A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Chronic Rhinosinusitis (CRS) With or Without Nasal Polyps
Phase: PHASE3
Conditions: Chronic Rhinosinusitis (CRS) With and Without Nasal Polyps
Sponsor: Pfizer

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
D R U G:
B H V - 3 0 0 0 ( P F-0 7 8 9 9 8 0 1) (ri me ge pa nt)
S T U D Y N U M B E R( S):
B H V 3 0 0 0 - 3 1 6 ( C 4 9 5 1 0 1 5)
P R O T O C O L TI T L E:
A P hase 2 / 3, D o u ble-Bli n d, Ra n d o mize d, Place b o -
C o ntr olle d , Safet y a n d Efficac y Trial of B H V-3 0 0 0 
(ri me ge pa nt) Orally Disi nte grati n g Ta blet ( O D T) f or t he 
Ac ute Treat me nt of C hr o nic R hi n osi n usitis ( C R S) Wit h 
or Wit h o ut Nasal P ol y ps
I N D N U M B E R:
I ND 1 5 8 9 5 7
S P O N S O R:
Pfizer I nc. 
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
O RI GI N A L P R O T O C O L D A T E:
2 1 Oct o ber 2 0 2 1
V E R SI O N N U M B E R:
4. 0
V E R SI O N D A T E:
1 4 J ul y 2 0 2 3
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he re q uest of 
c o u ntr y healt h a ut h orities a n d IR Bs/ E Cs, a n d a n y pr ot oc ol a d mi nistrati ve c ha n ge letter (s).
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E
Versi o n 4. 0 – A me n d me nt 3 ( 0 7 J ul y  2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt: C ha n ge i n s p o ns ors hi p fr o m Bi o ha ve n t o Pfizer wit h 
ali g n me nt of t he pr ot oc ol te m plate.
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
S u bst a nti al M o dific ati o n(s)
Refere nce d st u d y n u m ber 
B H V 3 0 0 0 -3 1 6 t o C 4 9 5 1 0 1 5 
a n d c o m p o u n d na me B H V-
3 0 0 0 t o P F -0 7 8 9 9 8 0 1 t o 
reflect i de ntificati o n c ha n ges 
b y  s p o ns or.
Reflects c ha n ge i n s p o ns ors hi p p r ot oc ol 
a n d c o m p o u n d i de ntificati o n n u m bers
S t u d y Sy n o psis
1. 1 Bac k gr o u n d 
1. 3 St u d y  Rati o nale
7. 1. 1 I n vesti gati o nal 
Pr o d uct Hea ders
Title pa ge
S p o ns or na me c ha n ge d
R eflects tra nsfer of s p o ns ors hi p fr o m 
Bi o ha ve n P har mace uticals H ol di n g 
C o m pa n y  Li mite d t o Pfizer I nc.
T hr o u g h o ut t he 
d oc u me nt
Refere nce d st u d y n u m ber 
B H V 3 0 0 0 -3 1 6 t o C 4 9 5 1 0 1 5 
a n d c o m p o u n d na me 
B H V 3 0 0 0 t o P F -0 7 8 9 9 8 0 1 t o 
reflect i de ntificati o n c ha n ges 
b y  sp o ns or
T o ref lect s p o ns ors hi p c ha n ge, pr ot oc ol
a n d c o m p o u n d i de ntificati o n n u m bers
Pr ot oc ol c o ver pa ge 
St u d y  sc he matic
1. 1 Bac k g r o u n d
1. 3 St u d y  rati o nale
4. 2 Sc he d ule of 
Assess me nts
Pla n ne d n u m ber of s u bjects 
ra n d o mize d i ncrease d (fr o m 
a p pr o xi matel y 2 5 0 t o 
a p pr o xi matel y 2 8 6)
T o acc o u nt f or t he perce nta ge of s u bjects 
n ot ha vi n g a facial pai n/ press ure/f ull ness 
w hic h reac hes pai n i nte nsit y  of ≥6 o n 
t he N R S ( 0- 1 0)
St u d y  S u m mar y 
( S yn o psis)
1. 3. 1 St u d y  desi g n 
rati o nale
5. 1 N u m ber of 
S u bjects
4. 2. 2 Ac ute 
treat me nt 
( Ra n d o mizati o n) 
p hase
9. 2 Sa m ple size
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
I ncl usi o n criteri o n # 1 “ Si g ne d 
writter n I nf or me d C o nse nt” 
delete d
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
5. 2. I ncl usi o n 
Criteria
I ncl usi o n criteri o n # 2. b a n d 
E xcl usi o n criteri o n # 4.a f or 
re pr o d ucti ve stat us u p date d
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
5. 2. I ncl usi o n 
Criteria
5. 3. E xcl usi o n 
Criteria
A d diti o n of a n e xcl usi o n 
criteri o n # 7.i f or site staff, 
s p o ns or e m pl o yees a n d 
fa milies
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
5. 3. E xcl usi o n 
Criteria
A d diti o n o f a n e xcl usi o n 
criteri o n # 7.j “ S u bject u na ble 
t o c o m plete e Diar y 
i n de pe n de ntly i n t he o pi ni o n 
of t he I n vesti gat or . ”
T o e ns ure e Diar y  data is c ollecte d 
a p pr o priatel y
5. 3. E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 2.a f or 
b o d y  mass i n de x c ha n ge d t o 
> 3 5. 0 k g/ m 2 (i nstea d of  ≥ 
3 3. 0 k g/ m 2)
T o ali g n wit h t he defi niti o n of all Class 1 
O besit y  s u bjects
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 2. b f or 
“ HI V disease” delete d
T o ali g n wit h ri me ge pa nt prescri bi n g 
i nf or mati o n w here t here is n o 
co ntrai n dicati o n f or use
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 2.j f or 
“ Hist or y of he mat ol o gic or 
s oli d mali g na nc y dia g n osis 
wit hi n 5 y ears pri or t o 
scree ni n g” delete d
E xcl usi o n criteri o n alrea d y  c o vere d i n 
a n ot her E xcl usi o n criteri o n a n d t o ali g n 
wit h ri me ge pa nt prescri bi n g i nf or mati o n 
w here t here is n o c o ntrai n dicati o n f or 
use
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 5.a f or 
e G F R criteria c ha n ge d t o <
3 0 ml/ mi n/ 1. 7 3 m 2
All o we d f or s u bjects wit h m o derate 
re nal i m pair me nt t o be i ncl u de d i n t he 
trial c o nsiste nt wit h t he prescri bi n g 
i nf or mati o n
5. 3 E xcl usi o n 
Criteria
E xcl usi o n criteria # 5. b-e f or 
“ Q Tc F, Left B u n dle Bra nc h 
Bl oc k, Ri g ht B u n dle Bra nc h 
Bl oc k a n d I ntra C o n d ucti o n 
defect” delete d 
T o ali g n wit h ri me ge pa nt prescri bi n g 
i nf or mati o n w here t here is n o 
co ntra i n dicati o n f or use
5 . 3 E xcl usi o n 
Criteria
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
E xcl usi o n criteri o n # 5. b f or 
“E C G a b n or malities t hat, i n 
t he In vesti gat or’s o pi ni o n, 
ma kes t he s u bject u ns uita ble 
f or partici pati o n i n t he st u d y” 
a d de d
T o i ncrease st u d y  i ncl usi vit y a n d t o ali g n 
wit h ri me ge pa nt pr escri bi n g i nf or mati o n 
w here t here is n o c o ntrai n dicati o n f or 
use
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 5.f f or 
li ver e nz ymes ( A L T a n d 
A S T) c ha n ge d t o > 2 x U L N 
(i nstea d > 1 x U L N) a n d # 5.c 
t otal bilir u bi n c ha n ge d t o 
> 1. 5 x U L N ( i nstea d > 1 x 
U L N). F or Gil bert’s 
s yn dr o me, direct bilir u bi n 
> U L N is e xcl usi o nar y .
T o ali g n wit h ri me ge pa nt prescri bi n g 
i nf or mati o n w here t here is n o 
c o ntrai n dicati o n f or use
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 5.e f or 
H b A 1c c ha n ge d t o > 7. 5 % 
(i nstea d of  ≥ 6. 5 %)
T o all o w t he i ncl usi o n of well c o ntr olle d 
dia betics, ali g ne d wit h ri m ge pa nt 
prescri bi n g i nf or mati o n w here t here is 
n o e xcl usi o n f or s u bjects wit h dia betes
5 . 3 E xcl usi o n 
Criteria
E xcl usi o n criteri o n # 6.f f or 
pri or m o n ocl o nal a nti b o d y  
use c ha n ge d fr o m 6 m o n t hs t o 
3 m o nt hs pri or t o scree ni n g
T o i ncrease st u d y  i ncl usi vit y a n d t o ali g n 
wit h ri me ge pa nt prescri bi n g i nf or mati o n 
w here t here is n o c o ntrai n dicati o n f or 
use
5 . 3 E xcl usi o n 
Criteria
5. 4 Pr o hi bite d 
Me dicati o ns
A d diti o n of a n e xcl usi o n 
criteri o n # 6.j “ Use of a n y 
pr o hi bite d c o nc o mita nt 
me dicati o n(s) as s pecifie d i n 
Secti o n 5. 4.”
