrati o n p eri o d, if a pa rtici pa nt d oe s n ot t olerate titrati o n to t he ne xt d os e le vel, as
dete r mi ned b y t h e i n vesti gato r a nd wit h n otificati o n t o t he sp o ns or, t he partici pa n t may b e 
re verte d t o t he pr e vi ousl y t olerate d d ose le v el, a n d dose titrati o n to t he ne xt hi g her d os e m a y
be dela y e d b y 1 t o 2 d a y s or l o nger, as n ee de d. F oll o wi n g d o w n -titrati o n, 2 se parat e atte m pts 
at u p-titrati o n t o t he ne xt d ose le vel are per mitte d, per i n vesti gat or discreti o n .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 4
If, per i n vesti gato r assessme nt, u na cc e pta ble i nt olera nce (e g, se v ere v omiti n g) occ urs s h ort ly 
f oll owi n g d os e ad mi nistr ati o n, t he d ose will n ot be re -ad mi n istere d an d t he partici pa nt m a y
res u me d osi ng at t he c urre nt d ose le vel at t he n e x t sc he d ule d dosi n g tim e. Partic i pa nts w h o se 
d ose le vel is tole ra bilit y-limit e d ma y  c o ntin ue i n t he st u d y f or the i nte nde d d ura ti on of t h eir 
assig ne d c o h ort at t heir o w n i n divi d ual ma xi m u m t olerate d d o se (M T D ), as j ud ge d t o be 
a p pr o priate b y the PI  a n d s po ns or . F or C o h o rts wi th a sta ble d osi ng p erio d , dose 
adj u st me nts/titrati o n will n ot be p er mitte d d u ri ng t his pe ri od a n d pa rtici pa nts s h oul d r emai n
o n t he sa me d os e (e ven if l o wer t ha n t he tar get d ose ).
T a ble 9. 
S a m ple Tit r ati o n Sc he me a n d D o si n g Par a di g m for S t u d y P a rt A
C o h or ta
St u d y D a y
1 
2 
3 
4 
5 
6 
7 
8 
9
1 0 
1 1 
1 2 
1 3 
1 4
1 5 t hr o u g h 2 8 b
1
1 0 m g
1 0 m g 
1 0 m g
1 0 m g
1 0 m g 
1 0 m g
1 0 m g
1 0 m g
2
1 0 m g 
1 0 m g
2 0 m g 
2 0 m g 
3 0 m g 
3 0 m g 
3 0 m g
3 0 m g 
3
1 0 m g
2 0 m g
3 0 m g
4 0 m g 
5 0 m g 
6 0 m g 
8 0 m g
1 0 0 m g o r M T D c
4
1 0 m g
3 0 m g
5 0 m g 
8 0 m g 
1 0 0 m g
1 2 0 m g 
1 5 0 m g
2 0 0 m g or M T D c
5
1 0 m g
3 0 m g
5 0 m g
1 0 0 m g
1 5 0 m g
2 0 0 m g
2 5 0 m g
3 0 0 m g or M T D c
N O T E t h at this is pr o vi de d a s a sa mple o n l y. Ot her t ha n f or Part A, C o h ort 1, t he titratio n sche m e a n d ta r get 
d os e le vel f or eac h c o h ort will be pr o vi de d t o t he i n vesti gat or(s) i n wr itin g p ri or t o i nitiati o n of eac h c o h ort. 
a.
D os es a nd d ose titrati o n a p pr oac hes f or a d diti o nal c o h orts/st u d y parts t o be deter mi ne d.
b.
Sta ble d o se t o be a d mi n istere d fr o m at least Da y 1 5 t hro u g h 2 8 .
c.
F or p artici pa nts n ot a ble t o reac h t o target d o se o f t hat c o h ort, t he i n di vi d ual M T D
f or tha t partic i pant ma y 
be p er mitte d.
F or all d osi n g a n d titrati o n re gi me ns, matc hi n g plac e b o will als o be a d mi nistere d.
 
 
 
 
 
 
 
 
 
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4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last scheduled procedure shown in the Schedule of Activities.
The end of the study is defined as the date the investigator reviews the last participant’s final
data and determines that no further evaluation is required for the participant to complete the
trial.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants must be between the ages of 18 and 70 years, inclusive,
at the time of signing the informed consent document (ICD). Females must be of
non-childbearing potential.
•
Refer to Appendix 4 for reproductive criteria for males (Section 10.4.1) and 
females (Section 10.4.2).
Type of Participant and Disease Characteristics:
2. Parts A and C only: Participants enrolling with T2DM must be taking metformin
monotherapy as their only anti-hyperglycemic treatment. Metformin dose must be at
least 500 mg per day and must be stable, defined as no change in the treatment, 
including dose, for at least 2 months prior to the screening visit. For further 
information, see Section 6.5.
3. Parts A and C only: For participants enrolling with T2DM: HbA1c ≥7.0% and
≤10.5% at screening (confirmed by a single repeat, if necessary).  
Part B only: For participants enrolling as non-diabetic obese: HbA1c <6.5% at 
screening.
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PFIZER CONFIDENTIAL
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4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
5. A total body weight >50 kg (110 lbs).
6. Parts A and C only: For participants enrolling with T2DM: body mass index (BMI)
of ≥24.5 to ≤45.5 k/m2.
7. Part B only: For participants enrolling as non-diabetic obese: BMI >30.5 to
≤45.5 kg/m2.
Informed Consent:
8. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or
allergic disease (including drug allergies but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
•
Participants who have chronic conditions other than T2DM and obesity (for 
example, hypercholesterolemia or hypertension) but are controlled by either diet 
or stable doses of 2 or fewer medications may be included (for example, a
participant with hypercholesterolemia on appropriate treatment is eligible).  See 
Section 6.5 for further information on concomitant medications.
2. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes.
3. Part B only: Participants enrolling as non-diabetic obese may not have medical
history of type 2 diabetes mellitus.
4. Evidence or history of clinically significant cardiovascular disease. In particular, 
history of myocardial infarction, unstable angina, arterial revascularization, stroke,
New York Heart Association Functional Class II-IV heart failure, or transient
ischemic attack within 6 months of screening.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 7
5.
A n y  malig n a n c y n ot c o nside re d c ure d (e x ce pt basal cell carcin o ma an d s q u a m o us cell 
carci no ma o f t he sk i n); a p artici pa nt is c o nsi dere d c ure d if t he re ha s b e e n n o e vi de n ce 
o f cancer r ec urre nce i n t he pre vio us 5 ye ars.
6.
A c ute pa n c reatitis or hi stor y of c h r o nic pancr eatitis.
7.
A c ute gal l bla dd er dis ease. 
8.
A n y c on d itio n p os si bly affe cti ng dr u g a bs or pt i o n (e g, pri o r bariatric su r ger y, 
gast rect o my , or a n y a r ea of i ntestinal resectio n, act i ve i nfla m mat or y b owe l disease or 
pa n creatic i ns ufficie nc y).
9.
Pers o nal or famil y  hist or y of m e d u llar y t h yr oid ca rcin o ma (M T C)
or m u lti ple 
e nd o crine ne o p lasia s y ndr o me t y p e 2 ( ME N 2) , or partici pa nts w it h sus pe cted M T C 
pe r t he i nv esti gat or’s j ud ge m e nt.
 
1 1. O t her ac ute or c hr o nic medi cal or psyc hi atric c on diti o n i ncl u d i n g recen t (wit hi n t he 
pa st ye ar) or act i ve s uicidal i deatio n o r beha v i or o r la borat or y a b n o r malit y t hat m a y
i ncrease t he risk associ a ted w it h stu d y p artici patio n or I P a d mi nistrati on o r ma y 
i nterfere wit h the i nt er pretati o n of stu d y  res ults a n d, i n the j ud g me nt o f t he 
i n vesti gat or, w o ul d ma ke t h e par ticip ant ina p p r o priate for e n try i nt o t h is stu d y .
P ri o r/C o n c o mit an t T her a p y:
1 2. See i ncl usi o n criterio n # 2 , e xcl usio n criteri o n # 1 a n d Secti o n 6. 5 f or details o n
c o nc o m ita nt me dicatio ns. 
P rior/ C o n c urrent C lini cal St u d y E x p erien ce:
1 3. Pre vi o u s ad mi nis tratio n wit h a n in v estiga ti onal d r u g wit hi n 3 0 da ys ( or as determi ne d 
b y  t he local req ui r eme n t) or 5 half- live s precedi n g t he first d ose o f I P use d i n t his 
stu d y ( whi c hev er is lo n ger) .
1 4. K n o w n pr i or par tici pati o n (ie, ran d o miz ed a n d receive d at least 1 d o se of 
i n vestigati o na l pro d uct ) i n a trial i n v ol vi n g P F- 0 7 0 8 1 5 3 2 .  N ote t hat a gi ve n 
i n di vi d ual ma y o nly p artici pate i n 1 C o h o rt/ Part of t his st u d y . 
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Diagnostic Assessments:
15. A positive urine drug screen at screening or admission. Participants who have been 
medically prescribed benzodiazepines and report the use of these drugs to the 
investigator at the screening visit may be allowed to participate if approved by the
sponsor.
16. Positive testing at screening for human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B surface
antibody (HBsAb) or hepatitis C antibody (HCVAb).  As an exception a positive
HBsAb due to hepatitis B vaccination is permissible. 
17. Screening supine blood pressure (BP) ≥160 mm Hg (systolic) or ≥100 mm Hg
(diastolic) following at least 5 minutes of supine rest. 
If BP is ≥160 mm Hg (systolic) or ≥100 mm Hg (diastolic), the BP should be
repeated 2 more times and the average of the 3 BP values should be used to determine 
the participant’s eligibility.
18. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant
abnormalities that may affect participant safety or interpretation of study results 
(eg, baseline Fridericia-corrected QT [QTcF] interval >450 msec, complete left
bundle branch block [LBBB], signs of an acute or indeterminate-age myocardial
infarction, ST-T interval changes suggestive of myocardial ischemia, second- or 
third-degree atrioventricular [AV] block, or serious bradyarrhythmias or 
tachyarrhythmias).  
If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 
2 more times and the average of the 3 QTcF or QRS values should be used to
determine the participant’s eligibility.  Computer-interpreted ECGs should be
overread by a physician experienced in reading ECGs before excluding participants.
19. Participants with ANY of the following abnormalities in clinical laboratory tests at
screening, as assessed by the study-specific laboratory and confirmed by a single
repeat test if deemed necessary:
•
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 
≥1.5 times the upper limit of normal (ULN);
•
Total bilirubin level ≥1.5 times the ULN; participants with a history of Gilbert’s
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ULN;
•
TSH > ULN;
•
Fasting C-peptide <0.8 ng/mL;
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 3 9

Se r u m calcito n i n > U L N;

A m yl ase > U L N;

Li pas e > U L N .
2 0. P arts A a n d C ( partici pa nts wit h T 2 D M ): Fa sti n g bl o o d gl uc ose > 2 7 0 m g /d L at
scree nin g or a d missi o n , c o nfir me d by a si n gle re pe at test if dee med neces s ar y.
2 2. At Scre e ni n g, p artici pa nts wi th a n esti mated gl o m e r ular filtrati o n rate (e G FR)
< 6 0 m L/ m i n/ 1. 7 3 m2 as calc ulate d b y t he m o d ificati o n of die t i n re nal disease
e qua ti o n (M D R D, see A p pe n di x 2 : Cli ni cal La b orat or y Tests), a n d c onfir me d via a 
si ngle re peat, if dee m e d n ecessar y.
Ot her E xcl us i ons:
2 3. H ist or y of alc o h ol ab u se or bi nge d rin ki n g a n d/ or a n y illicit dr u g use or d e pe nd e nc e 
wit hi n 6 m o nt hs of S creeni n g.  Bi n ge dr i n kin g is defi ne d as a patter n of 5 ( male) a n d 
4 (fe male) or m o re alc o h olic dri n ks i n ab o ut 2 h o u rs.  As a ge n eral r ule, alc oh o l 
i nta ke s h o ul d not e x c ee d 1 4 u nit s per we e k ( 1 u nit = 8 o u nc es ([ 2 40 m L ] beer, 1
o u nc e [3 0 m L ] of 40 % s pi rit or 3 o u nc es [9 0 m L] of w i ne).
2 4. B l o o d do nati o n (e xcl u di ng plas m a d o nati o ns) of a p pr o x i matel y 1 pi nt ( 5 00 m L ) or 
m ore w it hi n 6 0 da y s pri or t o d os i n g.
2 5. Hi stor y of se nsiti vit y t o hepar i n or h e par i n-i n d uce d t hro m b oc y t o pe nia, if he pari n is 
use d t o fl ush I V cat he ters.
2 6. K n o w n i ntol era nce t o an y G L P -1 R a g o ni st.
 
 
2 8. U n willi n g or u na ble t o c om pl y wit h t h e criteria i n t he Li festyl e C o n side ratio ns
secti on of t his pr ot o c ol, i ncl u di n g restricti o ns o n caffei ne, alc oh ol a n d t o bac co use.
2 9. I n vesti g ator si te staff me m bers d irectl y i n vol v ed i n t he c on d uc t of t he stu d y  a nd t heir 
famil y me m bers, site staff me m b ers othe r wise s up e rvise d b y  the i n ves tigat o r, or
Pf izer e m plo y ees, i ncl udi n g t h eir famil y  me m bers, dire ctl y i n v olve d in t h e co n d uc t of 
t he st u d y.
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 0
5. 3. Lifes t yle C o n side r atio ns
T he f oll owi n g g ui d e li nes are pr o v i de d:
5. 3. 1. Me als a n d Diet ar y Re stricti o ns

Pa rticipa n ts must a b stai n fr o m all f o od a n d d ri nk (e xce pt wa ter) at least 8 h o urs pr i or
t o t he first bl o o d sa m ple at t he o ut pat ie nt Scree ni n g a nd f oll ow - u p vis its. 

Partici pa nts are re q uired t o f ast f or 4 h o urs ( e x ce pt wa ter) pr i or t o a d missi o n t o C R U.

P artici pa nts m ust a bstai n fr om all f o o d a n d drin k (ex c e pt wa ter) at least 8 h o urs pri or
t o the fi rst bl o o d sa m ple o n i n patient st ud y  da ys [eg, for fin gers tic k bl oo d gl uc ose 
( FS B G), safety la b o rat ory, P K, 
assessme nt ].

N o nc af fei nate d dr i n ks (ex c e pt as i n dicate d be l ow) ma y be c o n s ume d w ith mea ls a n d
t he ev e ni n g snac k.   