T o ali g n wit h Secti o n 5. 4 Pr o hi bite d a n d 
Restricte d C o nc o mita nt Me dicati o ns
5. 3. E xcl usi o n 
Criteria
As piri n d ose all o we d c ha n ge d 
fr o m 8 1 m g t o u p t o 1 0 0 m g
T o ta ke i nt o acc o u nt c o m m o nl y 
prescri be d d ose i n car di o vasc ular 
pr o p h y la xis
5. 4 Pr o hi bite d a n d 
Restricte d 
C o nc o mita nt 
Me dicati o ns
G ui da nce relati ve t o W o me n 
of C hil beari n g P ote ntial 
re place d wit h C o ntrace pt i o n 
secti o n a n d A p pe n di x III
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
5. 6 C o ntrace pti o n
1 6. 3 A p pe n di x III : 
C o ntrace pti ve a n d 
Barrier G ui da nce
A d diti o n of g ui da nce relati ve 
t o a b n or mal la b orat or y tests
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
6. 2. 4 L a b orat or y 
assess me nts
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
A d diti o n of g ui da nce relati ve 
t o E C G ma na ge me nt a n d 
a d diti o n of a ne w a p pe n di x 
relati ve t o EC G fi n di n gs of 
P ote ntial Cli nical C o ncer n
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
6. 2. 2 E C G
1 6. 2: A P P E N DI X II: 
E C G fi n di n gs of 
P ote ntial Cli nical 
C o ncer n
State me nt re gar di n g a n y 
“ yes” res p o nses o n t he C-
S S R S q uesti o n naire u p date d
T o ali g n wit h E xcl usi o n criteri o n # 7.f 
6. 2. 5 C ol u m bia -
S uici de Se verit y  
Rati n g Scale ( C -
S S R S)
Re m o ve d N o n -I n vesti gati o nal 
Pr o d uct secti o n
N ot a p plica ble f or t his st u d y
7. 1. 2. N o n -
I n vesti gati o nal 
Pr o d uct
P ote ntial DI LI cases 
i de ntificati o n a n d 
ma na ge me nt u p date
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses 
8. 5 P ote ntial Dr u g 
I n d uce d Li ver I nj ur y 
( DI LI)
U p date d O ver d ose secti o n
T o clarif y  t hat o nly o ver d ose ass ociate d 
wit h a n S A E is re p orta ble t o Pfizer 
Safet y  
8. 3 O ver d ose
Re -scree ni n g p olic y u p date d
T o all o w a n d defi ne rescree ni n g criteria 
f or pre vi o usly scree n faile d s u bjects
4. 2. 1 Scree ni n g 
p hase
U p date d t he i nf or mati o n 
a b o ut t he k n o w n a n d 
e x pecte d be nefits a n d ris ks 
a n d reas o na bl y e x pecte d A Es 
of r i me ge pa nt a n d refere nce d 
t o t he In vesti gat or Br oc h ure
T o ali g n wit h I n vesti gat or br oc h ure
1. 2 Pr o d uct 
de vel o p me nt 
bac k gr o u n d
1. 3. 4 Be nefit/ Ris k 
assess me nt
D escri pti o n of pri mar y 
esti ma n d a d de d
Pri mar y  esti ma n d descri pti o n was n ot 
i ncl u de d i n earlier pr ot oc ol versi o ns
9. 3 P o p ulati o ns f or 
A nal y sis a n d 
Esti ma n ds
D elete d  “s u bject as r a n d o m 
effect “ a n d  c ha n ge d 
“ge ner alize d li ne ar mixe d 
effect m o del ” t o “li ne ar 
m o del ” fr o m t he m o del 
s pecificati o n of pri mar y a n d 
sec o n dar y a nalys is
A re peate d meas ure wit hi n s u bject is 
alrea d y c o nsi dere d i n M M R M a nal y sis 
t o a d dress wit hi n s u bject c orrelati o n. 
A d diti o nal s pecificati o n of ra n d o m effect 
f or s u bject is mislea di n g t o t he c o nte xt.
9. 4. Statistical 
met h o ds
A d diti o n of “ Se nsiti vit y  
a nal ys is”
R o b ust nes s of pri mar y esti ma n d ( M A R 
ass u m pti o n) will be verifie d t hr o u g h 
a d diti o nal se nsiti vit y a nal ysis
9. 4. 2 Pri mar y  
E n d p oi nt(s)
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Re place d “ str atifie d 
C oc hr a n- M a ntel -H ae nszel 
( C M H) test … str atific ati o n 
f act or as...” wit h “M a ntel -
H ae nszel risk esti m ati o n …. 
str atific ati o n by …"
C orrect refere nce t o test pr oce d ure
9. 4. 3. Sec o n dar y  
E n d p oi nts
A d diti o n of t he secti o n 
re gar di n g S p o ns or’s 
Me dicall y  Q ualifie d 
I n di vi d ual
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 0. 6 S p o ns or’s 
Me dicall y  Q ualifie d 
I n di vi d ual
D eleti o n of tacr oli m us
T o a li g n wit h n o ncli nical a n d cli nical 
dr u g t o dr u g i nteracti o n i nf or mati o n 
a vaila ble o n ri me ge pa nt
1 6. 1 A P P E N DI X I: 
Str o n g I n hi bit ors a n d 
Str o n g a n d M o derate 
I n d ucers of C Y P 3 A 4 
Pr otei n ( N ot all -
i ncl usi ve)
A d diti o n of m o derate 
C Y P 3 A 4 i n d ucers
T o ali g n wit h n o ncli nical a n d cli nical 
dr u g t o dr u g i nteracti o n i nf or mati o n 
a vaila ble o n ri me ge pa nt
1 6. 1 A P P E N DI X I: 
Str o n g I n hi bit ors a n d 
Str o n g a n d M o derate 
I n d ucers of C Y P 3 A 4 
Pr otei n ( N ot all -
i ncl usi ve)
A d diti o n of C o ntrace pti ve 
a n d Barrier Gui da nce
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 6. 3 A P P E N DI X III: 
C o ntrace pti ve a n d 
Barrier G ui da nce
Defi ne d E n d of St u d y
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
4. 1 St u d y  Desi g n 
a n d D urati o n
N o n -s u bst a nti al M o dific ati o n(s)
Clarifie d I P a d mi nistrati o n
T o ali g n wit h Secti o n 7. 2. 2 Selecti o n a n d 
Ti mi n g of D ose a n d A d mi nistrati o n
1. 3. 1 St u d y  Desi g n 
Rati o nale
4. 1 St u d y  Desi g n 
a n d D urati o n
U p date d t he Seri o us A d verse 
E ve nt ( S A E) a n d pre g na nc y  
re p orti n g desti nati o n a n d 
electr o nic re p orti n g s ys tem ; 
u p date d S A E re p orti n g 
re q uire me nts
T o i nc or p orate t he n o n -s u bsta ntial 
c ha n ges descri be d i n pre vi o us P A C L  
date d 2 8 A pr 2 0 2 3
8. 1. 2 C ollecti o n a n d 
re p orti n g Seri o us 
A d verse E ve nts 
8. 4 Pre g na nc y
A d diti o n of Pre g na nt Part ner 
Release of I nf or mati o n F or m
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
8. 4 Pre g na nc y
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
U p date d t he n o n -Seri o us 
A d verse E ve nts re p orti n g 
starti n g p oi nt
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses re gar di n g A E re p orti n g 
starti n g p oi nt
8. 2. 1 C ollecti o n a n d 
re p orti n g of n o n-
Seri o us A d verse 
E ve nts
Re p orti n g re q uire me nts 
a d de d f or :
E n vir o n me ntal E x p os ure, 
E x p os ure D uri n g 
B reastfee di n g, Occ u pati o nal 
E x p os ure ;
Lac k of E fficac y;
Me dicati o n E rr ors;
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
8. 7 E n vir o n me ntal 
E x p os ure, E x p os ure 
D uri n g 
Breastfee di n g a n d 
Occ u pati o nal 
E x p os ure
8. 8 L ac k of Efficac y
8. 9 Me dicati o n 
Err ors
A p pr o xi mati ve n u m ber of 
sites a n d st u d y d urati o n 
delete d
T o ali g n wit h Pfizer’s sta n dar ds
5. 1 N u m ber of 
s u bjects
Clarifie d t hat dail y  
me dicati o n d oses m ust be 
sta ble f or at least o ne m o nt h 
pri or t o t he Scree ni n g Visit 
a n d t hr o u g h o ut t he st u d y
C orrecti o n
5. 5 Dail y  a n d 
Resc ue Me dicati o ns
A d diti o n of refere nce t o 
Q ualit y  T olera nce Li mits a n d 
re na me d t he secti o n
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
5. 8 Pr ot oc ol 
de viati o ns a n d 
Q ualit y  T olera nce 
Li mits
A d diti o n of I n vesti gati o nal 
Pr o d uct ma n ual a n d P re g na nt 
Part ner Release of 
I nf or mati o n F or m; U p date d 
f or ms a n d re m o ve d refere nce 
t o e C R F f or S A E re p orti n g
T o ali g n wit h Pfizer’s pr ocesses
6. 1 St u d y  materials
Re place me nt of “ P har mac y  
Ma n ual” wit h 
“I n vesti gati o nal Pr o d uct 
Ma n ual”
a n d re m o val of 
“ h u mi dit y” fr o m 
e n vir o n me ntal c o n diti o n
re q uire me nts
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
7. 1. 2 Pac ka gi n g, 
S hi p me nt a n d 
St ora ge
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
State me nt re gar di n g p u blic 
re gistrati o n of P hase 1 trials 
i n p u blicl y accessi ble 
data base delete d. S tate me nt 
re gar di n g Pri nci pal 
I n vesti gat or a n d t he s p o ns or’s 
re prese ntati ve si g nat or y 
delete d. S p o ns or’s re g ulat or y  
a n d et hics res p o nsi bilities 
a d de d
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 0. 1 G o o d Cli nical 
Practice
Ne w secti o n re gar di n g 
Disse mi nati o n of Cli nical 
St u d y  Data
T o ali g n wit h Pfizer’s sta n dar ds 
re gar di n g disse mi nati o n of Cli nical 
St u d y  Data
1 0. 2 Disse mi nati o n 
of Cli nical St u d y  
Data
Clarifie d t hat s u bject m ust 
si g n a n d date a n I R B/I E C 
a p pr o ve d writte n i nf or me d 
c o nse nt f or m f or st u d y
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 0. 4 I nf or me d 
C o nse nt
Re m o ve d state me nt t hat 
I RB/I E C has t o be n otifie d at 
least 5 da ys pri or t o 
i m ple me nti n g pr ot oc ol 
c ha n ge
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 2 A me n d me nts
Secti o n 1 3 “ St u d y re p ort a n d 
P u blicati o ns p olic y ” re na me d 
t o “ P u blicati o n p olic y”; 
se nte nce re gar di n g C S R 
delete d
T o acc o u nt f or t he a d diti o n of Secti o n 
1 0. 2 Disse mi nati o n of Cli nical St u d y  
Data
1 3 P u bl icati o n 
p olic y
Secti o n 1 5 “ C o nfi de ntialit y ” 
re na me d t o “ Data Pr otecti o n” 
a n d u p date d
T o ali g n wit h Pfizer’s sta n dar ds a n d 
pr ocesses
1 5 Data pr otecti o n
M o ve d past pr ot oc ol 
a me n d me nts secti o n 
“ S u m mar y of C ha n ges” t o 
A p pe n di x 
T o ali g n wit h Pfizer’s e dit orial sta n dar ds
1 6. 3 A P P E N DI X IV:
Pr ot oc ol 
A me n d me nt Hist or y
Secti o ns “ C o nfi de ntialit y a n d 
I n vesti gat or state me nt” a n d 
“ Cli nical Pr ot oc ol A p pr o val 
f or m” re m o ve d
T o ali g n wit h Pfizer’s sta n dar ds
C o nfi de ntialit y  a n d 
I n vesti gat or 
state me nt
Cli nical Pr ot o c ol 
A p pr o val f or m
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Re place me nt of “ partici pa nt” 
wit h “s u bject”
F or c o nsiste nc y  t hr o u g h o ut t he pr ot oc ol
T hr o u g h o ut t he 
pr ot oc ol
Re n u m beri n g of I ncl usi o n
an d E xcl usi o n criteria
E dit orial c ha n ge
5 . 2 Incl usi o n criteria
5. 3 E xcl usi o n 
criteria
L ist of a b bre viati o ns u p date d 
T o reflect ne w a b bre viati o ns a d de d t o 
t he Pr ot oc ol a me n d me nt
L ist of a b bre viati o ns
Mi n or gra m matical a n d 
s pelli n g c orrecti o ns; Secti o n 
re n u m beri n g 
C orrecti o ns
T hr o u g h o ut t he 
d oc u me nt
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
S T U D Y S U M M A R Y ( S Y N O P SI S)
Title: 
A P hase 2 / 3, D o u ble-Bli n d, Ra n d o mize d, Place b o -C o ntr olle d, Safet y a n d 
Efficac y  Trial of B H V-3 0 0 0 ( P F-0 7 8 9 9 8 0 1) (ri me ge pa nt) Orally 
Disi nte grati n g Ta blet ( O D T) f or t he Ac ute Treat me nt of C hr o nic 
R hi n osi n usitis ( C R S) W it h or W it h o ut Nasal P ol y ps
R ati o n ale: 
C hr o nic r hi n osi n usitis ( C R S) is a s y m pt o matic i nfla m mati o n of t he para nasal 
si n uses a n d nasal ca vit y lasti n g m ore t ha n 1 2 wee ks. Br oa dly, it ca n be di vi de d 
i nt o t w o p he n ot ypes: C R S wit h a n d wit h o ut nasal p ol y ps. T y picall y, it prese nts 
wit h facial pai n/ pres s ure/f ull ness, nasal o bstr ucti o n (c o n gesti o n), nasal 
disc har ge, a n d/ or decrease d se nse of s mell. C R S affects a p pr o xi matel y 5-1 2 % 
of t he U S p o p ulati o n a n d is ass ociate d wit h re d uce d q ualit y  of life a n d 
si g nifica nt healt h care b ur de n. 1 - 3
T he mai nsta y  of treat me nt are t o pical nasal c ortic oster oi ds a n d sali ne 
irri gati o n; h o we ver, t he efficac y  is ver y li mite d lea vi n g ma n y patie nts wit h o ut 
ac hie vi n g desira ble relief. I n c o ntrast, oral c ortic oster oi ds, l o n g -ter m n o n-
ster oi dal a nti-i nfla m mat or y dr ugs ( N S AI Ds ), or a nti bi otics ma y pr o vi de m ore 
be nefits b ut are ass ociate d wit h si g nifica nt si de effects. Wit h li mite d treat me nt 
o pti o ns a n d i na de q uate disease ma na ge me nt, C R S re mai ns a n area of u n met 
me dical nee d pr o m pti n g de vel o p me nt of disease- s pecific i nter ve nti o ns.4 ,5
T he pr o p ose d st u d y is base d o n t he e v ol vi n g precli nical a n d cli nical e vi de nce 
s u g gesti ng a r ole f or calcit o ni n ge ne-relate d pe pti de (C G R P ) i n t he 
pat h o p h y si ol o g y of C R S. B H V- 3 0 0 0 ( P F-0 7 8 9 9 8 0 1) (ri me ge pa nt) is a s mall 
m olec ule C G R P rece pt or a nta g o nist t hat is bei n g de vel o pe d f or t he p ote ntial 
treat me nt of C R S. T he data fr o m t his st u d y will all o w c haracterizati o n of t he 
safety a n d efficac y of orall y  disi nte grati n g ta blet ( O D T) of ri me ge pa nt vers us 
place b o i n t he treat me nt of chr o nic rhi n osi n usitis wit h or wit h o ut p ol y ps.
T ar get 
P o p ul ati o n:
T he st u d y  will recr uit male a n d fe male s u bjects 1 8 years of a ge a n d ol der wit h 
a hist or y of c hr o nic r hi n osi n usitis wit h or wit h o ut nasal p ol y ps, dia g n ose d b y a 
healt hcare pr o vi der , t hat ha ve ha d at least a t wel ve wee k hist or y  of facial 
pai n / press ure/f ull ness a n d o ne or m ore of t he f oll o wi n g si g ns a n d s y m pt o ms: 
nasal disc har ge (a nteri or, p osteri or, or b ot h), nasal o bstr ucti o n (c o n gesti o n), 
a n d/or decrease d se nse of s mell. S u bjects m ust ha ve ha d i nfla m mati o n 
d oc u me nte d b y o ne or m ore of t he f oll o wi n g fi n di n gs : p ur ule nt ( n ot clear) 
m uc us or e de ma i n t he mi d dle meat us or a nteri or et h m oi d re gi o n ; p ol y ps i n 
nasal ca vit y or t he mi d dle meat us ; a n d/ or ra di o gra p hic i ma gi n g s h o wi n g 
i nfla m mati o n of t he para nasal si n uses.
S u bjects m ust ha ve ha d at least t w o i nsta nces of facial pai n / press ure/f ull ness 
t hat ha d reac he d a c urre nt i nte nsit y of m o derate or se vere o n a 4 -p oi nt rati n g 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
scale (0 = N o ne, 1 = M il d, 2 = M o derate, 3 = S e vere) wit hi n 3 0 da y s pri or t o 
t he Scree ni n g Visit. 
N u m ber of 
S u bjects:
A p pr o xi matel y 2 8 6 s u bjects will be ra n d o mize d t o res ult i n a p pr o xi matel y 2 0 0 
( 1 0 0 per ar m) e val ua ble s u bjects . T he s u bjects will be ra n d o mize d i n a 1: 1 
rati o t o t he ri me ge pa nt or place b o treat me nt gr o u ps. T he ra n d o mizati o n will be 
stratifie d b y t he prese nce of nasal p oly ps ( yes or n o).
O bjecti ves 
( Pri m ar y): 
T o e val uate t he efficac y  of ri me ge pa nt c o m pare d wit h place b o i n t he ac ute 
treat me nt of chr o nic r hi n osi n usitis wit h or wit h o ut p ol y ps o n mea n c ha n ge 
fr o m baseli ne of facial pai n/ press ure/f ull ness o n a N u merical Rati n g Scale 
(N R S ) ( 0-1 0) sc ore at 2 h o urs p ost-d ose.
O bjecti ves 
( Sec o n d ar y):
1.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n 
T otal Nasal S y m pt o m Sc ore ( T N S S) at 2 h o urs p ost -d ose.