Par tici pa nts wil l refrai n fr om c o ns u min g re d wi n e, g rape fr uit, or
gra pe fr uit-relat e d citr us fr uits (e g, Se vi lle or a n ges, p o me l os, fr uit j uices) fr o m 
7 da y s pri or t o t he first d ose of i n vesti gati o na l pr o d u ct u ntil c oll ectio n o f the fi n al 
P K b l o o d sam pl e.

T he i nitial cal oric i nta ke/ me n u assi g ne d t o eac h participa n t w ill be b ased o n t he 
Harris Be n edic t f or m ula (se de ntar y lifest yl e; t o be pr o v i de d t o t he site pri or t o stu d y
start) usi n g t he partici pa nt’s b o d y  wei g ht meas u re d at screeni n g.

B rea k f ast wi ll be pr o vi d e d at ap pr o x i matel y 0 8 0 0 ho urs o n eac h in pa tie nt da y:

A stan dar d brea kfast will be p r o vi de d f or c o ns u m pti on a fter d o si ng o n all da ys 
 

L u n c h w ill be pr o vi ded a p pr o x i mately 4 h o urs a fter d osin g (a p pr oxi mat el y
1 2 0 0 h o urs ) a nd a t ap pr o x i matel y t he sa me ti me o n eac h i n patie nt d a y .

Di n n er w ill be pr o vide d a ppr o xi ma tel y 1 0 h o urs after d os i n g (a p p r o ximat el y
1 8 0 0 h o u rs) an d at a p p r o xi mately the s a m e time o n eac h i n pat ient d a y.

A n e ve ni n g s n ac k ma y b e per mitte d at a p p r o xima tely 2 2 0 0 h o urs
. 
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C CI
C CI
C CI
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 1
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 3. 2. Alc o h ol, C af feine a n d T o b a cc o

Pa rtici pant s will a bstai n fr o m alco h ol f or 2 4 h o urs ( or as s pecifie d a b o ve for r e d 
wi n e) p ri or t o a d mi ssio n t o t he clin ical researc h u ni t ( C R U) a n d c on ti nue a bstai ni n g 
fro m alco h ol u ntil c ollecti o n of t he fina l bl o o d sa m ple at t he f ollo w- u p v isit. 
Pa rticipa nt s ma y u n d er g o a n alc o h ol breath test o r bl o o d alco h ol t est at t he discreti o n
of t he i n vestigat o r.

C affei ne -c ontai ni n g p r o duct s, u p t o t he eq ui v alen t of t w o 8- o u nce c u ps of c o ffee per 
da y , will be per mitte d.
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C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 2

H o we ver, p artici pa nts m ust a bstai n fr om caffei ne-c o ntai nin g pr o d ucts for a
mi ni m u m of 2 h o urs pri o r t o all vital si g ns a nd E C G m easure me n ts c o n d ucte d 
t hr o u g h o ut st u d y partici pati o n (fr o m scree nin g t o t he fi nal f oll o w-u p visi t).  

 
 
 

P artici pa nts ma y u se t ob acc o- o r nic otine-c o ntai ni n g pr o d u c ts as per mitte d b y t he 
C R U (e g, d ur i ng s m o k in g b rea ks, or i n sp ecifie d locati o n s).
H o w e ver, s m oki n g ma y n o t be per mitte d w he n it wo ul d i n terfere with t he ti mi n g of 
sche d ul e d stu d y  proce d ure s or d u rin g fre q ue nt sa m pli n g p r oce d ures
In
a ddit io n , par tici pa nts m ust a bst ai n fr o m u se of t obac c o- or ni c oti ne-c o ntaini n g 
pr o d uct s:

F or a m i nim u m of 2 h o ur s pri or to all vital s i gn a n d E C G mea s ure me nts;

F or a mi ni m u m of 2 h o urs p rior t o a nd f ol l owi n g a d mi nistrati o n of i nv esti gati o nal
pr o d uct .
5. 3. 3. Act i vit y

Par tici pa nts will a bs tai n fr o m stre nu o us e x ercise (eg, h e a v y lifti ng, w ei g ht traini n g, 
calist he nics, aero bi cs) f or at least 4 8 h o urs p ri or to eac h bl o o d c olle cti o n for cli nical 
lab o rat or y tests.  Wa l kin g at a n orm al pa ce w ill be p er mitte d.

T o sta n dardiz e t he c o n diti o ns o n P K sa m pli n g da ys, par ticip a nts wi ll be re q uired t o
refr ai n fr o m l yi n g d ow n (exce p t w he n req uir e d f or B P, p ulse r ate, a n d E C G
me asu re me nts), eati n g, a nd dri n k i n g b e v era ges othe r t han wa t er d uri n g the f irst 
4 h o urs after d o si n g.
5. 3. 4. C o ntr a ce pti o n
T h e i n vesti gator or hi s or her desi g nee, i n c on s ultatio n wit h t he ma le p articipa n t, will c o nfi r m
t hat t he pa rticip a nt has s electe d an a p pr o priate met h o d of c o ntrace ptio n f or t he i n di vi dual
ma le pa rtici pant a nd h is par t ner(s) fr o m t he p er mitte d list o f co nt race pti o n meth o ds (see 
A p pe n di x 4 , Secti o n 1 0. 4. 4 ) a n d wi ll c o nfirm t ha t the pa rticipa nt h as b e e n i nstructe d i n its 
c o nsistent a n d c orre ct use . At ti me p oints i n di cate d i n the S c he d ule of A c ti vities, t he
i n vestigat or or d esi g nee wil l i nf orm t he male parti ci pa nt of t he ne e d to use effecti ve
c o ntrace pti on c o n sistentl y  a n d c orrectl y a n d d oc u m e nt t he c on ve rsati on a n d the male 
parti cipa nt ’s affir mati on i n t he pa rticip a nt’s ch a rt ( partici pan ts ne e d to affi rm t heir c onsi ste nt
a n d c orr ect u se o f at least 1 of t h e select e d met h o ds of c o ntr ac e pti o n). I n a d ditio n, t he 
i nve sti gat or or d esi g nee will i nstr uct t he pa rtici pa nt t o call i m me diatel y if t he selecte d
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C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 3
c o ntracept i on me t h o d is di sco nti n ue d o r if p reg n a nc y is k n o w n or s uspe cte d i n t he
pa rtici pa nt’s fe male p art ner.
F e male par tici pa nts will n ot re qui re use of c o nt race ptio n as t he y  can n ot be w o m e n of 
c hil db eari n g p ot e ntial. 
5. 4. Scr ee n F a ilures
Sc reen fail ures are defi n e d as p articipa n ts wh o c o ns e nt t o participat e i n t he cli nical st ud y b ut
are n o t su bse q ue n tl y r an d o m ly as si gn e d t o i n vestigat io nal p r o du ct/entere d i n t he stu d y. A 
mi ni ma l set of scree n failu re i nfor ma tio n is re q uired t o e n s ure tra ns parent re p orti n g of screen 
failu re partici pant s t o me et t he C o ns o li date d St a n dar ds of R e po rti n g Trials ( CO N S O R T) 
p u bli shi n g re q uirem e n ts a nd t o r es po n d t o q uer ies fr o m re gu lat ory a ut h orities. Mi ni mal 
i nf orma ti o n i ncl u des dem o g ra p hy,  screen f ailu re d etails, eli gi bility criteria, a n d a n y seri ous 
a d verse e vent ( S A E).
I n divi d ual s w h o d o n ot mee t th e criteri a f or partici p ati on i n t hi s st ud y (scree n fail ure) m a y  
n ot be rescree ned,
 
6. S T U D Y IN T E R V E N TI O N
St u d y  i nter ve nti o n is de fi ne d as a n y i n vesti gat i o nal i nter vent i o n(s), markete d pr o d uc t(s), 
pl ace bo, o r me di cal de vice(s) i nte nde d t o be a d mi nistered t o a st u dy p a rtici pa nt accor di n g t o
t he st u dy pr ot o c ol.
F or t he p ur p os es of t his prot oc ol, t he ter m in ves tiga ti o nal pr o d uc t ma y be u se d 
s yn o n y m o us l y wit h st ud y i nter vent i o n.
6. 1. St u d y I nter ve nti o n(s) A d m inist ere d
F or t his st ud y , t he i n vestiga ti o nal pr o du c t is P F- 0 7 0 8 1 5 3 2 ( or matc hi n g place b o).
P F -0 7 0 8 1 5 3 2 a n d m atch in g plac e b o will b e p r o vi d e d b y Pfiz er as b u l k po w de r f or
e x tem p o ra neo u s pre parati o n of o ral so luti o n at t he site. P F -0 7 0 8 1 5 3 2 a n d mat c hin g pl ace bo 
wi ll be pre se nte d to t he p a rticip a nts i n i ndi vi d u al d osi n g c on tain ers.  I n a d diti o n, 
P F - 0 7 0 8 1 5 3 2 a n d matc hi n g p laceb o ma y also b e s u p pli e d b y P fizer as ta blets. If pr o vi d e d, 
ta blets will be s u p plie d to t he C R U i n b ulk al o n g wit h i n di vi d ual dosi n g c o ntai ners f or u nit 
d os i n g.
6. 1. 1. A d m i nistr ati on
O n Da y 1 , partici pa nts wi ll recei ve I P at a p pr o x i matel y 0 8 0 0 h o urs ( p l us or mi n u s 2 h o urs ).  
Deta ils o n meal s a n d d ietar y req uir e me nts a n d acti vity restricti ons a re gi v e n i n Secti o n 5. 3 .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 4
P F - 0 70 8 1 5 3 2 o r al s ol uti o n: I P (ie, P F- 0 7 0 8 1 5 3 2 a n d place b o) w ill be a d mi nistere d 
acc or di n g t o t he e xte mp ora ne o us di s pensi n g rec or d ( E D R). I nvest igat or site pers o nne l will
a d mi nister i n vesti gati on al pr o d uc t wit h a m bie nt te mpe rat ure wat er t o a t otal v o l u me of
a p pro xi mate l y 2 4 0 m L ( 1 0 0 mL i n vestigati o nal pr o d uc t s ol uti on pl us a p pr o xi matel y 1 4 0 m L
ri nse).  T he e ntire v o l ume o f li q ui d m ust be c o ns um e d b y t he p a rtici pa nt.
P F - 0 7 08 1 5 3 2 T a blet f or m ulati o n: I n vesti gator site pers o nne l will a d mi nister i n vesti gati onal
pr o d uc t w ith a p pr o xi ma tel y 2 4 0 m L am b ie nt te m perat ure water.  Par tici pa nts will s wall o w 
t he i nvesti ga ti ona l pr o duct w h ol e, a n d will not ma ni p ul ate or c he w th e in v esti gati o nal
pr o d uct pri or t o swal l o wi n g. 
 
  
Metf or mi n
a n d ot her Per mitte d C o n c o mit a nt Me di c ati ons : O n all st ud y d a y s w hile i n t he 
C R U , partici pa nt s wi ll b e gi ve n t heir m or n i n g d os e of metf or mi n at t he sa me t i me as 
P F- 0 7 0 8 1 5 3 2/ p lace bo .
Pa rtici pa nts wi ll n ot be pr o vi d e d with met f or mi n d uri n g t he st u d y .  Parti ci pa nts enr olle d i n
Parts A a n d C of t his st u d y are e x pecte d t o bri n g t heir c urre nt s u p pl y of metf or m i n pri or t o
co nf i ne me nt to t he u nit .
F or partic ipa nts ta kin g metf or mi n m ore f re q uen tl y t ha n o nce a da y, t he i n vesti gat or will
det ermi n e t he a p pr o priate ti mes d ur i n g t he da y t o a d mi nister t h ose d oses .  F or m etfor m i n 
(req u ire d) a n d o t her per mit te d c on co mit a nt me dicat i ons, t he ti min g of ad mi nis trati o n s h o ul d 
be t he sa me bet wee n i n patie nt da ys , a n d care sh o ul d be ta ke n t o mi ni miz e cha n g es t o t he 
parti cipa nts sta ble me dicati o n r o uti ne.  
6. 2. Pr e par ati o n / H a ndli n g/ St o r a ge/Acc o u nt a bi lit y
1.
T he i nve sti gat or or d esig nee m us t c o nfirm a p pr op riate tem per at ure co n di tio ns ha ve
b een mai nta i ne d d urin g t ransit f or all st u d y i nter ven ti on s receive d a nd a n y
di scre panci es are re por te d a nd r es ol ved b ef ore u se of t he st u d y inter ve n ti on , as 
a pplic a ble for te m pe ratur e- m o n itore d s hi p me nts.
2.
O n l y partici pa nts e nr olle d i n t he s t u d y m a y receiv e st u d y i nter ve nti o n a n d o nl y  
au t hor ize d site staff ma y s u pp l y or a dmi n ister st u d y inte r ven ti o n. Al l st ud y 
i nter ve nti o ns m u st be st ore d i n a secure , e n vir o n mental ly c o ntr olle d, a nd m o nit or e d 
( man u al or a uto m ate d recor di n g ) area i n acc or dan c e wit h t he la bele d sto ra ge
c o n diti on s with acc ess li mite d t o t he i n vesti gator a n d a ut h oriz ed site staff. A t a 
m i nim u m, dai l y mi ni mu m a n d m a xim u m te mperat ur es for all site stora g e loca ti o ns
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PFIZER CONFIDENTIAL
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must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperature since previously documented for all
site storage locations upon return to business.
3. The investigator, institution, or the head of the medical institution (where applicable)
is responsible for study intervention accountability, reconciliation, and record
maintenance (ie, receipt, reconciliation, and final disposition records). All study
interventions will be accounted for using an IP accountability form/record.
4. Further guidance and information for the final disposition of unused study
interventions are provided in the study documentation.
5. Any storage conditions stated in the SRSD will be superseded by the storage
conditions stated on the product label.
6. Study interventions should be stored in their original containers and in accordance
with the labels.
7. See the extemporaneous dispensing record (EDR) for storage conditions of the study 
intervention once reconstituted and/or diluted for administration as an oral solution, 
or the investigational product manual if oral tablets are provided.
8. Deviations from the storage requirements, including any actions taken, must be 
documented and reported to Pfizer upon discovery. The site should actively pursue
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible. Once an excursion is identified, the study intervention
must be quarantined and not used until Pfizer provides permission to use the study 
intervention. It will not be considered a protocol deviation if Pfizer approves the use 
of the study intervention after the temperature excursion. Use of the study
intervention prior to Pfizer approval will be considered a protocol deviation. Specific
details regarding the definition of an excursion and information the site should report 
for each excursion will be provided to the site in the study documentation. 
9. The sponsor or designee will provide guidance on the destruction of unused study
intervention (eg, at the site). If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in
compliance with applicable environmental regulations, institutional policy, and any
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 6
6. 2. 1. P re par a tio n a n d Dis pe nsi n g
Wit hi n t his prot oc o l, pre p arati o n refers t o t he i nv e sti gat or site activitie s perf or med t o m a ke 
t he i nve stigati o nal pr o d uct rea dy f or a d mi nistratio n or dis pe n sin g t o t he pa rticipa n t b y
q ualif ie d staff.  Dis pe nsi n g is d efine d a s t he pr ov isio n of i n vestigati o nal pr o d uct, 
co n c o mitant t reat me nts, a n d acco m p a n y i ng i nfor ma tio n b y q ualif ie d staff me m b er(s) t o a
h ealth care pr o vi de r, p artici pa nt i n acc or da nc e wit h t his pr o toc o l.  Local he alth a u th orit y
re g ulati o ns or i n vesti gat or site gui de li nes ma y use alter nati ve ter ms for t hese activit ies.
P F - 07 0 8 1 5 3 2 a n d p l ace bo or al d osi n g s olut i ons wi ll be pr e par e d i n t he C R U b y  
2 o per at ors, 1 of w h o m is a p h ar macist.  D o ses will be p re pare d b y q u alifie d un b lin de d site
pe rs o n nel.  Bli n de d IP will b e ad mi nis tered t o the pa rtici pant.   D etails of d os e p re parati o n 
wil l be g i ve n i n a s e par at e e x tem p o rane o us di s pen di n g rec or d ( E D R ). Prep a re d d oses wi ll b e 
pr o vi de d in u n it dos e c o n tai ners an d la b ele d in acc o rda n ce wi t h Pfizer reg u latio ns a n d t he
in ves ti gat or site’s la belin g r eq u ire ment s. 
P F- 0 7 0 8 1 5 3 2 a n d pl a ce bo t ab lets, if use d, will be pre pare d at t he C R U i n t he i n di vi d u al 
d osi n g c o nta iners b y  2 o per at ors, 1 of w h o m is a n ap p r opri atel y q ua lified a n d ex pe rie nce d 
me m b er o f t he stu d y  staff (e g, p hys icia n, nurs e, ph y sician’s assista nt, nu rse pr actiti o ner, 
p har mac y assista nt/tec h n ician, o r phar macis t).  T h e ta blets wi ll be pr ovi de d i n u ni t d ose 
c ontai ners a n d la bele d i n acc or da nc e wi t h Pfizer reg ulat io ns a nd t he cli nical site’s label i n g 
re q uire me nts.
 