2.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n
nasal o bstr ucti o n (c o n gesti o n) sc ore o n N R S ( 0-1 0) sc ore at 2 h o urs p ost -
d ose.
3.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n 
nasal disc har ge sc ore o n N R S ( 0-1 0) sc ore at 2 h o urs p ost -d ose.
4.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n hea dac he pai n relief o n a 
4- p oi nt Li kert scale at 2 h o urs p ost -d ose c o m pare d t o baseli ne .
5.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he pr o ba bilit y of 
re q uiri n g resc ue me dicati o n wit hi n 2 4 h o urs of i nitial treat me nt.
E x pl or at or y O bjecti ves
1.
T o e val u ate ri me ge pa nt c o m pare d t o place b o o n ≥ 3 0 % re d ucti o n fr o m 
baseli ne of facial pai n/ press ure/f ull ness N R S ( 0- 1 0) sc ore at 2 h o urs p ost -
d ose .
2.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 5 0 % re d ucti o n fr o m 
baseli ne of facial pai n/ press ure/f ull ness N R S ( 0- 1 0) sc ore at 2 h o urs p ost -
d ose .
3.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m 
baseli ne of facial pai n/ press ure/f ull ness N R S ( 0- 1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 
9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs p ost -d ose.
4.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m 
baseli ne nasal o bstr ucti o n (c o n gesti o n) N R S ( 0 -1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 
9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs p ost -d ose.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
5.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m 
baseli ne of nasal disc har ge N R S ( 0 -1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes 
a n d 2, 4, 8 a n d 2 4 h o urs p ost- d ose.
6.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o hea dac he pai n 
relief at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs p ost-d ose
c o m pare d t o baseli ne.
7.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he P GI- C q uesti o n naire at 
2 4 h o urs p ost -d ose.
8.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 3 0 % re d ucti o n of facial 
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 2 4 h o urs p ost -d ose .
9.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 5 0 % re d ucti o n of facial 
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 2 4 h o urs p ost -d ose .
1 0. T o e val uate ri me ge pa nt c o m pare d t o place b o o n s ustai ne d relief of facial 
pai n/ press ure/f ull ness, as defi ne d b y  eac h of t he f oll o wi n g: 3 0 % re d ucti o n 
fr o m baseli ne o n N R S ( 0-1 0), 1. 5 -p oi nt re d ucti o n o n N R S ( 0 -1 0), a n d a 2 -
p oi nt re d ucti o n o n N R S ( 0- 1 0) t hr o u g h 2 4 h o urs p ost -d ose.
1 1. T o e x pl ore t he distri b uti o n of baseli ne disease se verit y  usi n g t he of Si n o-
Nasal O ut c o me Test ( S N O T-2 2).
1 2. T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he Si n o -Nasal O utc o me 
Test ( S N O T -2 2) sc ore at 2 4 h o urs p ost -d ose.
1 3. T o e val uate t he safet y a n d t olera bilit y of ri me ge pa nt i n t he ac ute treat me nt 
of c hr o nic r hi n osi n usitis as meas ure d b y t he fre q ue nc y of a d verse e ve nts of 
m o derate or se vere i nte nsit y , seri o us a d verse e ve nts ( S A Es), cli nicall y 
rele va nt la b orat or y a b n or malities, a n d nasal i ns pecti o n a b n or malities.
1 4. T o e val uate ri me ge pa nt c o m pare d t o place b o f or t he C ol u m bia-S uici d e
Se verit y  Rati ng Scale ( C -S S R S).
St u d y Desi g n:
T his is a d o u ble -bli n d, ra n d o mize d, m ultice nter, o ut patie nt e val uati o n of t he 
safety a n d efficac y of ri me ge pa nt as c o m pare d t o place b o f or t he ac ute 
treat me nt of c hr o nic r hi n osi n usitis ( C R S) wit h or wit h o ut nasal p ol yps. T h e 
st u d y dr u g will be ri me ge pa nt prese nte d i n a 7 5 m g O D T or matc hi n g place b o.
S u bjects w h o ha ve c o nse nte d t o st u d y  partici pati o n will first partici pate i n t he 
scree ni n g p hase ( 3 t o 1 4 da y peri o d). S u bjects m ust re mai n o n t he sa me d ose 
of dail y  use of me dicati o ns t o treat C R S s ym pt o ms fr o m scree ni n g t hr o u g h t he 
d urati o n of t he st u d y  a n d ma y n ot start a n y ne w dail y me dicati o n. S u bjects 
meeti n g i nitial eli gi bilit y  criteria will be as ke d t o c o nti n ue t o a Baseli ne Visit.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
At t he Baseli ne Visit, eli gi bilit y  f or c o nti n ue d partici pati o n i n t he st u d y will be 
assesse d bef ore ra n d o mizati o n occ urs a n d bef ore st u d y  me dicati o n is 
dis pe nse d. T he s u bject will be dis pe nse d a si n gle d ose of t he d o u ble -bli n d 
st u d y me dicati o n. T he s u bject will be i nstr ucte d t o ta ke t heir st u d y me dicati o n, 
as a n o ut patie nt, w he n (if) t he y ha ve a facial pai n/ press ure/f ull ness w hic h 
reac hes a c urre nt i nte nsit y of ≥6 o n t he N R S ( 0 -1 0). T he s u bject will c o m plete 
q uesti o n naires o n a n e Diar y  f or 2 4 h o urs after ta ki n g st u d y me dicati o n. T he 
s u bject will be i nstr ucte d t o tele p h o ne t he st u d y ce nter i m me diatel y if a se vere 
or seri o us a d verse e ve nt occ urs.
S u bjects will rec or d efficac y  data i n t heir e Diar y. T his i ncl u des t he f oll o wi n g: 
i nte nsit y of t he facial pai n/ press ure/f ull ness pri or t o a n d at ti me of ta ki n g st u d y 
me dicati o n. S u bject s h o ul d n ot d ose wit h st u d y  me dicati o n u ntil facial 
pai n/ press ure/f ull ness reac hes a c urre nt i nte nsit y of ≥6 o n t he N R S ( 0- 1 0). 
S u bjects will c o m plete Si n o -Nasal O utc o me Test ( S N O T -2 2) q uesti o n naire at 
t he Baseli ne Visit ( o n a pa per scale), a n d  at 2 4 h o urs p ost-d ose, s u bjects will 
c o m plete S N O T-2 2 ( o n t he e Diar y ). Facial pai n/ press ure/f ull ness se verity, 
nasal c o n gesti o n ( o bstr ucti o n) se verit y, a n d nasal disc har ge se verit y will be 
rec or de d usi n g a N R S ( 0 -1 0) j ust pri or t o ta ki n g st u d y  me dicati o n a n d at 1 5, 
3 0, 4 5, 6 0, a n d 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs after d osi n g. T otal Nasal 
S y m pt o m Sc ore ( T N S S) will be calc ulate d as t he s u m of 3 s y m pt o m sc ores: ( 1) 
facial pai n/ press ure/f ull ness; ( 2) nasal o bstr ucti o n (c o n gesti o n); a n d ( 3) nasal 
disc har ge; rec or de d j ust pri or t o ta ki n g st u d y me dicati o n a n d after d osi n g at 
ti me p oi nts of 1 5, 3 0, 4 5, 6 0, a n d 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs. S u bjects 
w h o e x perie nce c urre nt hea dac he pai n of m o derat e or se vere pai n i nte nsit y at 
t he ti me of q ualif yi n g facial pai n/ press ure/f ull ness will rec or d t heir hea dac he 
pai n se verit y usi n g a 4 -p oi nt L i kert scale ( 0 = N o ne; 1 = Mil d; 2 = M o derate; 3 
= Se vere) at ti me of ta ki n g st u d y me dicati o n a n d after d osi n g at t i me p oi nts of 
1 5, 3 0, 4 5, 6 0, a n d 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs. S u bjects will c o m plete 
t he Patie nt Gl o bal Im pressi o n of C ha n ge ( P GI -C) q uesti o n naire 2 4 h o urs after 
d osi n g.
At t he e n d of 2 h o urs after d osi n g wit h st u d y me dicati o n (a n d after t he 2 -h o u r 
assess me nts ha ve bee n c o m plete d o n t he e Diar y ), s u bjects will be per mitte d t o 
use t he f oll o wi n g resc ue me dicati o n: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y ), or 
as piri n, i b u pr ofe n, na pr o xe n ( or a n y  ot her ty pe of n o n -ster oi dal a nti-
i nfla m mat or y dr u g [ N S AI D]), oral a nti hista mi nes ( n o n-se dati n g), oral 
dec o n gesta nts, t o pical nasal dec o n gesta nts, t o pical nasal a ntic h oli ner gics (all 
u p t o t he dail y  rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g). T hese are 
t he o nl y me dicati o ns all o we d f or resc ue treat me nt after 2 h o urs p ost d ose of 
st u d y me dicati o n. At t he e n d of 2 4 h o urs after d osi n g wit h st u d y me dicati o n 
( b ut bef ore t he E n d of Treat me nt Visit), if nee de d, t he y ma y ta ke t heir 
prescri be d sta n dar d of care me dicati o ns pr o vi de d all of t he assess me nts ha ve 
bee n c o m plete d o n t he e Diar y . E xcl usi o nar y resc ue me dicati o n s uc h as o pi oi ds 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
a n d b utal bital c o m p o u n ds are n ot all o we d o n t his st u d y . 
Si milarl y , if t he facial pai n/ press ure/f ull ness is relie ve d b y st u d y me dicati o n at 
2 h o urs after d osi n g b ut t he n rec urs t o a i nte nsit y  of ≥6 o n t he N R S ( 0- 1 0) 
bet wee n 2 a n d 2 4 h o urs, t he s u bject will be per mitte d t o ta ke t he sa me resc ue 
t hera py as o utli ne d a b o ve. I n all circ u msta nces, t he s u bject will al wa ys 
c o nti n ue t o c o m plete his or her e Diar y  f or u p t o 2 4 h o urs after c o ns u mi n g t he 
st u dy me dicati o n. D uri n g t he 4 5 -d a y  treat me nt p hase, if t he s u bject has a n o n -
q u alif yi n g i nsta nce of facial pai n/ press ure/f ull ness (i.e., facial 
pai n/ press ure/f ull ness < 6 o n a N R S [ 0 - 1 0]), t he s u bject is per mitte d t o use 
o nl y  t he f oll o wi n g me dicati o ns t o treat t he s ym pt o ms: aceta mi n o p he n ( u p t o 
1 0 0 0 m g/ da y ), or as piri n, i b u pr ofe n, na pr o xe n ( or a n y ot her ty pe of n o n -
ster oi dal a nti-i nfla m mat or y dr u g [ N S AI D]), oral a nti hista mi nes ( n o n-se dati n g), 
oral dec o n gesta nts, t o pical nasal dec o n gesta nts , t o pical nasal a ntich oli ner gics
(all u p t o t he dail y rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g), t hat 
are n ot ot her wise pr o hi bite d b y  t he st u d y, see Secti o n 5. 4 .
S u bjects s h o ul d ha ve access t o s y ste mic c ortic oster oi ds a n d a nti bi otics d uri n g 
t he trial f or treat me nt of s ym pt o ms, if i n dicate d. H o we ver, s u bjects s h o ul d 
disc o nti n ue t he st u d y  if t he y recei ve t h ose t hera pies. 
S u bjects will ret ur n t o t he st u d y  site wit hi n 7 da ys ( + 2) after ta ki n g st u dy 
treat me nt f or re vie w of t he e Diar y, assess me nt of me dicati o n c o m plia nce, 
a n d m o nit ori n g of t olera bilit y a n d safet y. If a s u bject has N O T e x perie nce d 
a facial pai n/ press ure/f ull ness of s ufficie nt se verit y wit hi n 4 5 da y s after 
ra n d o mizati o n, t he y still are re q uire d t o c o m plete all E O T visit pr oce d ures. 
All s u bjects m ust ret ur n e m pt y  me dicati o n pac ka gi n g, a ny u n use d st u d y 
me dicati o n, a n d t he e Diar y  t o t he st u d y ce nter.  
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
S T U D Y S C H E M A TI C
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) Ac ute Tre at me nt of C hr o nic R hi n osi n usitis Wit h or Wit h o ut 
N as al P ol y ps St u d y
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T A B L E O F C O N T E N T S
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E ...................................... 2
S T U D Y S U M M A R Y ( S Y N O P SI S) ............................................................................................ 1 0
S T U D Y S C H E M A TI C ................................................................................................................ 1 5
T A B L E O F C O N T E N T S ............................................................................................................ 1 6
LI S T O F T A B L E S ....................................................................................................................... 1 9
LI S T O F A B B R E V I A TI O N S ..................................................................................................... 2 0
1
I N T R O D U C TI O N A N D R A TI O N A L E ............................................................................. 2 4
1. 1
B ac k gr o u n d ...................................................................................................................... 2 4
1. 2
Pr o d uct De vel o p me nt B ac k gr o u n d ................................................................................ 2 5
1. 3
St u d y R ati o n ale ................................................................................................................ 2 5
1. 3. 1
St u d y Desi g n R ati o n ale ..............................................................................................2 6
1. 3. 2
D ose Selecti o n R ati o n ale ............................................................................................ 2 7
1. 3. 3
Rese arc h H y p ot hesis .................................................................................................. 2 7
1. 3. 4
Be nefit/ Ris k ................................................................................................................2 7
2
S T U D Y O B J E C TI V E S ........................................................................................................ 2 9
2. 1
Pri m ar y O bjecti ve(s) ....................................................................................................... 2 9
2. 2
Sec o n d ar y O bjecti ve(s) .................................................................................................... 2 9
2. 3
E x pl or at or y O bjecti ve(s) ................................................................................................. 2 9
3
S T U D Y E N D P OI N T S .......................................................................................................... 3 1
3. 1
Pri m ar y E n d p oi nt(s) ........................................................................................................ 3 1
3. 2
Sec o n d ar y E n d p oi nt(s) .................................................................................................... 3 1
3. 3
Me as ures of i nterest ......................................................................................................... 3 1
4
S T U D Y P L A N ....................................................................................................................... 3 2
4. 1
St u d y Desi g n a n d D ur ati o n ............................................................................................. 3 2
4. 2
Sc he d ule of Assess me nts .................................................................................................. 3 3
4. 2. 1
Scree ni n g P h ase ( 3 t o 1 4 d a ys) .................................................................................. 4 2
4. 2. 2
Ac ute Tre at me nt ( R a n d o miz ati o n) P h ase ............................................................... 4 2
4. 2. 2. 1
e Di ar y D at a C ollecti o n ........................................................................................ 4 2
4. 2. 3
E xte nsi o n P h ase.......................................................................................................... 4 4
4. 2. 4
W as h o ut P h ase................................ ...........................................................................4 4
4. 2. 5
E n d of Tre at me nt .......................................................................................................4 4
4. 3
P ost St u d y Access t o T her a p y ......................................................................................... 4 4
5
P O P U L A TI O N ......................................................................................................................4 5
5. 1  
N u m ber of S u bjects................................ ..........................................................................4 5
5. 2
I ncl usi o n Criteri a .............................................................................................................4 5
5. 3 
E xcl usi o n Criteri a................................ ............................................................................4 6
5. 4
Pr o hi bite d a n d Restricte d C o nc o mit a nt Me dic ati o ns .................................................. 5 1
5. 5
D ail y a n d Resc ue Me dic ati o ns ........................................................................................5 2
5. 6
C o ntr ace pti o n ...................................................................................................................5 4
5. 7
Ot her Restricti o ns a n d Prec a uti o ns ...............................................................................5 4
5. 8 
Pr ot oc ol De vi ati o ns a n d Q u alit y T oler a nce Li mits .......................................................5 4
6
S T U D Y C O N D U C T A N D D E S C RI P TI O N O F S T U D Y P R O C E D U R E S .....................5 5
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6. 1
St u d y M ateri als ................................................................................................................ 5 5
6. 2
S afe t y Assess me nts........................................................................................................... 5 6
6. 2. 1
Vit al Si g ns a n d P h ysic al Me as ure me nts ( Hei g ht a n d Wei g ht).............................. 5 6
6. 2. 2
Electr oc ar di o gr a m ( E C G) ......................................................................................... 5 6
6. 2. 3
P h ysic al E x a m ............................................................................................................ 5 6
6. 2. 4
L a b or at or y Assess me nts ............................................................................................ 5 6
6. 2. 4. 1
S afet y L a b or at or y Testi n g .................................................................................. 5 7
6. 2. 4. 2
Pre g n a nc y Testi n g ................................................................................................ 5 8
6. 2. 5
C ol u m bi a -S uici de Se verit y R ati n g Sc ale ( C -S S R S) ................................................ 5 8
6. 2. 6
Wee kl y C o nt act
.......................................................................................................... 5 8
6. 3
Effic ac y Assess me nts ....................................................................................................... 5 8
6. 3. 1
F aci al p ai n/ press ure/f ull ness ..................................................................................... 5 8
6. 3. 2
N as al o bstr ucti o n (c o n gesti o n).................................................................................. 5 8
6. 3. 3
N as al disc h ar ge ........................................................................................................... 5 9
6. 3. 4