 
6. 3.
M e asur es t o Mi ni mize Bi as: R a n d o m iz ati on a n d Bli n di n g
6. 3. 1. Al l oc atio n t o I n vestig ati o n al Pr o d uc t
Pa rtici pa nts w ill be ra n d o ml y assi gne d t o recei ve i n vestigat i on al pr o d u ct fr om a cent ral 
ra nd o m izatio n sc he me .  I n vesti gat ors will rema in bl i n de d t o eac h pa rtici pa nt’s assig ne d
i nvest i gatio n al pr od u ct t hr ou g h o ut t h e co urs e of t he stu d y. I n or d er to m ai ntain t his bli nd, a n
ot h er wise uni n v ol ve d t hird part y (f or exa m ple, p ha r macist) w ill be res po ns i ble f or t he
pre parati o n a n d dis pe n si n g o f all in vest igat i onal p r o duct acc or di n g t o t he ra n d omiz ati o n 
sche d ul e a nd assi g ne d tr eatme n t f or t he i n di vid ual part ici pant.
Al l ocati o n of par tici pa nts to trea t me nt g r o u ps wi ll p r ocee d thr o u g h t he us e of a n in teracti ve
res p o nse tec h n ol og y  (IR T) s y ste m (i ntera cti ve W e b-bas e d res p o nse [ IW R] ). T h e u nbli n d e d
di s pe nsi n g pe rs o n nel wi ll b e re q uired t o e nter or s elect i nfor mat i o n incl u di n g b ut n ot li mi te d
t o t he user’s ide n tificati o n (ID ) a n d passw or d, t he p r otoc ol n u m ber, a nd t he part ici pa nt
n u m b er.  T he u n b lin de d d ispe nse r wil l the n be p r o vid e d wi t h a ran d o mi zati on n u m ber, 
p ro d uct assi gn m e nt, a nd dis p e nsab le u nit ( DU) or c o ntai ner n u m ber w he n i n vesti g atio nal
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product is being supplied via the IRT system. The IRT system will provide a confirmation
report containing the participant number, randomization number, and DU or container 
number assigned. The confirmation report must be retained by the unblinded dispenser in the
unblinded site files.  Investigational product will be dispensed at the study visits as 
summarized in the Schedule of Activities.  Returned investigational product must not be 
redispensed to the participants.
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
6.3.2. Breaking the Blind 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
treatment assignment is warranted. Participant safety must always be the first consideration
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s treatment assignment unless this could delay further management of the
participant. If a participant’s treatment assignment is unblinded, the sponsor must be notified
within 24 hours after breaking the blind. The date and reason that the blind was broken must
be recorded in the source documentation and case report form (CRF).
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Blinding codes should be broken only in exceptional circumstances when knowledge of the 
actual treatment code is absolutely essential for further management of the participant. 
Investigators are encouraged to discuss with a member of the study team if they believe that
unblinding is necessary.  When the blinding code is broken, the reason must be fully
documented and entered on the case report form (CRF)/data collection tool (DCT).
Blood specimens will be obtained from all participants for PK analysis to maintain the study
blind at the investigator site.  Only the investigator site staff and blinded study monitor, if 
assigned, will be blinded to study treatment. Other Pfizer personnel will be unblinded to 
participant treatments in order to permit real-time interpretation of the safety and PK data,
and provide information necessary to potentially alter the dose-escalation sequence. The
blinded study monitor, if assigned, will remain blinded to treatment until all monitoring for
the study has been completed. Specimens from participants randomized to placebo will not 
be routinely analyzed for PF-07081532 PK.  To minimize the potential for bias, treatment
randomization information will be kept confidential by Pfizer unblinded personnel and will
not be released to the blinded investigator or blinded investigator site personnel until the
study database has been locked or the investigator requests unblinding for safety reasons.
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6.4. Study Intervention Compliance
Investigational product will be administered under the supervision of investigator site 
personnel.  The oral cavity of each participant will be examined following dosing to ensure
the investigational product was taken.
6.5. Concomitant Therapy
Participants may be on certain concomitant medications that have been prescribed to treat
concurrent diseases such as hyperlipidemia and hypertension. Attempts must be made not to 
alter the doses and regimens of the background/concomitant medications after randomization 
and for the duration of participation in this study. Any changes must be captured in the CRF.
Where applicable, participants are expected to bring their supply of permitted prescription
medications prior to confinement to the unit.
Treatments taken within 28 days before the first dose of IP will be documented as a prior
treatment. Treatments taken after the first dose of IP will be documented as concomitant
treatments. All concomitant treatments taken during the study must be recorded with
indication, daily dose, and start and stop dates of administration. All participants will be
questioned about concomitant treatment at each clinic visit.
Medications, prescription or non-prescription, or herbal supplements not specifically listed
here may be permitted, but only after review and approval by the sponsor.
6.5.1. Medications for Glycemic Control: Parts A and C only
All participants enrolling with T2DM (Parts A and C) are required to be taking metformin
monotherapy. At screening, this study requires (Section 5.1) that participants have been 
taking a minimum metformin dose of ≥500 mg/day for at least 2 months prior to the 
screening visit. The dose of metformin, where possible, is expected to remain the same until 
completion of study participation (ie, the Follow-up visit).
Use of other medications for glycemic control is not permitted in this study (see
Section 6.5.4).
6.5.2. Antihypertensive and Lipid-Modifying Agents: Parts A, B, and C
The use of background antihypertensive and/or lipid-modifying agent(s) is permitted (unless 
noted in Section 6.5.4). Doses of such agents must be stable for at least 4 weeks prior to
screening and are expected to remain the same until completion of study participation 
(ie, follow-up visit).
6.5.3. Management of Nausea and Vomiting
Nausea and vomiting have been reported with administration of GLP-1R agonists. 
Participants experiencing such symptoms may be managed conservatively with bed rest 
and/or fluid management at the discretion of the investigator. If the nausea and vomiting are 
not amenable to conservative management, anti-emetics (eg, prochlorperazine, promethazine,
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 4 9
o n da nsetr o n ) ma y b e a d mi nistere d at t he i n vesti gat or’s discreti o n wit h n otificati o n to t he
s p o nsor a n d e ntr y i n t he C R F .
6. 5. 4. Pr o h i bited Me dic ati o ns
Me di c ati o ns N ot Per mitt ed d ur i ng st u d y c o n d uct
 
 
 
 
Me dic ati o ns N ot P er mitted wit h i n 3 M o nt hs of S creeni n g
T he use of t he f o ll owi n g classes o f age nts is n ot per m itte d wit hi n 3 m o n t hs p ri or t o scree ni ng 
a n d for t he d urat i o n of part ici pati on i n t he st u d y :

T h iaz oli dine d io ne s ( TZ D s) suc h as pi o gli taz o ne a n d r osi glitaz o ne;

S u bc u ta ne o usl y a dm i nistere d a ge nts f or glyc emic c o ntr ol (e g, i ns uli n, e xe natide,
lira gl uti de, praml i nti de).
Me dic at i o ns N ot Per m itted wi t hin 4 We e ks of Scree ni n g
I n ad diti o n t o t he a b ove, the f oll owi n g me dic atio ns are n ot per mitte d wit hi n 4 we e ks pri or t o 
screeni n g a n d f or t he d urat i o n of partici pat i o n in t he st u d y :

Ot her oral a nti - dia betic me dicati ons , i nclu di n g:

S ulf o n y lureas s uc h as acet o he x ami de, c hl or pr o p a mi de , t olaza mid e, tol b uta mi ne ;

Gli me pir i de, gl i pizide, gl y b uri de;

Me g liti nid e a nal o g u es s uc h as rep a glini de, n ate glini de ;

Di pe pti d y l pe pti dase -4 i n hi bit or s (D P P -4i) s uc h as sita g li pti n, sa xa gli ptin;
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P FI Z E R C O N FI D E N TI A L
P a ge 5 0

V ilda gl i pti n;

-gl uc osi dase in hi b itors s uc h as acara b ose, mi glit ol;

S o d i u m- gl ucose c otra ns p orter - 2 (S G L T 2) i n hi bitors s uc h as ca na glifl ozi n.

S ys te mic gl uc oc ortic oi ds suc h as pre d nis o ne, de x a met has o ne, tria mci n ol o ne ,
b u des o ni de, beta met has o ne .
N ote: As a n e xce pti on, stero i d-c o ntai ni n g i n halers, nasal s pra ys, a n d to pi cal
for m ul ati on s are per mitte d .

I m m un o s up p r essa nts s uc h as c ycl os p ori ne an d tacr o li m us.

A p peti te- or wei g ht-m o dif y i n g me dicati o n s, i ncl u di n g n o n-prescri pt i o n or her bals.

P har mac ol o gical a ge n ts wit h a p pro v e d i ndi cati o n f or wei g ht l oss s uc h as o rlistat an d
si b utra mi ne.

( Medica l-gra de) m arij ua na, re gardl ess of me dical i n dicati o n .

A nti- ps y ch otic me dica ti o ns s uc h as ola nza pi ne, ris peri do ne.

A nti de pressa nt me dica ti o ns s uc h as tric yclic a ge nts, selecti ve ser ot o ni n re u p ta ke
i n hi bit ors, a nd ser oto ni n/ n or e pi ne p hrin e re u pta ke in h i bit ors.

C o u mari n-t y pe a nt icoa g u lant s or ot her a ntic oa g ula nt s (e g, dab i gatra n).

A n tic o nv ulsa nt s, if prescri be d f or a seiz ure dis or der.

O pi oi ds .

A ntiarr h yt h mic s.

N o n- selecti ve -b l oc kers.

T hi az i de di uretics > 2 5 m g per da y .

S y m pat h o mi metic a gen ts.
 
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6.5.5. Rescue Medicine
There is no rescue therapy to reverse adverse events (AEs) observed with PF-07081532;
standard medical supportive care must be provided to manage any AEs (see Section 6.5.3
Management of Nausea and Vomiting).
For medical management of hypoglycemia, the investigator may administer oral
carbohydrate, glucagon, or IV glucose according to his or her medical judgment. At a
minimum however, treatment or administration of a scheduled meal should be given if
glucose falls <60 mg/dL for at least 15 minutes, irrespective of whether the participant
exhibits symptoms. Investigators may choose to administer treatment sooner if participants
have bothersome symptoms of hypoglycemia along with glucose values of ≤70 mg/dL.
No rescue therapy will be provided for hyperglycemia. If a participant has sustained elevated
fasting plasma glucose concentrations that are >270 mg/dL on 3 consecutive measurements
over 3 days, that participant will be discontinued, and the investigator will recommend
further appropriate glycemic treatment according to the local healthcare standards and 
national guidelines.
6.6. Dose Modification
6.6.1. Dose Escalation and Stopping Rules 
Dose escalation stopping rules will be used to determine whether the maximal tolerated dose 
has been attained. Dose escalation may be stopped if it is determined that the limits of safety 
and/or tolerability have been reached. This decision will be made after a discussion takes 
place between the sponsor study team and the investigator. The sponsor study team may not 
overrule the investigator’s decision to stop dose escalation.  If dose escalation is stopped 
because of any of these criteria, additional cohorts may receive the same or lower doses of 
the investigational product.
The dose escalation will be terminated based on the following criteria:
•
If 50% or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant laboratory, 
electrocardiogram (ECG), or vital sign abnormalities, in the same organ class, 
indicating dose-limiting intolerance.
•
Severe nonserious adverse events (AEs), considered as, at least, possibly related to
investigational product administration, in 2 participants at a given dose level (but not 
participants receiving placebo), independent of within or not within the same system
organ class, indicating dose-limiting intolerance.
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P a ge 5 2

D osi n g wi ll be p a use d f or a n y seri o us a d verse eve nt ( S A E) t hat occ urs i n a pa rtici pa nt
receivi n g a cti ve treat me nt u ntil ca usalit y is f ull y assesse d by t h e pri nci pal i n ves ti gat or
( PI) a nd s p o ns or.   D osi n g ma y  res u me if t he S A E is deter mi ne d t o b e n o t dr u g -relate d 
b y t he PI an d s p o ns or. If t he S A E is de ter mi ne d t o be eit her dr u g-relate d or 
u n k n o w n, e it her d o si n g will ceas e or t he S A E will be e va l uate d b y t h e s p o ns or’s 
pr ot o c ol rev ie w c o m mittee ( or si milar re view gr o u p), w h ic h is i n de pe n de nt of t he 
stu d y tea m a n d i n vestigat o rs.  If t he prot oc ol re vie w c o mmitt ee deter mi nes t hat 
d osi n g m a y  res u me, a p la n t hat mi tigat es ris ks t o partici pa nt s wit h t he res u m pti o n o f 
d osi n g will be i m plem e nte d.  S uc h a pla n c o ul d i ncl u de a r e visi on of 
i ncl usi o n/e xcl usi o n criteria, re peati n g or re d ucin g t he d ose , or a d di n g a p pr o p riate 
safet y m o nit ori n g . 