He a d ac he p ai n ............................................................................................................ 5 9
6. 3. 5
Resc ue Me dic ati o n ..................................................................................................... 5 9
6. 3. 6
P atie nt Gl o b al I m pressi o n of C h a n ge ( P GI-C) Q uesti o n n aire .............................. 5 9
6. 3. 7
Si n o -N as al O utc o me Test ( S N O T -2 2)...................................................................... 5 9
6. 4
E arl y Disc o nti n u ati o n fr o m t he St u d y........................................................................... 5 9
6. 5
L ost t o F oll o w U p ............................................................................................................. 6 0
7
S T U D Y D R U G M A N A G E M E N T....................................................................................... 6 1
7. 1
Descri pti o n of St u d y Dr u g ..............................................................................................6 1
7. 1. 1
I n vesti g ati o n al Pr o d uct ............................................................................................. 6 1
7. 1. 2
P ac k a gi n g, S hi p me nt a n d St or a ge ............................................................................ 6 1
7. 2
D ose a n d A d mi nistr ati o n ................................................................................................. 6 1
7. 2. 1
Met h o d of Assi g ni n g S u bject I de ntific ati o n............................................................ 6 1
7. 2. 2
Selecti o n a n d Ti mi n g of D ose a n d A d mi nistr ati o n................................................. 6 2
7. 2. 3
D ose M o dific ati o ns ..................................................................................................... 6 2
7. 3
Bli n di n g a n d U n bli n di n g ................................................................................................. 6 2
7. 4
Tre at me nt C o m pli a nce.................................................................................................... 6 3
7. 5
Destr ucti o n a n d Ret ur n of St u d y Dr u g .......................................................................... 6 3
8
A D V E R S E E V E N T S ............................................................................................................ 6 4
8. 1
Seri o us A d verse E ve nts ................................................................................................... 6 5
8. 1. 1
Defi niti o n of Seri o us A d verse E ve nt ( S A E) .............................................................6 5
8. 1. 2
C ollecti o n a n d Re p orti n g Seri o us A d verse E ve nts .................................................6 7
8. 2
N o n -seri o us A d verse E ve nts............................................................................................6 8
8. 2. 1
C ollecti o n a n d Re p orti n g of N o n -Seri o us A d verse E ve nts ....................................6 8
8. 2. 2
L a b or at or y Test A b n or m alities ................................................................................ 6 8
8. 3
O ver d ose ...........................................................................................................................6 8
8. 4
Pre g n a nc y .........................................................................................................................6 8
8. 5 
P ote nti al Dr u g I n d uce d Li ver I nj ur y ( DI LI) ................................ ................................6 9
8. 6
A d verse E ve nts of S peci al I nterest .................................................................................7 0
8. 7
E n vir o n me nt al E x p os ure, E x p os ure D uri n g Bre astfee di n g, a n d Occ u p ati o n al 
E x p os ure ........................................................................................................................... 7 1
8. 7. 1
E x p os ure D uri n g Bre astfee di n g ................................................................................ 7 1
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
8. 7. 2
Occ u p ati o n al E x p os ure ............................................................................................. 7 1
8. 8
L ac k of Effic ac y ................................................................................................................ 7 2
8. 9
Me dic ati o n Err ors ............................................................................................................ 7 2
9
S T A TI S TI C S ......................................................................................................................... 7 3
9. 1
Ge ner al Pr oce d ures ......................................................................................................... 7 3
9. 2
S a m ple Size ....................................................................................................................... 7 3
9. 3
P o p ul ati o ns f or A n al ysis a n d Esti m a n ds ....................................................................... 7 3
9. 4
St atistic al Met h o ds ........................................................................................................... 7 4
9. 4. 1
De m o gr a p hic a n d B aseli ne C h ar acteristics ............................................................. 7 4
9. 4. 2
Pri m ar y E n d p oi nt(s) .................................................................................................. 7 5
9. 4. 3
Sec o n d ar y E n d p oi nt(s) ..............................................................................................7 5
9. 4. 4
A dj ust me nt f or M ulti plicit y...................................................................................... 7 6
9. 4. 5
Missi n g D at a ............................................................................................................... 7 7
9. 4. 6
Resc ue Me dic ati o n ..................................................................................................... 7 7
9. 4. 7
A n al ysis of S afet y ....................................................................................................... 7 8
9. 5
Sc he d ule of A n al yses ........................................................................................................ 7 8
1 0
E T HI C S A N D R E S P O N SI B I LI TI E S ................................................................................. 7 9
1 0. 1
G o o d Cli nic al Pr actice..................................................................................................... 7 9
1 0. 2
Disse mi n ati o n of Cli nic al St u d y D at a ............................................................................ 8 0
1 0. 3
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee....................................... 8 1
1 0. 4
I nf or me d C o nse nt ............................................................................................................ 8 1
1 0. 5
C ase Re p ort F or ms .......................................................................................................... 8 2
1 0. 6
S p o ns or’s Me dic all y Q u alifie d I n di vi d u al..................................................................... 8 2
1 1
R E C O R D S M A N A G E M E N T ..............................................................................................8 4
1 1. 1
S o urce D oc u me nt ati o n ..................................................................................................... 8 4
1 1. 2
St u d y Files a n d Rec or d Rete nti o n ..................................................................................8 5
1 2
A M E N D M E N T S ................................................................................................................... 8 6
1 3
P U B LI C A TI O N P O LI C Y .................................................................................................... 8 7
1 4
S T U D Y DI S C O N TI N U A TI O N ........................................................................................... 8 8
1 5
D A T A P R O T E C TI O N ......................................................................................................... 8 9
1 6
A P P E N DI C E S ....................................................................................................................... 9 0
1 6. 1
A P P E N DI X I: Str o n g I n hi bit ors a n d Str o n g a n d M o der ate I n d ucers of 
C Y P 3 A 4 Pr otei n ( N ot all- i ncl usi ve) ............................................................................... 9 0
1 6. 2
A P P E N DI X II: E C G Fi n di n gs of P ote nti al Cli nic al C o ncer n .....................................9 2
1 6. 3  
A P P E N DI X III: C o ntr ace pti ve a n d B arrier G ui d a nce................................ ................9 4
1 6. 3. 1
M ale S u bject Re pr o d ucti ve I ncl usi o n Criteri a
.......................................................9 4
1 6. 3. 2
Fe m ale S u bject Re pr o d ucti ve I ncl usi o n Criteri a ....................................................9 4
1 6. 3. 3
W o m a n of C hil d be ari n g P ote nti al ............................................................................ 9 4
1 6. 3. 4
C o ntr ace pti o n Met h o ds................................ .............................................................9 5
1 6. 4
A P P E N DI X I V: Pr ot oc ol A me n d me nt Hist or y .............................................................9 7
1 7
R E F E R E N C E S ...................................................................................................................1 0 3
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
LI S T O F T A B L E S
T a ble 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) Sc he d ule of Assess me nts ........................................ 3 3
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
LI S T O F A B B R E VI A TI O N S
A C S
Ac ute C or o nar y  S yn dr o me
A D H D
Atte nti o n -Deficit/ H y peracti vit y  Dis or der
A E R D
As piri n E xacer bate d Res pirat or y  Disease
A E
A d verse E ve nt
A L T
Ala ni ne A mi n otra nsferase
A S T
As partate A mi n otra nsferase
A V
Atri o ve ntric ular
b p m
Beats Per Mi n ute
B U N
Bl o o d Urea Nitr o ge n
C B D
Ca na bi di ol
C G R P
Calcit o ni n Ge ne Relate d Pe pti de
CI
C o nfi de nce I nter val
C K
Creati ne Ki nase
C M H
C oc hra n -Ma ntel -Hae nszel
C O P D
C hr o nic O bstr ucti ve P ul m o nar y  Disease
C R F
Case Re p ort F or m
C R O
Cli nical Researc h Or ga nizati o n
C R S
C hr o nic R hi n osi n usitis
C R S w N P
C hr o nic R hi n osi n usitis Wit h Nasal P ol y ps
C S R
Cli nical St u d y  Re p ort
C -S S R S
C ol u m bia -S uici de Se verit y  Rati n g Scale
C T
Cli nical Trial
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C TI S
Cli nical Trial I nf or mati o n S y ste m
C Y P
C y t oc hr o me P-4 5 0
D AI D S
Di visi o n of AI D S
DI LI
Dr u g -I n d uce d Li ver I nj ur y
D S M -V
Dia g n ostic a n d Statistical ma n ual of Me ntal Dis or ders, Fift h e diti o n
D S U
Dr u g Safet y U nit
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
E C
Et hics C o m mittee
E C C
E mer ge nc y  C o ntact Car d
E C G
Electr ocar di o gra m
e C R F
Electr o nic Case Re p ort F or m
E D B
E x p os ure D uri n g Breastfee di n g
E D C
Electr o nic Data Ca pt ure
e Diar y
Electr o nic Diar y
E D P
E x p os ure D uri n g Pre g na nc y
E F D
E m br y o -Fetal De vel o p me nt
e G F R
Esti mate d Gl o mer ular Filtrati o n Rate
E O D
E ver y  Ot her Da y
E O T
E n d of Treat me nt
e P R O
Electr o nic Patie nt Re p orte d O utc o mes
e T M F
Electr o nic Trial Master File
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli nical Trials ( E ur o pea n 
Cli nical Trials Data base)
F D A
F o o d a n d Dr u g A d mi nistrati o n
F S H
F ollicle -Sti m ulati n g H or m o ne
G C P
G o o d Cli nical Practice
G G T
Ga m ma -Gl uta m yl  Tra nsferase
G L P
G o o d La b orat or y  Practice
H b A 1c
He m o gl o bi n A 1 C
H C P
Healt hcare Pr o vi der
H D L
Hi g h -De nsit y  Li p o pr otei n
HI V
H u ma n I m m u n o deficie nc y  Vir us
H R
Heart h Rate
H R T
H or m o ne Re place me nt T hera p y
I B
I n vesti gat or’s Br oc h ure
I CF
I nf or me d C o nse nt F or m
I C H
I nter nati o nal C o nfere nce o n Har m o nizati o n of Tec h nical Re q uire me nts 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
f or P har mace uticals f or H u ma n Use
I C H D-3
T he I nter nati o nal Classificati o n of Hea dac he Dis or ders, 3r d e diti o n
I D
I de ntificati o n
I E C
I n de pe n de nt Et hics C o m mittee
I ND
I n vesti gati o nal Ne w Dr u g
I N R
I nter nati o nal N or malize d Rati o
I RB
I nstit uti o nal Re vie w B oar d
I W R S
I nteracti ve We b Res p o nse S yste m
L B B B
Left B u n dle Bra nc h Bl oc k
L D H
Lactate De h y dr o ge nase
L D L
L o w -De nsit y Li p o pr otei n
L F T
Li ver F u ncti o n Test
M A R
Missi n g at Ra n d o m
M D R D
M o dificati o n of Diet i n Re nal Disease
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
m g
Milli gra m
mI T T
M o difie d I nte nt T o Treat
m m
Milli meter
M M R M
Mi xe d M o del Re peate d Meas ures
mi n
Mi n ute
MI
M y ocar dial I nfarcti o n
M QI
Me dicall y  Q ualifie d I n di vi d ual
N O A E L
N o O bser ve d A d verse Effect Le vel
N R S
N u merical Rati n g Scale
N S AI D
N o n - Ster oi dal A nti-I nfla m mat or y Dr u g
O D T
Orall y  Disi nte grati n g Ta blet
P A C L
Pr ot oc ol A d mi nistrati ve C ha n ge Letter
P CI
Perc uta ne o us C or o nar y  I nter ve nti o n
P C P
P he nc y cli di ne
P GI -C
Patie nt Gl o bal I m pressi o n of C ha n ge
P R N
Pr o Re Nata
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
P S S A
Pfizer S A E S u b missi o n Assista nt
P V C
Pre mat ure Ve ntric ular C o ntracti o n
R B C
Re d Bl o o d Cell
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
Q T L
Q ualit y  T olera nce Li mit
S A E
Seri o us A d verse E ve nt
S A P
Statistical A nal y sis Pla n
S G O T
Ser u m Gl uta mic -O xal oacetic Tra nsa mi nase
S G P T
Ser u m Gl uta mic -P y r u vic Tra nsa mi nase
S N O T -2 2
Si n o -Nasal O utc o me Test – 2 2
S R S D
Si n gle Refere nce Safet y D oc u me nt
T Bili
T otal Bilir u bi n
TI A
Tra nsie nt Isc he mic Attac k
T N F -α
T u m or Necr osis Fact or - Al p ha
T N S S
T otal Nasal S y m pt o m Sc ore
T M F
Trial Master File
U L N
U p per Li mit of N or mal
U K
U nite d Ki n g d o m
U S
U nite d States
W B C
W hite Bl o o d Cell
W O C B P
W o me n of C hil d -Beari n g P ote ntial
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1
I N T R O D U C TI O N A N D R A T I O N AL E
1. 1
B a c k gr o u n d
C hr o nic r hi n osi n usitis ( C R S) is a n i nfla m mat or y disease of t he para nasal si n uses a n d nasal 
ca vit y lasti n g m ore t ha n 1 2 wee ks. Br oa dly, it ca n be di vi de d i nt o t w o p he n ot y pes, C R S wit h a n d 
wit h o ut nasal p ol y ps, wit h a p pr o xi matel y  2 0 % of patie nts ha vi n g nasal p ol yp osis. 6
It is esti mate d t hat C R S affects bet wee n 5-1 2 % of t he ge neral p o p ulati o n, h o we ver, w he n t his is 
c o m bi ne d wit h d oc u me nte d i nfla m mati o n, t he pre vale nce is re d uce d t o 3 -6 %. I t pre d o mi na ntly 
affects t he a d ult p o p ulati o n a n d has si g nifica nt i m pact o n t he q ualit y of life. C R S is c o nsi dere d 
o ne of t he t o p 1 0 m ost c ostl y  healt h c o n diti o ns i n t he U S wit h estimate d i n direct c osts e xcee di n g 
$ 2 2 billi o n per y ear. 7
T he e xact u n derl yi n g mec ha nis ms i n C R S pat h o p h y si ol o g y are u n k n o w n a n d are m ost li kel y 
m ultifact orial. T he disease is belie ve d t o arise fr o m c hr o nic i nfla m mat i o n of t he nasal ca vit y a n d 
para nasal si n uses. Pre dis p osi n g fact ors i ncl u de e n vir o n me ntal (e. g, p oll uti o n, aller ge ns, vir uses, 
bacteria), s ys te mic (e. g., ge netic, c ystic fi br osis, ciliar y defects), a n d l ocal (e. g., a nat o mic, 
p ol y ps, t u m ors) fact ors. 8 C R S is ofte n acc o m pa nie d b y  ot her m or bi dities, s uc h as aller gic
r hi nitis, ast h ma, a n d as piri n e xacer bate d res pirat or y disease ( A E R D).3 ,9
T he dia g n osis re q uires prese nce of at least t w o of t he f o ur car di nal s y m pt o ms (i.e., facial 
pai n/ press ure/f ull ness, nasal o bstr ucti o n (c o n gesti o n), nasal disc har ge, decrease d se nse of s mell) 
a n d c o nfir me d prese nce of i nfla m mati o n b y  ra di o gra p hic i ma gi n g or nasal e n d osc o p y.1 Car di nal 
s ym pt o ms var y  i n pre vale nce, wit h nasal o bstr ucti o n or c o n gesti o n re p orte d as t he m ost c o m m o n 
i n b ot h patie nts wit h or wit h o ut nasal p ol yps. 7
T he g oal of treat me n t is t o re d uce t he i nfla m mati o n, rest ore m uc ociliar y cleara nce a n d si n us 
drai na ge, a n d pre ve nt i nfecti o ns. 8 T he first -li ne treat me nt t ypicall y  i ncl u des t o pical i ntra nasal 
ster oi ds a n d nasal sali ne irri gati o n, h o we ver, t he efficac y is li mite d. M ore effecti ve t hera pies 
i ncl u de s yste mic c ortic oster oi ds a n d l o n g-ter m a nti bi otics, t h o u g h t he y are ass ociate d wit h 
si g nifica nt si de effects.4 ,5 O ne st u d y  f o u n d t hat i n patie nts wit h C R S w N P a n d se veral oral 
c ortic oster oi d b ursts per year, 4 3 % of patie nts de vel o pe d oste o p or osis a n d 4 9 % de vel o pe d
seco n dar y  a dre nal i ns ufficie nc y.1 0 A p pr o xi matel y  half of t he C R S patie nts will e ve nt uall y 
u n der g o e n d osc o pic s ur ger y  i n or der t o c o ntr ol t heir s ym pt o ms, h o we ver, t he maj orit y  will still 
ha ve i na de q uate s y m pt o m relief a n d ~ 3 7 % will nee d at least o ne re visi o n s ur ger y.2 ,4
B H V -3 0 0 0 ( P F-0 7 8 9 9 8 0 1) (ri me ge pa nt) is a calcit o ni n ge ne-relate d pe pti de ( C G R P) rece pt or 
a nta g o nist i n de vel o p me nt f or t he ac ute treat me nt of C R S. T he C G R P rece pt or i s l ocate d wit hi n 
pai n -si g nali n g pat h wa ys, i ntracra nial arteries a n d t he tri ge mi nal ga n gli o n, a n d its acti vati o n is 
t h o u g ht t o pla y a ca usal r ole i n C R S pat h o p h ysi ol o g y. 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Treat me nt wit h a C G R P rece pt or a nta g o nist is belie ve d t o e xert m ulti ple d o w nstrea m eff ects t hat 
ma y  pr o vi de be nefits i n treat me nt of C R S t hr o u g h t he f oll o wi n g p ossi ble mec ha nis ms:
Bl oc ki n g Ne ur o ge nic I nfl a m m ati o n : Bi n di n g of C G R P rece pt or a nta g o nists t o C G R P rece pt ors 
l ocate d o n satellite glial cells w o ul d i n hi bit i nfla m mati o n ca use d by tri ge mi nal ner ve release of 
C G R P o nt o satellite glial cells a n d cell b o dies of a- delta fi bers i n t he tri ge mi nal ga n gli o n.
Decre asi n g Arter y Dil ati o n : B y bl oc ki n g t he C G R P rece pt ors l ocate d i n s m o ot h m uscle cells 
wit hi n vessel walls, C G R P rece pt or a nta g o nists w o ul d i n hi bit t he pat h ol o gic dilati o n of arteries 
wit h o ut t he u n wa nte d effect of acti ve vas oc o nstricti o n.
I n hi biti n g P ai n Tr a ns missi o n: Bi n di n g of C G R P rece pt or a nta g o nists t o C G R P rece pt ors 
w o ul d s u p press t he tra ns missi o n of pai n b y  i n hi biti n g t he ce ntral rela y of pai n si g nals fr o m t he 
tri ge mi nal ner ve t o t he ca u dal tri ge mi nal n ucle us.
1. 2
Pr o d u ct D e v el o p m e nt B a c k gr o u n d
Details of t he cli nical a n d precli nical st u dies are pr o vi de d i n t he m ost c urre nt I n vesti gat or 
Br oc h ure. A s u m mar y  of t he rele va nt data t o t he st u d y are prese nte d bel o w.
Ri me ge pa nt is a p pr o ve d f or t he ac ute treat me nt a n d pre ve nti o n of e pis o dic mi grai ne i n t he 
U nite d S tates ( U S), Unite d K i n g d o m ( U K), a n d E ur o pea n U ni o n ( E U) a n d is well t olerate d i n 
h u ma ns w he n gi ve n as a si n gle oral d ose of 7 5 m g f or t he ac ute treat me nt of mi grai ne a n d at a 
d ose of 7 5 m g e ver y ot her da y (E O D ) f or t he pre ve nti o n of e pis o dic mi grai ne. T he efficac y , 
safety, a n d t olera bilit y of ri me ge pa nt f or t he ac ute a n d pre ve nti ve treat me nt of mi grai ne i n t he 
pe diatric p o p ulati o n is c urre ntl y bei n g e val uate d.