It is det er mi ned t ha t the l i mit of s afet y a n d/or t olera bilit y  has been reac hed.   T his 
decisi o n wil l be made f oll o wi n g disc u ssi o ns bet wee n t he st u d y tea m a n d t he 
i n vesti gat or. 

O t her fi ndi n gs t ha t, at the discreti o n of t he st u d y tea m a n d i n vesti gat or, i n dicate t hat 
d ose es calati o n s ho ul d b e halte d.

If, at a n y d ose le vel , t he a vera ge ex p os ure reac hes or e xcee ds t he p harmac o ki neti c 
( P K) st o p pin g li m its of:
T hese st op pi n g li mits are based o n t he u n b o u n d e x p os ures at t h e N O A E L i n t he
n o n- h u m a n pri mate (N H P ) t ox icit y stu d y  (see Secti o n 2. 2. 3 ) after a cc o unti n g f or 
pr otei n bi n di n g i n h u ma ns.

If, base d o n t h e o bser ve d d ata, th e gr o u p mea n ma xi m u m o bser ve d c o nce ntrati o n 
( Cma x ) or area u n der t h e c ur ve ( A U C) (bas e d o n t otal plas ma co nce ntrati o n) of t h e 
ne xt pla n ne d d ose is pr o jecte d to e xce ed t he e scalati on li mits, t hat d ose will n ot be 
e x pl ore d.  M o difie d d ose s m a y be e x plore d i f the y a re n ot e x pecte d t o e xcee d P K 
st o p pi n g criteria.
Pr o g r essi o n t o t he ne xt d o se will occ ur if the las t d ose was well t olerate d a n d after
satisfactor y  re vie w of the a vai la ble safet y a n d P K data.
Data re q uire d f or d os e escalati on e val uati o n will be deter mi ne d b y c o hort a n d will be base d 
o n re vie w of safet y a n d P K data t hr o u g h a mi ni m u m of 1 4 d a y s of d ose a d mi n istrati o n, wit h 
at least 7 of t hese da ys at t he pre vi ous tar get d ose le v el. Eac h d os e escalat i o n will be bas e d 
o n re vie w of a vaila ble safet y a n d P K data f or at least 7 partic i pa nts fr o m that c o h ort. Details 
o n safet y asses sme n ts i ncl ude d i n d ose escalat i o n re vie w are pr o vi de d i n Secti o n 8. 2 a n d 
A p pe n di x 2 .
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The timing of safety and PK required for dose escalation will be provided in writing prior to 
initiation of dosing for each such cohort.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
This is a multiple dose study in which study participants may receive up to 42 days of dosing.  
In rare instances, it may be necessary for a participant to permanently discontinue
investigational product. Discontinuation of dosing does not necessarily represent withdrawal 
from the study (see Section 7.2). If investigational product is permanently discontinued, the 
participant may remain in the study to be evaluated for the remainder of the study. At a 
minimum, an early termination visit will be conducted. See the Schedule of Activities for 
data to be collected at the time of intervention discontinuation (early termination) and 
follow-up and for any further evaluations that need to be completed.  Additional follow-up 
may be required for safety evaluation, at the discretion of the investigator. 
ECG Changes 
A participant who meets either bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from the study. 
•
QTcF >500 msec.
•
Change from baseline: QTcF >60 msec.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE.
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed.
Adverse Events
Treatment will be discontinued and the participant withdrawn from the study for:
•
Treatment-related serious adverse events (SAEs);
•
Other serious or severe AEs, at the discretion of the investigator or sponsor.
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Laboratory Abnormalities
All of the following laboratory abnormalities require discontinuation if they are confirmed:
•
Hyperglycemia: see Section 6.5.5;
•
Creatine kinase >10 x ULN;
Note: Urine myoglobulin and serum creatinine (SCr) will be performed as reflex 
testing for any participant with creatine kinase >10 x ULN.
•
AST or ALT that meets ANY of the following:
•
>3 x ULN with at least one total bilirubin value >2 x ULN;
•
>3 x ULN accompanied by signs or symptoms consistent with hepatic injury
[eg, new onset elevated prothrombin time/international normalized ratio 
(PT/INR)];
•
Two sequential AST or ALT elevations >5 x ULN, regardless of total bilirubin or 
accompanying signs or symptoms.
NOTE: See also Appendix 6 for potential cases of drug-induced liver injury.  
Potential Cases of Acute Kidney Injury
Abnormal values in serum creatinine (SCr) concurrent with presence or absence of increase 
in blood urea nitrogen (BUN) that meet the criteria below, in the absence of other causes of
kidney injury, are considered potential cases of acute kidney injury and should be considered 
important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 μmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically
feasible, preferably within 48 hours from awareness.
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 μmol/L] in SCr
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 μmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury.
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result.  This evaluation should include laboratory tests, detailed history, and physical 
assessment.  In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
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examination, and urinary indices.  All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr.  If ≥2 healthy participants at a given dose level are noted to have 
2 consecutive SCr results of ≥0.3 mg/dL (or ≥26.5 μmol/L), an assessment of whether the 
finding may be considered an adverse drug reaction should be undertaken.
Prohibited Medications
Participants who are treated with any prohibited medication during the course of the study 
may require discontinuation.  Participants who are administered or take a prohibited 
medication should be discussed with the sponsor for possible withdrawal from the study.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should
be conducted. See the Schedule of Activities for assessments to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be 
completed. 
The early discontinuation visit applies only to participants who are randomized and then are 
prematurely withdrawn from the study.  Participants should be questioned regarding their 
reason for withdrawal.  
The participant will be permanently discontinued both from the study intervention and from
the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining
samples, but data already generated from the samples will continue to be available, and may 
be used to protect the integrity of existing analyses. The investigator must document any 
such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.  When a participant withdraws from the study 
because of an SAE, the SAE must be recorded on the CRF and reported on the Clinical Trial 
(CT) SAE Report.
Lack of completion of all or any of the withdrawal/early termination procedures will not be
viewed as protocol deviations so long as the participant’s safety was preserved.
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Withdrawal of Consent: 
Participants who request to discontinue receipt of study treatment will remain in the study
and must continue to be followed for protocol-specified follow-up procedures.  The only
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of investigational product or also from study
procedures and/or posttreatment study follow-up, and entered on the appropriate CRF page. 
In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
•
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;
•
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented
in the participant’s medical record;
•
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
Participants will be screened within 28 days prior to administration of the investigational 
product to confirm that they meet the study population criteria for the study.  The investigator 
(or an appropriate delegate at the investigator site) must obtain a signed and dated ICD
before performing any study-specific procedures.  If the time between screening and
dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug shipment), then 
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p artici pa nts d o n ot re q uire rescreeni n g if t h e la b orat or y res ults o btai ne d pri or t o first d o se
ad mi nis trati o n me et eligi bilit y criteria.
A par tici pa nt w h o q ualifi ed f o r this p r ot oc ol b ut di d n ot e nr oll fr o m a n earlier co h ort / gr o u p
ma y  be use d i n a s u bse q ue nt co h ort / gro u p wit h o ut rescree ni ng, p r o vi de d la b orat or y res ults 
o btai ne d pri o r t o t he first d ose a d ministrati o n m eet eli gi bilit y criteria f or t his st u d y. 
 
 
St u d y  pr oce d ures a n d t heir ti mi n g are su m ma riz e d in t he S c he d ule of A cti vities. Pr ot oc ol
w ai vers or e xem pti o ns are n ot all o we d.
I m media t e saf et y c oncer ns s h o ul d be disc usse d wi t h t he s p o nsor i m me dia tel y u p o n
occ u rre nce or a ware ness t o determ i ne if the p artici pa nt s h o ul d c o nti n ue or dis c o ntin ue st u d y  
i nterve nti o n.
A d here n ce t o th e st u d y desi g n r e q uire me nts, incl u di n g t h ose s pec ified i n t he S c he d ule of 
A cti vities, is esse ntial a n d re q ui re d for st u d y  c o nd u ct.
All scree ni ng e val uati o ns m ust be c o m plet e d a nd re vie w e d t o c o nfir m t hat pote nt ial 
parti ci pa nts meet all eli gi bilit y criteria. T he i n ve sti gat or will mai nt ai n a scree ni n g l og t o 
rec or d details of all part icipa nts scree ne d a n d t o c o nf ir m eli gi bilit y o r recor d reas o ns for 
scree ni n g fail ure, as a p plica ble.
E ver y eff ort s h o ul d be ma de t o e ns ure t hat p rot oc ol -re q uire d tests a n d pr oced ur es are 
c o mplete d as descri be d.  H o we ver , it is a ntici pate d t hat fro m t ime t o time t he re ma y be 
circ u msta n ces o utsi d e t he co n tr ol of th e i nve sti gat or t hat ma y ma ke it u nfeasi ble t o perfor m 
t he test.  In t hese cases, t he i n v esti gat or must ta ke all ste ps necessar y t o ens ure t he safet y a n d 
w ell-bei n g of t he partici pa nt.  W he n a p r ot oco l-re q uire d test ca n n ot be perf orm e d, the 
i nve sti gat or wi ll d oc ume nt t he reas o n f or t he misse d test a n d a ny c orrecti ve an d pre ve n tive 
acti o ns t hat he or she has ta ke n t o e ns ure t hat re quir e d pr oce sses are a dh e re d t o as s o o n as
p ossi ble.  T he st u d y te am m us t be i nf or me d of t hese i nci de nts in a t i mel y m a nner .
Al l eff orts wi ll be ma de t o c o n d uct pr oc e d ures at t he exact n o mi nal ti me relat i ve t o d osi n g.  
Pr oc e d ures 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 c o nd u cte d wit hi n 
1 0 % of t he n o mi nal time (eg, wit hi n 6 mi n ut es of a 6 0- mi n ute sam ple) relati ve t o d osi n g will 
n ot be ca pt ure d a s a pr ot oc ol deviati o n, as l o n g as t he e xact ti me of t he pr oce d u re is n ote d o n 
t he s o urce d oc ume n t a n d data c ollectio n t o o l (e g, C R F / DC T ).  Pr oce d ures sche d ule d m o re 
tha n 1 0 h o urs after d ose a d mi nistrati o n t hat are c o nd u cte d ≤1 h o ur a wa y  fr om 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 o t oc ol de viati o n, as l o n g as t he e xact ti me
of t he pr oce d ure is n ote d o n t he s o urce d oc u me nt a n d data c ollecti o n t o ol (e g, C R F/D C T ). 
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When multiple procedures are scheduled at the same time point(s) relative to dosing, the 
following chronology of events should be adhered to, where possible:
•
ECGs: obtain prior to vital sign measurements and as close as possible to the
scheduled time, but prior to blood specimen collection (refer to Section 8.2.3);
•
Vital Signs (BP and pulse rate): obtain as close as possible to the scheduled time, but
prior to blood specimen collection (refer to Section 8.2.2);
•
Weight: obtain as close as possible to the scheduled time, but prior to eating and 
drinking and prior to dose administration, where applicable (refer to Section 8.6.3);
•
Fasting blood samples: after assessment of 12-lead ECG and vital signs but prior to
dosing;
•
PK blood specimens: obtain at the scheduled time (for 0H samples, collect before 
dosing and as close as possible to dosing time, where applicable);
•
Dosing: must occur at the scheduled nominal time and following predose blood 
sample collection;
•
Breakfast: provided for consumption following dosing, where applicable (see 
Section 5.3.1).
Note that if an IV catheter is placed for serial blood sample collections, ECGs and vital signs
(pulse rate, BP) assessments should be either collected prior to the insertion of the catheter or 
sufficient rest period after catheter insertion introduced to minimize impact of catheter 
placement on these assessments.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in Part A of this study is
approximately 535 mL.
The total blood sampling volume for individual participants in Part B of this study is 
approximately 420 mL. 
The total blood sampling volume for individual participants in Part C of this study is 
approximately 525 mL.
The actual collection times of blood sampling may change.  Additional blood samples may 
be taken for safety assessments at times specified by Pfizer, provided the total volume taken 
during the study does not exceed 550 mL during any period of 60 consecutive days.
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To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1. Efficacy Assessments
Not applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities.
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety concerns.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, 
throat/mouth, neck, skin, cardiovascular, respiratory, gastrointestinal, lymphatic,
musculoskeletal, and neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms.
Physical examinations may be conducted by a physician, trained physician's assistant, or
nurse practitioner as acceptable according to local regulation. 
8.2.2. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of supine rest. The same arm 
(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements.  
When triplicate measurements are required (see Schedule of Activities), they will be obtained 
approximately 3 minutes (±1 minute) apart; the average of the triplicate measurements on 
Day -1 will serve as each participant’s time-controlled baseline value. The same properly 
sized and calibrated BP cuff will be used to measure BP each time.  The use of an automated
device for measuring BP and pulse rate is acceptable; however, when done manually, pulse 
rate will be measured in the brachial/radial artery for at least 30 seconds.  When the timing of 
these measurements coincides with a blood collection, BP and pulse rate should be obtained 
prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
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8.2.3. Electrocardiograms
Standard twelve (12)-Lead ECGs should be collected at times specified in the Schedule of
Activities section of this protocol using an ECG machine that automatically calculates the
heart rate and measures PR, QT, and QTc intervals and QRS complex. All scheduled ECGs 
should be performed after the participant has rested quietly for at least 10 minutes in a supine
position. When a meal or snack is scheduled at the same time as an ECG, the ECG 
measurement must be performed prior to the meal/snack.
Triplicate 12-lead ECGs will be obtained approximately 3 minutes (±1 minute) apart; the 
average of the triplicate ECG measurements collected at each nominal time point on Day -1 
will serve as each participant’s time-controlled baseline value. To ensure safety of the 
participants, a qualified individual at the investigator site will make comparisons to baseline 
measurements. Additional ECG monitoring will occur if a) the mean value from the 
triplicate measurements for any postdose QTcF interval is increased by ≥30 msec from the 
baseline and is >450 msec; or b) an absolute QTcF value is ≥500 msec for any scheduled 
ECG. If either of these conditions occurs, then a single ECG measurement must be repeated 
at least hourly until QTcF values from 2 successive ECGs fall below the threshold value that 
triggered the repeat measurement.
If a postdose QTcF interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTcF value is ≥500 msec for any scheduled ECG for greater than 4 hours (or 
sooner, at the discretion of the investigator), or QTcF intervals get progressively longer, the 
participant should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTcF intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).
ECG data will be submitted to a blinded central reader for assessment.  The final ECG report 
from the central reader should be maintained in the participant’s source documentation and 
be the final interpretation of the ECG recording. 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read 
QTcF value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the 
Schedule of Activities for the timing and frequency.
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The investigator must review the laboratory report, document this review, and record any
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 3 days after the last dose of study intervention should be
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by
the investigator, the etiology should be identified and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted 
in accordance with the laboratory manual and the Schedule of Activities.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
Participants may undergo random urine drug testing at the discretion of the investigator.  
Drug testing conducted prior to dosing must be negative for participants to receive 
investigational product (exception may be made for medically prescribed benzodiazepines, 
see Section 5.2).
8.2.4.1. Fasting Fingerstick Blood Glucose (via Glucometer)
Investigators will monitor fasting fingerstick blood glucose (FSBG) using a glucometer at the
times specified in the Schedule of Activities. While the participant is confined to the CRU,
FSBG measurements should be taken each morning before breakfast.
FSBG readings will be maintained at the sites in source documents, and only the glucose
results from the laboratory will be reported in the study database. The sites may share the
FSBG readings with the sponsor for the purpose of dose-escalation decisions, but these data
will be stored in the sites’ source documents unless related to an AE as described in 
Section 8.2.4.2 below. 
If an FSBG result is ≤70 mg/dL, a second FSBG should be obtained to confirm the glucose 
value, in addition to a venous sample that will be sent to the clinical laboratory for 
confirmation. If the value from this second FSBG is also ≤70 mg/dL, the second value will 
be recorded as a hypoglycemic AE (see Section 8.2.4.2). FSBG will continue to be 
monitored until the glucose value returns to >70 mg/dL. Samples may be taken more 
frequently if deemed necessary by the investigator. FSBG readings from a glucometer are 
permitted at any time if the investigator or participant notes symptoms of hypoglycemia.
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8.2.4.2. Hypoglycemia Reporting
Hypoglycemia will be assessed and reported in several categories: severe hypoglycemia,
documented symptomatic hypoglycemia, asymptomatic hypoglycemia, and probable
hypoglycemia.
Severe hypoglycemia: In order to be considered severe hypoglycemia all of the following
3 criteria must be met:
1. The participant had 1 of the following:
•
Blood glucose <50 mg/dL; or
•
If blood glucose was not measured, the clinical manifestations were reversed by
carbohydrate administration.
2. The participant required the assistance of another person to actively administer
carbohydrate, glucagon, or other resuscitative actions.
3. The participant exhibited at least 1 of the following neurological symptoms:
•
Memory loss;
•
Uncontrollable behavior;
•
Irrational behavior;
•
Unusual difficulty in awakening;
•
Suspected seizure;
•
Seizure;
•
Loss of consciousness.
Documented symptomatic hypoglycemia: An event during which typical symptoms of
hypoglycemia are accompanied by a measured glucose concentration ≤70 mg/dL.
Asymptomatic hypoglycemia: An event not accompanied by typical symptoms of
hypoglycemia but with a measured glucose concentration ≤70 mg/dL.
Probable symptomatic hypoglycemia: An event, during which typical symptoms of
hypoglycemia are not accompanied by a real time glucose determination, but were
presumably caused by a plasma glucose concentration ≤70 mg/dL. The clinical picture must
include prompt resolution with oral carbohydrates, subcutaneous glucagon, or intravenous
glucose.
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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or that caused the participant to discontinue the
study intervention (see Section 7).
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent,
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving investigational product), through and including 
a minimum of 28 calendar days after the last administration of the investigational product.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the case report form (CRF), not the AE section.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and
Pfizer concurs with that assessment.
Investigators are not obligated to actively seek AE or SAE after conclusion of the study
participation. However, if the investigator learns of any SAE, including a death, at any time
after a participant has been discharged from the study, and he/she considers the event to be
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form immediately and under no circumstance should this 
exceed 24 hours, as indicated in Appendix 3. The investigator will submit any updated SAE 
data to the sponsor within 24 hours of it being available.
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SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
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An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the investigator’s brochure and will notify the IRB/EC, if 
appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female partners of male participants will be collected after the 
start of study intervention and until the last follow-up visit.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a participant enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.3.6. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 6 6
E x p os ures t o t he i n vestiga tio nal p r o d uct u n der st u d y ma y occ ur i n cli nical trial setti n gs, s uc h 
as me dicati o n er r ors.
S af et y E ve n t
Rec or d e d o n t he CR F  
Re p orte d o n t he CT S A E Re p ort 
F or m t o Pfizer S a fety Wit hi n 2 4 
H o urs of A w are ness
Me di cati o n err ors 
A ll (re gar dless of w het h er 
assoc iate 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 erro rs i ncl u de:

Me d icati o n err ors i n v olvi n g par ticipa nt e x p os u re t o t he in vest i gati o nal pr o d uct;

P ote ntial m e dicati on er r 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 
o r d o n ot i n v olve t he st u dy partici pa nt .
S uc h me dicati o n err ors occ urri n g t o a st u d y p artici pa nt are t o be ca p t ure d o n t he m edica ti o n
err or pa ge of t he C R F, w hic h is a s pecific versio 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 o r sh o ul d be n oti fie d i m me diatel y.
W he t her or n ot t he me dicati o n err or is acco m pa nie d b y  an A E, as deter m i ne d b y t he 
in ve sti gat or, the m e dica ti o n err or is rec or de d o n th e me dicati o n error pa ge o f t he C R F a n d, if 
a p plica bl e, a n y ass ociate d A E(s), seri o us a n d n o nser i ous , are rec or de d o n an A E pa ge of t he 
C R F.
Me d icati o n err ors sh o ul d be re p ort e d t o P fizer Safet y wit hi n 2 4 h o urs o n a C T S A E Re p o rt 
F or m o nl y w he n ass oci a ted w it h a n S A E.
8. 4. Tr e at ment o f 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 t hat pr ojecte d t o res ult i n ex p os ures
greater t ha n t he defi ne d P K st o p pi n g l i mit 
 
wi t hi n a 2 4-h o ur ti m e 
peri o d will be c o nsi dere d a n o ver d ose .
I n t he eve nt of a n o ver d os e, t he i n vesti gat or/treati n g p hys icia n s h o ul d:
1.
C o ntact t he m e dical m o ni t or i mm e diatel y.
2.
C l osel y m o nit or t he partici pa nt f or a n y A Es/ S A Es a n d lab orat or y  a b n or malities u ntil
P F - 0 7 0 8 1 5 3 2 ca n n o l o n ger be detected s ys te micall y (at least 5 d a y s).
3.
D oc u me nt t he q u a ntit y of t he e xcess d ose as w e ll as t he d uratio n of t he o ve r d ose i n 
the C R F .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 6 7
4.
O v er d ose is re por ta ble t o Safet y o nl y w he n as s oci ate d wit h an S A E.
5.
O btai n a bl o o d sam pl e f or P K a nal ys is wit hin 3 da ys fr o m t he date of t he last d ose of 
st u d y i nter ve nti on if re q ueste d b y t he m edical m o nit o r ( deter mi ned o n a case-b y -case 
basis).
D ecisi ons re gar din g d o se i nterr u pti o ns or m o dific atio n s will be ma de b y th e i n vesti g at or i n 
co ns ultati o n wit h the m e dical m onit or base d o n t he cli nical e val uati o n of t he partici pa nt.
8. 5. P h ar m a c o ki netics
8. 5. 1. P l asm a f or A n a l ysis of P F- 0 7 0 8 1 5 3 2
Bl o o d sa m ples of a p pro xi mat el y 3 m L , to pr o vi de a p pr o xi matel y 1 m L of pl asma , will be
c ollected i nt o a p p r o priately la bele d t u bes c o ntai ni n g d i p otassi u m et h yle ne dia mi netetraacetic 
aci d ( K2E D T A ) f or meas ure me nt o f plas ma c o nce ntrati o ns o f P F -0 7 0 8 1 5 3 2 at ti mes
s pecifie d i n t he S c he d ul e of A cti vities. I nstructi o ns f o r t he c ollecti o n a n d ha n dl i n g of 
bi o lo gi cal sa m ples will be pr o vi de d i n t he la borat or y ma n ua l or by t he s p o ns or. T he act ual 
da te an d ti me ( 2 4- h o ur cl oc k ti m e) of eac h sa m p le will be re c ord e d.
T he act ual ti mes ma y  c h a n ge, b ut t he n u m ber of sa m ples will re mai n t he sa me. A n y  c ha n ges
i n t he tim i n g or a d di ti o n of ti me p oi nts f or a n y pla n ne d st ud y  assess me nts m ust be 
d oc u m e nte d a n d a ppr o v e d b y t he rele va nt st u d y tea m me m ber a n d the n ar c hi ve d i n the 
s p o ns or a n d site st u d y files b ut will n ot c o nst it ute a pr ot oc ol a me n d me nt.
S a m ples will be use d t o eval uate t he P K of P F -0 7 0 8 1 5 3 2. Sa m ples c ollecte d f or 
meas ure me nt of plas ma c o nce ntrati o ns of P F- 0 7 0 8 1 5 3 2 will be a nal yz e d usi n g a vali d ate d
a nal yt ical met h o d i n c o m plia nce wit h a pplica ble sta n dar d o perat i n g pr oce d ures (S O Ps).
 
 
 
 
 
 
T he P K sa m p les 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 ovi de d t o 
t he in vesti gat or site t o m ai ntai n sa m ple inte grit y. A n y  de viati o ns fr o m t he P K sa m ple 
ha n dl i n g pr oce d ure (e g, sa mple c ollecti o n a n d pr o cessi ng s te ps, i nteri m st ora ge or s hi p pi ng
c o n diti o ns), incl 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 r e por ted t o t he sp o ns or.  
O n a case -b y -case basis, t h e s po ns o r ma y deci de as t o w het her sa m ple i nte grit y has bee n 
c o m pr o m ise d.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 6 8
Dr u g c o nce ntrati o n i n f or mati o n t hat ma y u n bli n d t he st u d y  will n ot be re p orte d t o 
i n vesti gator sites or bli n de d pers o n nel u nt il t he stu d y has bee n u n bli n de d .
 
 
 
 
8. 5. 3. U ri ne f or A n al ysis of P F- 0 7 0 8 1 5 3 2
U ri ne will be c ollecte d at times s pecifie d i n t he Sc he d ule o f A cti vities.

Pri or t o d o si ng o n D ay 1 , eac h partici pa nt m ust c o m plete a f o rce d v oi d wit h an
ali q u ot (a p pr o xi matel y 1 0 m L ) fr o m thi s uri ne ( uri ne bla n k) la bel e d an d st ore d
fr oze n f or meas ure me nt of dr u g c o nce ntrati o ns, per detaile d i nstr ucti o ns offe re d i n a 
la b orator y ma n u al pri or t o t he start of t he st u dy. 

F oll o wi n g d osi n g o n D a ys  S pecifie d i n t he Sc he d ule of A cti vities, ea c h voi d p os t 
d ose will be c ollecte d an d sav e d i n a c o ntai ner a n d store d i n re fri gerat ed c o n dit i o ns
(ie, 2- 8° C) f o r t he d u rati on of t he c ollecti o n i nter val s, as s pecifie d i n t he S c he d ule of 
A cti vities.

J ust pri or t o t he first c ollecti o n i nter val, partici pa nts will c o m plete a f orce d v oi d 
a n d t he uri ne will b e disc ar de d;

At t he e nd of eac h c ollecti o n inter val, partic ipa nt s m ust c o m plete a f orced v oi d 
wi t h this c o m pl ete v oi d i ncl u de d as part of t he i nter val c ollecti on;

T he ur i ne c o ntai ner will be mi xe d t h or o u g hl y  a n d t otal v ol u me pl us wei g ht of t he 
uri ne c ollecte d d uri n g t h e in ter val rec or ded;

A n ali q u o t (a p pr o xi matel y 2 0 m L ) will be la be le d an d st ore d froze n f or t he 
p ote ntial me as ure me nt of dr u g co nce ntrati o ns
per detaile d i nstr ucti o ns offere d i n a la b orat or y ma n ual pri or t o t he start
of t he st ud y ; a n d t he remai ni n g uri ne discar de d. 
De tails re gar di n g t he pr o cessi n g, st ora ge a n d s hi p pi n g of t he sa m ples will be pr o vi de d i n t he
la b m a nual. T he s hi p me nt a d dress a n d assa y la b c o ntact i nf or mati o n will b e 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 uri ne sa m p les must be pr ocess e d as
i nd icate d to ma i ntai n sam ple i nte gri t y. A n y d e viati o ns fr o m t he uri ne sa m ple p r ocessi n g 
ste ps give n i n t he pr ot oc ol or la b ma n ual, i ncl u di n g a ny acti o ns ta ke n, m ust be d oc u me nte d 
a n d re po rte d to t he s p o ns or. O n a case-b y -case ba sis, th e s p o ns or ma y ma ke a d eter mi nati o n
as t o w het her sa m ple i nte grity has b een c o m pr o mise d. A n y s a mp le deeme d o utsi de o f 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 6 9
esta blis he d sta bilit y, or of q uesti o na ble i nte g rity, will be c o nsi dere d a pr ot oc ol d evia ti on.  
Sa m ples f or a nal ys is of P F - 0 7 0 8 1 5 3 2 PK wil l be a nal y ze d usi n g va li date d a nal y tical meth o ds
i n c o m plia nce with Pfi zer sta n dar d o perati n g pr oced ures .
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 0
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
8. 6. 3. B o d y Wei g ht
B o d y  weig h t meas ure me nts will b e o btai ne d at t he ti me p o i nts o utli ne d i n t he S c he d ule of 
A cti vities.  If p ossi ble, t h e sa me scale s h o ul d be use d f or a p a rtic ular partici pa nt f or all b o d y  
we i g ht me as urem e nts o btai n e d at t he C R U. F or meas uri n g wei g ht, a scale wit h a p p r o priate 
ra n ge a n d res ol uti o n is use d a n d m u st be placed o n a stabl e, flat s urface. 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 1
B o d y wei g h t will be m eas ure d at o ut patie nt visits t o the st ud y  site as liste d i n t he S c he d ule of 
A ctivities u n de r t he f oll o win g c o n diti o ns:

After v oi d of uri ne ;

After r e m o val of s hoes, b u l ky l a yers of cl ot hi n g, an d jac kets so t hat o nl y  li gh t 
clot hi n g re mai ns; 

W h ile re mai ni n g still duri n g meas ur e me nt.
D uri n g a d mi ssi o n t o t he C R U, b od y  wei ght will be me as ure d at t he time p oi nt s liste d i n t he 
S c he d ule of A cti vities. Meas ure m e nt will be ta ke n u n der t he f oll o wi n g c o n ditio ns:

I n t he m or ni n g, p ri or to eati n g a n d d rin ki n g a n d pri or t o d ose a d mi n istrati o n, w here 
a pp lica ble;

A fter the par tici pant has bee n as ke d t o v o i d;

W hile we ari ng o nl y a h os p ital g ow n a n d n o s h oe s;

W h ile re maini n g still duri n g m eas ure me nt. 
 
 
  
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 2
  
 
 
 
 
  
 
 
 
 
 
 
8. 9. He a lt h Ec o n o mics
H ealth e c o n o mics/ me dic al res o urce u tilizati o n a n d h ealt h ec o no mi cs pa ra meters are n ot
e val uate d i n t his stu d y .
9. S T A TI S TI C A L C O N SI D E R A TI O N S
De taile d met h o d ol og y f or s u mmar y a n d statistical a nal ys 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 statistical a nal ysis pla n ( S A P), w hic h wil l be
m ai ntai ne d b y  t he sp 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 o t oc ol w here 
a p pro p riate; h o we v er, a n y maj or m o dificatio ns of t he pri mar y  e n d p oi nt defi niti o ns o r t heir 
a nal ys es will als o be ref lecte d i n a pr ot oc ol a me n dme nt.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 3
9. 1. St a tistic al H y p ot hes es
N o f o r mal statistical h y p ot hesis testi n g will b e per for me d i n t his stu d y .
9. 2. S a m ple Size Det er mi n ati o n
P ar t A a n d P a rt C (if co n d u cte d), partici pa nts wit h T 2 D M : a sa m ple size of u p t o 
a p pr o xi matel y 1 0 partici pa nt s p er co h ort (8 ac tive, 2 p lace b o) h a s bee n selecte d t o mi ni mize 
e x p os ure t o h u ma ns t o a ne w c he mical e ntit y w hile all o wi n g a de q uate c haracteriz ati o n of
safety a nd t olera bili t y, P K,
 at eac h d ose le vel i n t his p o p ulati o n.  
P a rt B (if c o n d ucte d), o bese pa rtici pa nts: a sa m ple size of u p t o ap p r ox i matel y
1 5 partici pa nt s p er c o h ort ( 1 2 acti ve, 3 p laceb o) has bee n s el ected t o m i ni mize e x p o s ure of
h u ma n s t o a new c he mical e ntit y w h ile all o wi n g a de q ua te c haracterizati o n of safety a n d 
t olera bilit y, P K ,
 at eac h d ose le vel i n t his p o p ulati o n. 
 
9. 3. P o p ul at i o ns f or An al ysis
F or p ur p ose s of a nal yses th e f oll o wi n g p o p ul atio ns are de fi ne d:
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 4
T a ble 1 0.
P o p ul ati o ns f or A n al y sis
P o p ul a tio n
Descri pti o n
E n r olled 
All part ici pa nts w h o sig n t he IC D .
Ra n d o m l y assi g ned t o 
i n vestigat io nal pr o d uc t
All p artici pa nts ra nd o ml y  assig ne d t o i n ve sti ga ti o nal pro d uct re gar dless of
w het her or n ot t he i n ves ti gati o nal pr od uct wa s a d mi nistered .
E val ua ble
A ll partic i pa nts ran d o m ly assi g ne d to i n vesti gati on al pr o d u ct a n d w h o ta ke at 
least 1 d ose of in vesti gat i ona l pr od uc t. Partici p a nts will b e a nal yze d acc o rdi n g t o 
the pr o d uc t t he y actuall y recei ve d .
Safet y
A ll partici pa nts ra n d o ml y assi gne d t o in vesti gat i ona l pr o d u ct an d w h o ta k e at 
least 1 d ose o f i nves ti gati ona l pr o duct.   Partici p a nts will be a nal yze d accor di n g t o
t he pr o d uct t he y act ually recei ve d .
P K C o nce ntrat i o n Set 
The P K c o nc e ntrati o n p o p ulati o n is d efi ne d as all ra n d o mize d partici pa nts w h o 
receive d at least 1 d o se of P F -0 7 0 8 1 5 3 2 a n d i n w h o m  at least 1 pl as ma 
co n centrati o n v al ue is re p o rted .
P K Par a meter Set 
The P K para me ter p o p u lati on is defi ne d as all ra nd o m ized p artici pant s t hat 
recei ve d at least 1 d o se of P F-0 7 0 8 1 5 3 2 a n d ha ve at least 1 of t h e P K para m eters
o f inter est calc ulated.
 
 
9. 4. S t atistic al A n a lyses
9. 4. 1. Effic ac y A n a l yses
A n ef ficac y a nal ysis is n ot a p plica ble t o t his st u d y.
9. 4. 2. S afet y A n al yse s
A ll partici pa nt s w h o re ce i ved at leas t 1 dose of st u d y  me dic ati o n will be i ncl u de d i n t he 
safety a n al yses a n d listi n gs.  A Es, E C Gs, B P, p ulse rate, a nd s afet y l a b orato r y data will be 
re vie wed a n d s u m m arize d on a n o n g oi n g b asis d uri n g t he st u d y t o e valuate t he safety of 
partici pa nts. A n y cli n ical la b orat ory, E C G , BP, a n d p ul se rate a b n or malities of p otentia l 
cli nical c o ncer n will be d escri be d.  Safet y dat a wil l be pres ente d i n ta b ular a n d/ or gra p hic al 
f or mat an d s u m marize d descri pti vel y, w here a p pr o p riate.
M e dical hist ory a n d p h y sical e xa mi nat io n i nf or mati o n, as a pp lica ble, collecte d d ur i n g t he 
c o urse of t he st u d y will be c o nsi de re d so urce data a n d wi ll n ot be req u ire d to be re p ort e d, 
u nles s ot her wise not e d.  H o w e ver, a n y u n t o war d fi n din gs i de ntifie d o n p h ys ical a n d/ or 
ne ur ol o gica l ex a mi nati o ns c o nd ucte d d ur i n g t he acti ve c ollecti o n peri o d w ill be ca pt ured as
A Es, if t h ose fi n di n gs meet t he defi niti o n of a n A E. 
Dat a c ollecte d at scree ni n g t hat are use d for i ncl usi o n/e xcl usio n criteria, s uch as la b ora t or y 
data ( u nless n ote d bel o w), E C G s, a n d vita l si gns, wil l be co ns i 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 nl ess ot h er wise n ote d.  De m o g rap hic d ata c oll ecte d at screeni n g 
wi ll be re p or ted. I n a ddit i on , selecte d scree nin g lab orat or y  data:
 
 T B A
 will be re p orte d .
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 5
9. 4. 2. 1. E lectr oc ar dio gr a m A n al yses
C ha n ges fr o m bas eli ne f or t he EC G p ar ameters Q T i nter va l, heart rate, QTc F inte r val, PR
i nterval , a nd Q R S i nter val will be su m mari ze d b y tr eatme nt a n d time.
T he n u m ber ( %) of partici pa nts wit h ma xi m u m p o std ose Q Tc F val u es a n d maxi m u m
i ncreases fr o m baseli ne i n t he f oll owi n g cate g ories w ill be ta b ulate d b y treatme nt: 
S afet y Q Tc F A ssess me nt
Pr o l o ngati o n
M ild
M o derate
S evere
A b s ol ute val ue ( msec)
4 5 0 -4 8 0
4 8 0 -5 0 0
5 0 0
I ncrease fr o m ba seli ne 
i n Q Tc F ( msec) 
3 0 -6 0
6 0
I n a d diti o n, t he n u m ber of partici p a nts wit h c orrecte d a n d u nc o rrecte d Q T v al ues > 50 0 msec 
wi ll be s u m marize d.
At t he n o m i nal time p oi nts, t he mea n of t he tri plicate meas ure me nts wi ll be used t o re prese nt 
a si n gle o bserva tio n at t hat ti me p oi nt.  I f a n y of t he 3 i n di vi d ual E C G traci n gs has a Q Tc F 
va l ue > 5 0 0 msec, b ut t he mea n of t he tri plicates is n ot > 5 0 0 msec, t he d ata fr om t he 
p artici pa nt ’s in di vi d ual tra ci n g wil l be de scri be d i n a safety secti o n of t he stu d y  re p ort in
or der t o place t he > 5 0 0 msec val ue i n a p pr o pri ate cli nical c o nte xt.  H o w e ver, val ues fr o m 
i n di vi d ual traci ngs wit hi n t ri plicate mea s ure me nts t hat are > 5 0 0 m sec will n ot be i ncl ude d i n 
t he cate g orical a nal ysis u nless the a vera ge fr o m t he tri pli cate meas ure me nts is als o 
> 5 0 0 msec.
I n a d diti o n, a n atte m pt will be ma de t o e x pl ore a n d c haracterize t he relati o nshi p b et wee n 
plas ma c o nce n trati o n a n d Q T i nter val len gt h usi n g a P K 
 m o del i n g a p pr oac h.  T h e res ults
of s uc h a nal ys es will n ot be i ncl u de d i n t he C S R. 
9. 4. 3. P h a r m aco ki netic A n al yses
9. 4. 3. 1. P F -0 7 0 8 1 5 3 2 P h ar m ac o ki netics
T he p o p ulati o ns f or P K c o n ce ntrati o n a n d P K p ara meter a nal yses are defi ne d i n Ta ble 1 0 .
P K par a meters f or P F - 07 0 8 1 5 3 2 f oll o wi n g m ulti ple d ose a d ministrati o n will be deri ve d fr o m 
t he c o nce ntrati o n-ti me pr ofiles usi n g n o n-c o m part me ntal met h o ds as data per mit. T h e P K 
par amet ers t o be assess e d i n t his st u d y, t heir def i niti o n, an d met h o d of d eter mi nati o n are 
o utl i ne d i n Ta ble 1 1 an d T a ble 1 2 . I n all cases, act ual P K sa m pli n g t i mes will be use d i n t he 
deri vati o n of P K para meters. P K sa m ples fr o m pl a ce b o sa m ples will n ot be r o uti n el y 
a nal yz e d.
Ad diti o nal de tail o n P K para me ter d efi niti o n for titrated a n d n o n -titrated c o ho rts 
w ill be pr o vi de d i n t he S A P.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 6
T a ble 1 1.
Defi n itio n of Pl as m a P K P ar a m et ers f or P F -0 8 7 0 8 1 5 3 2
P a r a m eter
D a y 1 ( D 1) or 
Ste a d y S t ate
(S S )
Def initi o n
M e t h od of Deter m i n ati o n
C ma x
D 1 & S S  
M a xi m u m p las ma c o nce ntrat i o n 
o bser ve d fr o m ti me zer o t o 
2 4 h o ur s
O bser ve d directl y fr o m data
T ma x
D 1 & S S
T i me f or C ma x
O bser ve d directl y fr o m data as ti me of 
first occ urre nc e
C m a x ( d n)
D 1 & S S
C ma x n or m alized t o a 1 m g d ose
C ma x / D ose
A U C 2 4
D 1 & S S  
A rea u n der t he p lasma 
c o ncen trati o n-ti me pr ofile fr o m 
ti me zer o t o ti me 2 4 h o urs
Li near/ L o g tra pez oi dal met h o d
A U C 2 4 ( d n)
D 1 & S S
A U C 2 4 n or m alize d t o a 1 m g 
d ose
A U C 2 4/ D ose
 
 
 
 
 
 
 
t½ a
S S
T er m i nal hal f-life
L o g e( 2)/ kel, w here kel is the ter mi nal 
p hase rate co nsta nt c alc ulated b y a 
li near regr essi o n of t he l o g-li near 
c o ncentra ti o n-ti me c ur ve.  O nl y t h ose
da ta p oi nts j u dge d t o des cri be t he 
termi nal l o g -line ar decli ne wil l be 
use d i n t he re gressi o n.
a.
If data per mi t.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 7
T a ble 1 2.
Defi niti o n of Uri n e PK P ar a meters f o r P F- 0 8 7 0 8 1 5 3 2
P ar a m eter
Ste a d y 
St at e ( S S)
Defi niti o n
M e t h od o f Deter mi n ati o n
Ae 2 4
S S
A m o u nt of u nc ha n ge d dr u g
rec o vere d i n uri n e o ver 2 4 h o urs
S u m of [ uri ne c o nce ntrati o n * sa m ple 
v o l u me a] f or eac h c ollecti o n o ver t he 
d o si n g i nter val
Ae 2 4%
S S
Perce nt of d ose rec o vere d i n uri ne 
as u nc ha n ge d dr u g
1 0 0 * Ae 2 4/ D ose
C L r
S S
Re nal cl earance
Ae 2 4/ A U C2 4
a.
sa mple v ol u m e = ( Uri ne wei g ht in g /1. 0 2 0) , w h ere 1. 0 2 0 g/ m L is t he a p pr o xi mate s pecific gr a vit y of 
uri ne .
T h e plas m a a n d uri ne P K para meters will b e s u m mariz ed descri p ti vely b y act ual d ose
recei ve d (a n d treat ment, if a p plicable) , i n acc o r da nce wit h Pfizer sta n dar d s. Ea c h C o h ort
will be c o nsi dere d as a se parate treat me nt. If data per mit, d ose - nor malize d area un der t he 
plas ma c o ncentrati o n t ime p r ofile fr o m ti me 0 to 2 4 hr [ A U C 2 4 ( d n)] a n d d ose- n or malize d 
C ma x [ Cma x ( d n)] will be pl otte d a ga i nst d ose ( p ote ntiall y  o n a l o garit h mic scale de pe ndi n g o n 
the e xte n t of t h e dose ra n ge) (an d tr eatme n t, if a p plica ble), a n d wil l incl u de i n d i vi dual 
partic ipa nt val ues a n d t he ge o m etric mea ns f or each d ose (a n d treat me nt, if a p pli ca ble).
T h ese pl ots wil l be u se d t o hel p u n dersta n d t he relati o ns hi p bet wee n t he P K para meters a n d 
d ose (a nd treat ment, if ap pl ica ble).
Plas m a c on ce ntrati o ns of P F- 07 0 8 1 5 3 2 will be liste d a n d descri pti vel y s um marize d b y  
n o mi nal P K s a m pli n g ti me a n d d ose (a n d treat ment, if a p p lica ble). I n di vi d ual partici pa nt a nd
me dia n pr ofiles of t he plasma c o nce nt rati on-t i me d ata will be p l otte d b y  d ose (a n d treatme n t,
if ap plica ble ) usin g act ual an d n o mi nal ti mes, res pec ti vel y. M edia n pr o files will be 
prese nte d o n b ot h li near-lin ear a n d l o g-l i near scales.
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 7 9
 
 
 
 
 
9. 5. I nte ri m A n a l yses
A s t his is a s p o ns or-o pe n st u d y, t he s po ns or will c o n d uc t u n bli n de d re vie w s of t he data 
d uri n g t he c o urse of t he st u dy f o r t he p ur p ose of safet y assess me nt a n d facilitati n g
d ose- escalati o n decisi o ns.  I n ad diti o n, t hese re vie ws ma y  facilitate PK  
m o del in g a n d/ or 
s u p porti n g cli nical de vel o p me n t.
9. 5. 1. D at a M o nit or i ng C o m m ittee
T his stu d y wi ll n ot use a dat a mo nit o ri n g c o m mittee (D M C ).
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI

PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 80
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
•
Consensus ethical principles derived from international guidelines including the
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;
•
Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, investigator’s brochure (IB), and other relevant
documents (eg, advertisements) must be reviewed and approved by the sponsor and 
submitted to an IRB/EC by the investigator and reviewed and approved by the IRB/EC
before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:
•
Providing written summaries of the status of the study to the IRB/EC annually or
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;
•
Providing oversight of the conduct of the study at the site and adherence to
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

PF-07081532
Protocol C3991002
Final Protocol, 16 January 2020
PFIZER CONFIDENTIAL
Page 81
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study.
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.
090177e1995f4769\0.1\Draft\Versioned On:16-Feb-2022 06:37 (GMT)

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 8 2
 
 
 
 
1 0. 1. 3. D at a Pr otect i o n
All parties will c o m pl y w it h all a ppl icable la ws, i nclu di n g la ws re gar din g t h e im ple me nta ti o n 
of or ga nizati o nal a n d tec h nical meas ur es t o e nsu re prote cti o n of p artici pant d ata.
Pa rtici pa nts’ pers o n al d ata will be st ore d at t he st u d y site i n e ncr ypte d e lectr o nic a n d/ or pa per
f orm a nd wi ll be p ass w or d p r otected or s ec ure d i n a l oc ke d r oo m t o e nsu re t hat o nl y  
a ut h orize d st u d y staff ha ve access.  Th e stu d y  site will i m ple me nt a p pr o priate tec h nical a n d 
o r 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 h e e ven t of
d isaster.  I n the e ve nt of a p ote ntial pe rs o nal d a ta breac h, t he stu d y  site s hall be resp o n sible 
f or deter mi ni n g w he ther a per s o nal data breac h has i n fact occu rre d a nd, 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 h e ri g hts a n d free do ms of nat ur al pers on s wit h re gar d to t he proce ssi n g of 
pe rs o nal data, partici pa nts w ill be assi g ned a si n gl e, partici pa nt-s pecific n u m erical co d e. 
A n y  partici pa nt reco r ds or data sets t hat are tra nsferre d t o t he s p o ns o r will c o ntai n t he
n u m erical c od e; p artici pa nt na mes wil l n ot b e tra nsferred. A ll ot her i de nt ifia ble data 
tra nsferre d t o t he s p o ns or will be i dentif ie d b y t his sin gl e, pa rtici pa nt-s pecific c od e. T he
st ud y site will mai ntai n a c o nfi de ntial list of partic ipa nt s w h o partici pate d i n th e stu d y,
lin ki n g eac h partic ipa nt ’s n u meric al co de to h is or her act ual i de ntit y. I n case of da ta
tra nsfer, t he s p on s or w ill p r otect the co nfi de ntiali t y of parti cip a nts’ pers on al data c o nsiste nt 
wit h t he cli nical st u d y agree me n t a n d a p plica ble pri vac y la w s.
1 0. 1. 4. D issemi n a ti o n of Cli nic al St u d y D at a
Pfi z er f ulfills its c o m mitme nt t o p u blicl y  discl ose cli nical st u d y res ults th r o u gh p o sti n g t he
result s of st u dies o n w w w.c lin icaltrials. g o v ( Clinica l Trials. g o v), t he E ur o pea n Cli nical Trials 
Data base ( E u d ra C T), a n d/o r w w w. pfizer.c o m, a n d ot her p u bli c re gistries i n acc or dance wit h
ap plica ble l ocal la ws/re g ula ti o ns.  In a d d iti o n, Pfizer re p orts stu d y result s o utsi de of t he 
re q uireme nts o f l ocal la ws/re gulati o ns p urs u a nt t o its sta n dar d o pera ti n g p r oce d ures (S O Ps).
I n all cases, st ud y  res ults are rep ort e d b y  Pfizer in a n o bje cti ve, accurate, bala nce d, a n d 
c o m plete man ner a n d are re p orte d r egar dl ess of t he o ut c o me of t h e st u d y or t he c o u ntr y i n
w hic h t he s t u d y was c o n du cte d.
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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods. Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.
Policy 0070 applies to new marketing authorization applications submitted via the
centralized procedure since 01 January 2015 and applications for line extensions and for new 
indications submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes
of “bona-fide scientific research” that contribute to the scientific understanding of the
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
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Data requests are considered from qualified researchers with the appropriate competencies to
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals
requesting access for commercial/competitive or legal purposes.
10.1.5. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion. It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring),
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during
the retention period without the written approval of the sponsor. No records may be
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
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When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.6. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from
source documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the investigator site file.
10.1.7. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
•
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;
•
Inadequate recruitment of participants by the investigator;
•
Discontinuation of further study intervention development.
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Study termination is also provided for in the clinical study agreement.  If there is any conflict
between the contract and this protocol, the contract will control as to termination rights.
10.1.8. Publication Policy
The results of this study may be published or presented at scientific meetings by the
investigator after publication of the overall study results or 1 year after end of the study (or
study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor
30 days before submission. This allows the sponsor to protect proprietary information and to
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in
this section will not apply.
10.1.9. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study team on demand (SToD) 
system.  
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card
contains, at a minimum, protocol and investigational product identifiers, participant numbers,
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
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staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for
advice on medical questions or problems that may arise during the study.  For sites other than
a Pfizer CRU, the contact number is not intended for use by the participant directly, and if a 
participant calls that number, he or she will be directed back to the investigator site.
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P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 8 8
1 0. 2. A p pe n d i x 2: Cli ni c al L a b or at or y Te sts
T h e foll o wi n g safety la b orat o r y tests wi ll be perf or me d a t times d efi ned i n t he S c he d ule of
A cti vities.  A d diti o nal la b orat or y re sults m a y be r e p orte d o n t hese sa m ples as a result of t he 
met h o d of a n al ys is o r t he t yp e of a nal yz er use d b y  t he cli nical lab orat or y ; or as deri ve d fr o m 
calc ulated val u es.  T hese a d diti o nal tests w o ul d n ot re q uire a dd iti onal c ollecti o n of bl o o d .  
U nsc he d ul ed cl i nical lab or at ory m eas ure me nts m a y  be obta i ned a t a n y ti me d uri n g the s t ud y  
t o assess a n y p ercei ve d safet y c oncer ns .
In ves tigat ors m ust d oc u me nt t heir re vie w of eac h la b orator y  safet y re p ort.
T a b le 1 4.
Pr ot oc ol -Re q u ire d S afet y La b or at or y Asse ss me nts
H e m at ol o g y
C h e mistr y / Ot her
Ur in al ys is
At s pec ified ti mes 
H e m o g l obi n
He mat ocri t
R B C c o u n t
M C V
M C H
M C H C
P latelet co u nt
W B C c o u nt
T otal ne ut r op hil s ( A bs)
E osi n o p hi ls ( A bs)
M o n oc y tes (A bs)
Bas o p h ils ( Abs)
L y m p h o c ytes ( A bs)
B U N/ U rea 
Ser u m C reati ni nea
Pl as m a Gl uc ose (f astin g)
Ca lci u m
S o d i um
P ota ssiu m
C hl o ri de
T o tal C O2 ( bicar b o nate)
A S T
A L T
T otal bi lir u bin
Dire ct biliru bi n
I n direct bilir ubi n
A l kali ne p h os p hat ase
Ur ic aci d
Al b u m i n
T otal Bile Aci ds ( T B A)
p H
G l uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nit rites
Le u k oc y te esterase
Ur o b ilin o ge n
Uri n e bi liru bi n
Mi crosc o p y b
At scree ni n g o n l y:

F S H c

He pa titis B s urface anti ge n
( Hbs A g)

He pat itis C ( H CV ) 
a nti bo d y

He p B c o re a nti b o d y 
( Hbc A b)

H u ma n i m m u n o defici e nc y
vi r us ( HI V)
At ti mes s pecifie d i n t he
Sc h e d ule of Act i vities:

Uri ne dr u g scree ni n ge
A b bre vi atio ns: A bs = abs ol ut e; A L T = a la nine a mi n o trans ferase; A S T = as p artate a mi n o tra nsferase ; 
- h C G = beta-h u ma n c hori o n ic g o n a d otr o pi n; B U N = bl o o d urea ni tr o gen; C O 2 = car b o n di o xi de ;
F S H = f ollicl e-stim ulati n g h o r m one ; M C H
= mea n c o r p usc ular he m o gl o bi n;  M CH C = mea n c or p usc ular
h e mo g l o bin c o nce ntrati o n ; M C V = mea n c or p usc ular v ol u me; q ual = q ua litati ve; R B C = re d b l o od cell; 
W B C
= w h ite bl o o d cell.
a.
Gl o m er ular F iltrati o n R ate ( GF R) wil l be calc ul ated usi n g t he m o dificati o n of diet i n re nal disease 
(M D R D ) e q uati o n :
G F R ( ml/ m i n/ 1.7 3 m 2) = 1 7 5 x s tan dar di zed Ser u m Creati ni n e-1. 1 5 4 x age -0. 2 0 3 x 1. 2 1 2 
[if blac k] x 0. 7 4 2 [if fe ma le].
b.
O nl y if u ri ne di pstic k is p o sitiv e f o r bl o o d, pr otei n, nitri tes, or le u k oc yte esterase.
c.
F or c o nfir mati o n of p o stme n o p a usal stat us in fe male par tici pa nts o nl y.
 
e.
T he mi ni m u m r e q uire me nt f or d r u g scree ni n g i ncl u des coca i ne, tetrah y dr o ca n na bi n ol ( T H C), 
o piates/ o pi o ids, b e nz o d iaze pin es, a nd a mp heta m i nes ( ot hers are site a n d stu d y  s pecific).
Refl ex testi n g ma y be c o n d ucte d at i n vesti gat or di screti o n; suc h tes ts ma y i nclu de 
P T /IN R /p artial t hr o mb o plasti n t i me (P T T), m y o gl o b i n, creati ne k i nase.
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C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 8 9
In a d diti o n t o t he safety l a b orat or y tests liste d in t he ta ble a b o ve, bl o od sa m ples wi ll be 
c ollecte d a nd a nal yz e d f or a d diti o nal tests as s pecified i n t h e S che d ul e of A ctiv ities.
All a vaila ble r es ults of th e safet y la borat or y  tests liste d i n t he prece di n g ta ble will be 
re vie we d as part of d ose escalati o n.  N ot e that re vie w o f t he f oll o wi n g la b orat or y data is n ot
req uire d pri or t o d ose escalati o n or pr o gre ssi on t o t he ne xt c o h ort /stu d y  part; resu lts will be 
revie we d as t he y bec o me a vaila ble. 

 
 T B A .
La b orat or y /a nalyt e res ults t hat c o ul d u n bli n d t he stu d y  
 will n ot be 
re p orte d to i n ves tig at or sites or ot her bli n de d pers o n n el u ntil t he st u d y h as be en u n bli n d e d;
see als o Secti o n 9. 5 .
 
 
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition
•
An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.
•
NOTE: An AE can therefore be any unfavorable and unintended sign (including an
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis)
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).
•
Exacerbation of a chronic or intermittent preexisting condition including either an
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
Events NOT Meeting the AE Definition
•
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms of 
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the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that
leads to the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from
baseline is not considered an AE.
d. Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct
normal life functions.
•
This definition is not intended to include experiences of relatively minor medical 
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significance such as uncomplicated headache, nausea, vomiting, diarrhea,
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
•
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the Clinical Trial (CT) Serious Adverse Event
(SAE) Report Form to Pfizer Safety.  These requirements are delineated for 3 types of
events: (1) SAEs; (2) nonserious adverse events (AEs); and (3) exposure to the 
investigational product under study during pregnancy or breastfeeding, and occupational
exposure.
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
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Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
None
All (and exposure during 
pregnancy [EDP]
supplemental form for 
EDP)
•
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.
•
The investigator will then record all relevant AE/SAE information in the CRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.
•
There may be instances when copies of medical records for certain cases are
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.
•
The investigator will attempt to establish a diagnosis of the event based on signs,
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not
the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
•
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.
•
Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes
as described in the definition of an SAE, NOT when it is rated as severe.
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Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.
•
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot
be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.
•
The investigator will also consult the investigator’s brochure (IB) and/or product 
information, for marketed products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she
has reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.
•
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
•
If the investigator does not know whether or not the investigational product caused
the event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the CT SAE Report Form and in accordance 
with the SAE reporting requirements.
Follow-up of AEs and SAEs
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
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sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare professionals.
•
If a participant dies during participation in the study or during a recognized
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.
•
New or updated information will be recorded in the originally completed CRF.
•
The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as the data
become available.
•
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form
•
Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.
•
In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or
courier service.
•
Initial notification via telephone does not replace the need for the investigator to
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.
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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention :
•
Refrain from donating sperm.
PLUS either:
•
Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR
•
Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person. 
In addition to male condom use, a highly effective method of contraception will be
considered in woman of childbearing potential (WOCBP) partners of male participants (refer 
to the list of highly effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, or a
WOCBP (see definitions below in Section 10.4.3).
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected
pregnancy. 
10.4.3. Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:
•
Documented hysterectomy;
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•
Documented bilateral salpingectomy;
•
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female.
•
A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause.
•
A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 
•
Female on HRT and whose menopausal status is in doubt will be required to
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
The following contraception methods are be used by women of childbearing potential who 
are partners of male participants in this study:
Highly Effective Methods That Have Low User Dependency
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion.
5. Vasectomized partner.
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•
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has
been confirmed. If not, an additional highly effective method of contraception
should be used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent
1. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation.
•
Oral;
•
Intravaginal;
•
Transdermal;
•
Injectable.
2. Progestogen-only hormone contraception associated with inhibition of ovulation.
•
Oral;
•
Injectable.
3. Sexual abstinence.
•
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent:
•
Male or female condom with or without spermicide;
•
Cervical cap, diaphragm, or sponge with spermicide;
•
A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods).
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Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:
•
A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;
•
An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).
•
A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed
during his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form,
regardless of whether an SAE has occurred.  In addition, the investigator must submit
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done
irrespective of whether an AE has occurred and within 24 hours of awareness of the
exposure.  The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
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Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs
follows: 
•
Spontaneous abortion includes miscarriage and missed abortion;
•
Neonatal deaths that occur within 1 month of birth should be reported, without regard
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to
exposure to the investigational product. 
Additional information regarding the EDP may be requested by the sponsor.  Further
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his
partner.
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P a ge 1 0 1
 
 
 
 
 
 
 
 
 
 
  
 
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased. This occurrence is still regarded as a potential DILI. Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:
•
Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value
<2 × ULN or not available.
•
For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
•
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is
smaller).
•
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible,
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international
normalized ratio (INR), TBA, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial
abnormalities to determine etiology.  A detailed history, including relevant information, such
as review of ethanol, acetaminophen (either by itself or as a coformulated product in 
prescription or over-the-counter medications), recreational drug, supplement (herbal) use and 
consumption, family history, sexual history, travel history, history of contact with a 
jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and potential
occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no
other reason for the liver function test (LFT) abnormalities has yet been found.  Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT
abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of
reasonable investigations have been received and have excluded an alternative etiology.
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events (AEs)
•
Marked sinus bradycardia (rate <40 bpm) lasting minutes.
•
New PR interval prolongation >280 msec.
•
New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.
•
New-onset atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.
•
New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration.
•
Frequent premature ventricular complexes (PVCs), triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events (SAEs)
•
QTcF prolongation >500 msec.
•
New ST-T changes suggestive of myocardial ischemia.
•
New-onset left bundle branch block (QRS >120 msec).
•
New-onset right bundle branch block (QRS >120 msec).
•
Symptomatic bradycardia.
•
Asystole:
•
In awake, symptom-free participants in sinus rhythm, with documented periods 
of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node. 
•
In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 
•
Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate
>120 bpm.
•
Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).
•
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate
<40 bpm), accelerated idioventricular rhythm (40< x <100), and 
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monomorphic/polymorphic ventricular tachycardia >100 bpm (such as torsades de 
pointes).
•
Type II second-degree (Mobitz II) AV block.
•
Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events
•
Change in pattern suggestive of new myocardial infarction.
•
Sustained ventricular tachyarrhythmias (>30 seconds’ duration).
•
Second- or third-degree AV block requiring pacemaker placement.
•
Asystolic pauses requiring pacemaker placement.
•
Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.
•
Ventricular fibrillation/flutter.
•
At the discretion of the investigator, any arrhythmia classified as an adverse
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.
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1 0. 8. A p pe n di x 8 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b br e viati o ns t hat ma y be u se d i n t he pr ot oc ol.
A b bre vi ati o n 
Ter m
A bs
A bs o lute
A E
A d ver se ev e nt
A e 2 4
A m o u nt of u nc ha n g ed dr u g rec o vere d o ver 2 4 h o urs
A L T
A lani ne am i n otran sferase
A S T
A s partate a min otra n sferase
A U C
A rea u n d e r t he co n centrati o n -tim e c ur ve
A U C inf
A rea u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi n it y
A U C last
Area u n der t he 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 b le c o nce nt rati o n
 
A U C 4
A rea u n de r t he cur ve o ver 4 h o u rs
A U C 2 4
A rea u n de r t he c once ntrati o n -ti me cu r ve o ver 2 4 h o u rs
A U C i nf
Are a u n der t he co nce ntrati o n -ti me c urv e t o i nfi nit y
A V
A tri ov e ntric ular
-h C G
Be ta- h uma n c h ori o nic g o na d otr o p i n
B MI
B o d y ma ss i n de x
B P
B lo o d pr essu re
B p m
B eats per m in ute
B U N
B l oo d ur ea n itr o ge n
C F R
C o de of Fe d er al R e g ulatio ns
 
CI O M S
C o u n cil f or Int er nati o nal Or ga ni zatio ns o f Me dical S cie nces
C K
C reatin e kin ase
C Lr
Re nal cleara nce
C m a x
M a x i mu m o bser ve d c o nce ntrat io n
C O 2
C ar b o n di o xi de ( bicar b o na te)
C O N S O R T
C o ns oli d ate d S ta n dar ds of Re p or ti n g T rials
C R F
C ase re po rt f or m
C R O
C o n tract rese arch or ga n iz atio n
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

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A b bre vi ati o n 
Ter m
C R U
C li nical researc h u nit
C S R
C li nical st u dy re p ort
C T
C li nical trial
D C T
D ata c ollect io n t o o l
DI LI
D r ug -i n d uce d liv er inj u ry
D M C
D ata mo nit o rin g c o m mittee
D P P -4i
Di p epti d y l pe ptidase -4 i n hi bit ors 
D U
D is pe nsa ble u nit
E C
E th ics c o mmi ttee
E C G
E lectr ocardi o gr am
e CR F
Ele ctro n ic case rep o rt fo r m
E D P
E x p o s ure d uri ng pr e g na nc y
E D R
E xte m p o ra ne o us dis pens i n g rec or d
e G F R
E stim ate d gl o me r ular filtrati o n rate
E M A
E u ro pe a n Me d ici nes A ge nc y
E U
E ur o pe an U n i o n
E u dra C T
E ur o pea n Cli nical T rials D ata base
F S B G
F i n gerstic k bl oo d gl u c ose
F S H
F oll icle-sti mu latin g h or m o ne
F U
F oll o w -u p
G C P
G o o d C linical P ractice
G F R
G l om er ular filtratio n rate
G G T
G am m a-gl uta m yl  transf e rase
G L P -1
Gl u ca g o n -like pe pt i de-1
G L P -1 R
Gl u ca g o n -like pe pt ide -1 rece pt or
H o r h r
H o u r
H b A 1c
G l ycate d he m o gl o bi n
H B c A b
H e patitis B c ore a nti b o dy
H Bs A b
H epat itis B s u rface an tib o d y
H Bs A g 
H e patitis B s urface a ntig en
H C V A b
H e patitis C a nti b o d y
HI P A A
Healt h I ns ura nce P orta bili ty a n d A cc o u nt a bility A c t
HI V
H u ma n i m m u n o d eficien cy vir u s
H R T
H or m o n e re placem e n t th erap y
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 0 8
A b bre vi ati o n 
Ter m
IB
In vesti gat or’s b r och ur e
I C D
Inf or m ed co n se nt d ocu m e nt
I C H
I nterna ti o nal C o u ncil f or Harm o nisati o n
I D
Id entificati o n
I ND
In ves ti gati o nal ne w dr u g ap p licatio n
I N R
Int er nati onal n or ma lize d rati o
IP
In vesti g ati o nal pr o d uct 
IP ma n ual
In ve sti gati ona l pr o d uct ma n ual
I RB
In stit utio na l re view b o ar d
I R T
Intera cti ve resp o n se tec h n olo g y
I UD
Intra uteri ne de vic e
I US
Intra u terine h or m o n e-releasi n g s ys te m
IV
Intr av e n ous
IW R
Int eracti ve Web -b ase d resp o n se
K 2E D T A
D i p otassi u m et h yle ne di am i netetraacetic aci d
K g
K il o gra m
L B B B
L eft b u nd le bra nc h bloc k
L F T
L i ver fu nct i o n test
M A D
M ul ti ple asce n di n g d ose
 
M C H
M ea n c orp usc ular h em o g l obi n
M C H C
M ea n c or p usc ul ar h e m o gl ob i n co nce ntra ti o n
M C V
M ea n c or p uscu lar v ol u me
M E N 2
M ul ti ple e n d ocri ne ne o plasia sy n dr o m e ty p e 2
M g/ d L
M illi gram( s) p er deciliter
µ m ol/ L
M icro m ole p er liter
M D R D
M o d ificati o n of diet i n r en al di sease
mi n
M i n ute or mi n im u m
M sec
M illisec o n d
M T C
M e dulla ry t hy r oid ca ncer
M T D
M axi m u m t olerate d d ose
N/ A
N o t a p plica ble
N
N u m ber
N C
N ot calc ulate d
N H P
N o n -h u m an pr im ate 
n M
N an o m olar
N O A E L
N o -o bs erve d -ad vers e-effect le vel
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 0 9
A b bre vi ati o n 
Ter m
N S AI D s
N o n -ster oidal a nti -i nfla m mato r y dr u g s
 
P C D
P ri mary c o m pleti o n da te
P G x 
P ha r maco g e n o mic(s)
PI
P rinci pal i n vest i gat or
P K
P h ar mac o ki netic(s)
P T
P r oth ro m bi n ti me
 
P T T
Partial t h r o mb o plasti n ti me
P V C
P rem at ure v e ntricu lar c o ntractio n/ c o m ple x
Q D
D ail y
Q T
D ur ati o n of v e ntric ular de p ol ariz ati o n a n d s u bse q ue nt 
re p olarizati o n. Dura ti o n resi des bet we e n be gi n ni n g of Q R S c o m plex 
t o en d of t he T wa ve.
Q Tc
C orr ecte d Q T
Q T cF
C o rrecte d Q T (F ri dericia met h o d)
Q ua l
Q u alitati ve
 
R B C
R e d bl o o d cell
S A E
S eri o us a d verse e ve nt
S A P
S tatistical a nal ysis plan
S Cr
S er u m creati ni ne
S D
Sta n dar d de v iati on
S G L T 2
S o d i u m-gl uc os e c otra nsp or ter-2
S o A
S ch ed ule o f activ ities
S O P
S tan dar d o per ati n g pr oc e du re
S R S D
S i n gle referen ce safety d oc u me nt
S S
S tea d y state
S S R Is
S elective serot o n i n re u pta ke i n hi bit or s 
S T o D
S t u d y tea m o n de ma n d
S U S A R
S us pec te d un ex pecte d se rio us a d verse react io n
t½
H alf life
T 2 D M
T y pe 2 di a betes mellitus
T B D
T o be deter mi ne d
T B A
T otal b ile aci ds
T Bili
T o tal bil ir u bin
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 1 0
A b bre vi ati o n 
Ter m
T H C
T etrah y dr oca n na bi n o l
T ma x
T i me t o ma xi mu m co nc e ntrati on
T S H
T h y roi d sti mulati n g h or m o ne
T Z D s
T hi az oli dine d io n es
U L N
U p p er li mit o f n or mal
U S
U n ite d States
 
W B C
W h ite bl o o d cell
W O C B P
W o m an o f c hil d beari ng p ote ntial
W O N C B P
W o m an o f n o n -chil d b eari n g pot e ntial
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 1 1
1 1. R E F E R E N C E S
1.  
O rsk o v C , H olst JJ, K n u htse n S , et al. Gl uc a go n -li ke p e ptid es GL P- 1 a n d G L P- 2, 
pre di cte d p r o d ucts of t he gl uca g o n gene, are se crete d se paratel y f r om 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.
Kr e yma n n B, Wil lia 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 ys i olo g ical i ncreti n i n m a n. La n cet 1 9 8 7; 2( 8 5 7 1 ): 13 0 0- 4.
3.
Na uc k M A, Nie der eic h holz U, Ettler R , et al. Gl uca g o n -lik e p e ptid e 1 i n hi b iti o n of 
gastr ic e m ptyi n g o ut w ei g hs its i ns uli notr o pic effec ts i n hea lth y  h u ma ns. A m J P h y si ol 
1 9 9 7; 2 7 3( 5 ): E 98 1- 8.
4.
Fli n t A, R a be n A, Astr u p A, et al. Gl uc a g on- li ke p e pti de 1 p r o m otes satiety a n d 
su p pres ses e nerg 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 D ia betes Atl as 8 t h E di tio n:. h tt p:// w w w.i df. or g/dia b et esatlas.
6.
Me n ke A , Casa gra nde S, Geiss L,  et al. Pre val e nce of a n d Tre n ds i n D i ab etes Am o n g 
A d ults in t he U ni te d States, 1 9 8 8- 2 0 1 2.  J AM A 2 0 1 5; 3 1 4 ( 1 0): 10 2 1.
7.
H u F B . Gl o balizati on of di a betes: the role o f diet, lifestyl e an d ge nes . Di a betes Care 
2 0 1 1 ; 34 ( 6): 12 4 9 - 5 7.
8.
De Fr o nz o R A . Fr o m t he tri u m virate t o t he o m ni ous oc tet: a ne w para di gm for t he 
treatme nt o f t ype 2 dia be tes mellit us. Dia betes 2 0 0 9; 5 8 ( 4): 7 7 3-9 5.
9. 
S tratt o n IM,
A dler AI , Neil HA W , et al. As s ociati on of gl yc ae mia wit h m acr o vasc ular
a nd micr o v asc ular c o m pl icati o ns of t yp e 2 dia b etes ( U K P D S 3 5): p r os pective 
o b ser vati o nal stu d y . B MJ 2 0 0 0;3 2 1( 7 2 5 8) : 40 5- 1 2.
1 1.
A merica n Dia be tes Ass ociati o n. P har ma c olo g ic A p pr oa c hes t o G l yce mic T reat ment: 
St a ndar ds of Me dical Care i n Dia betes— 2 0 1 9
A meric a n Dia betes Ass oci ati o n. Dia be tes
Car e 2 0 1 9 J an; 4 2 (S u p ple m e nt (S u p pl .1 ): S 9 0- S 1 0 2 .
.
1 4.
Pe tri K C C , I ng werse n S H, Fli nt A, e t al. E x p osu re-res p o nse a nal ys is f or e val uati o n of
se ma gl uti de d ose le vels i n t ype 2 dia betes. Dia be tes O bes Meta b 2 0 1 8; 2 0( 9): 2 2 3 8 - 4 5.
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI
C CI
C CI

P F -0 7 0 8 1 5 3 2
P r ot ocol C 3 9 9 1 0 0 2
F i nal Prot oc ol , 1 6 Ja n uar y 2 02 0
P FI Z E R C O N FI D E N TI A L
P a ge 1 1 2
 
 
0 9 0 1 7 7 e 1 9 9 5f 4 7 6 9\ 0. 1\ Dr aft\ V er si o n e d O n: 1 6- F e b- 2 0 2 2 0 6: 3 7 ( G M T)
C CI