As of 2 6 A u g ust 2 0 2 2, m ore t ha n 8 9 0 0 u ni q ue s u bjects ha ve partici pate d i n P hase 1 st u dies i n 
healt h y  s u bjects or P hase 2 a n d 3 st u dies i n s u bjects wit h mi grai ne or refract or y tri ge mi nal 
ne ural gia, chr o nic r hi n osi n usitis , or te mp or o ma n di b ular dis or ders ; of t hese, a p pr o xi matel y 6 0 3 6 
u ni q ue s u bjects ha ve recei ve d ri me ge pa nt at a n y d ose. C ollecti vel y , t he c urre nt data 
de m o nstrates a fa v ora ble be nefit-ris k pr ofile f or ri me ge pa nt i n t he ac ute a n d pre ve nti ve treat me nt 
of mi grai ne .
Please refer t o t he m ost u p -t o- date I n vesti gat or’s Br oc h ure f or a d diti o nal i nf or mati o n.
1. 3
St u d y R ati o n al e
C hr o nic r hi n osi n usitis ( C R S) is a s y m pt o matic i nfla m mati o n of t he para nasal si n uses a n d nasal 
ca vit y lasti n g m ore t ha n 1 2 wee ks. T y picall y , it ma nifest s as facial pai n/ press ure/f ull ness, nasal 
o bstr ucti o n (c o n gesti o n), nasal disc har ge, a n d/ or decrease d se nse of s mell. 1- 3
T he nasal ca vit y  a n d para nasal si n uses recei ve sens or y  a n d n ocice pti ve i n ner vati o n fr o m distal 
bra nc hes of t he tri ge mi nal ner ve. Alt h o u g h t he u n derl yi n g mec ha nis ms of C R S ha ve n ot bee n 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
f ull y el uci date d, n u mer o us st u dies ha ve i m plicate d tri ge mi nal ner ve a n d C G R P i n t he 
pat h o p h y si ol o g y of t he disease a n d su g geste d t hera pe utic be nefits of C G R P a nta g o nis m. C G R P + 
fi bers are pre d o mi na ntly f o u n d i n t he ma xillar y si n uses a n d t o lesser e xte nt i n ot her si n uses.
Pre vi o us st u dies ha ve s u g geste d t hat C G R P c o nt ri b utes t o nasal secreti o n b y i n d uci n g s ustai ne d 
arterial vas o dilati o n, i ncreasi n g nasal bl o o d fl o w, a n d p ossi bl y  b y i ncreasi n g plas ma fl u x acr oss 
fe nestrate d ca pillaries.1 3 - 1 8 I n a cli nical st u d y, i ntra nasal a d mi nistrati o n of C G R P i n healt h y 
v ol u nteers res ulte d i n i ncreases i n bl o o d fl o w, t he se nsati o ns of o bstr ucti o n, hea dac he, a n d mil d 
s neezi n g.1 3
A n ot her st u d y f o u n d t hat in patie nts wit h c hr o nic r hi n osi n usitis, nasal m uc osa C G R P le vels 
c orrelated wit h s y m pt o m i nte nsit y  a n d t he n u m ber of i nfla m mat or y cells.1 9 M ore o ver,
i n a st u d y
wit h aller gic r hi n osi n usitis, t he baseli ne sali var y C G R P le vels were ele vate d i n bet wee n 
attac ks. 2 0 Intra nasal ca psaici n a p plicati o n has bee n s h o w n t o re d uce p ol y p rec urre nce f oll o wi n g 
s ur ger y a n d decrease t he i nte nsit y of nasal o bstr ucti o n i n C R S .2 1 I n a precli nical st u d y i n pi g 
nasal m uc osa, C G R P a nta g o nists atte n uate d ca psaici n- , hista mi ne-, a n d bra d yki ni n -i n d uce d 
vas o dilati o n. 2 2 I n a n ot her st u d y, C G R P 8 -3 7 atte n uate d t he ca psaici n -i n d uce d vas o dilati o n a n d 
decrease i n nasal ca vit y v ol u me w hi c h was u naffecte d b y N K 1 -a nta g o nists. T his s u g gests t hat 
C G R P, b ut n ot s u bsta nce P, is a n i m p orta nt me diat or of nasal vasc ular c ha n ges res ulti n g fr o m 
acti vati o n of C-fi ber affere nts.2 3
B H V - 3 0 0 0 ( P F-0 7 8 9 9 8 0 1) (ri me ge pa nt) is a calcit o ni n ge ne-relate d pe pti de ( C G R P) rece pt or 
a nta g o nist i n de vel o p me nt f or t he ac ute treat me nt of C R S . T he C G R P rece pt or is l ocate d wit hi n 
pai n -si g nali n g pat h wa ys, i ntracra nial arteries a n d t he tri ge mi nal ga n gli o n, a n d its acti vati o n is 
t h o u g ht t o pla y a ca usal r ole i n C R S pat h o p h y si ol o g y. 
T his st u d y  is bei n g c o n d ucte d t o e val uate t he efficac y, safety, a n d t olera bilit y  of ri me ge pa nt f or 
t he ac ute treat me nt of C R S . It will als o f urt her defi ne t he safet y pr ofile of ri me ge pa nt 
a d mi nistrati o n i n t his patie nt p o p ulati o n, se paratel y fr o m t he a p pr o ve d i n dicati o n of ac ute a n d 
pre ve nti ve treat me nt of mi grai ne.
1. 3. 1
St u d y D e si g n R ati o n al e
T his is a d o u ble - bli n d, ra n d o mize d, m ultice nter, o ut patie nt e val uati o n of t he safety a n d efficac y 
of ri me ge pa nt as c o m pare d t o place b o i n t he ac ute treat me nt of c hr o nic r hi n osi n usitis ( C R S) wit h 
or wit h o ut p ol y ps . T he st u d y dr u g will be ri me ge pa nt f or m ulate d i n a 7 5 m g O D T (place d o n or 
u n der t he t o n g ue ) or a matc hi n g place b o. T he s u bjects will be i nstr ucte d t o ta ke t heir st u d y 
me dicati o n, as a n o ut patie nt, w he n (if) t he y  ha ve a facial pai n/ press ure/f ull ness w hic h reac hes 
i nte nsit y of ≥6 o n t he N R S ( 0 -1 0). 
T he st u d y  will ra n d o mize a p pr o xi matel y 2 8 6 s u bjects t o res ult i n a p pr o xi matel y 2 0 0 e val ua ble 
s u bjects. T he s u bjects will be ra n d o mize d i n a 1: 1 rati o t o t he ri me ge pa nt or place b o treat me nt 
gr o u ps. T he ra n d o mizati o n will be stratifie d b y  t he prese nce of nasal p oly p s ( yes or n o).
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1. 3. 2
D o s e S el e cti o n R ati o n al e
T he P hase 2 b d ose -ra n gi n g st u dy, C N 1 7 0 0 0 3 , esta blis he d t hat ri me ge pa nt 7 5 m g is t he mi ni m u m 
effecti ve d ose f or t he ac ute treat me nt of mi grai ne. T he t hree P hase 3 st u dies , B H V 3 0 0 0 - 3 0 1, 
B H V 3 0 0 0 -3 0 2, a n d B H V 3 0 0 0 - 3 0 3, c o nfir me d t his efficac y usi n g t he c urre nt re gistrati o nal 
e n d p oi nts f or ac ute treat me nt of mi grai ne. T his o bser vati o n a n d t he flat d ose- res p o nse wit h 
ri me ge pa nt a n d ot her C G R P rece pt or a nta g o nists s u g gest t hat ri me ge pa nt 7 5 m g ma y be a n 
effecti ve d ose f or t he ac ute treat me nt of c hr o nic r hi n osi n usitis wit h or wit h o ut p ol yps . T he 
p har mac o ki netic pr ofile of ri me ge pa nt s u p p orts t his st u d y’s a d mi nistrati o n of a si n gle d ose.
Please refer t o t he c urre nt versi o n of I n vesti gat or’ s Br oc h ure f or a s u m mar y of t he cli nical safety 
pr ofile.
1. 3. 3
R e s e ar c h H y p ot h e si s
Ri me ge pa nt will ha ve efficac y s u peri or t o place b o i n t he ac ute treat me nt of c hr o nic 
r hi n osi n usitis ( C R S) wit h or wit h o ut p ol y ps wit h a fa v ora ble safet y  pr ofile.
1. 3. 4
B e n efit/ Ri s k
Ri me ge pa nt re prese nts a n a d va nce me nt i n mi grai ne t hera pe utics, pr o vi di n g t he first C G R P 
a nta g o nist t o de m o nstr ate be nefit f or b ot h t he ac ute treat me nt a n d pr o p h yl a xis of mi grai ne.
Ri me ge pa nt a p pears t o be ge nerall y safe a n d well t olerate d i n h u ma ns w he n gi ve n as si n gle oral 
d oses fr o m 7 5 m g u p t o t he ma xi m u m d ose of 1 5 0 0 m g a n d m ulti ple oral d oses u p t o t he 
ma xi m u m dail y  d ose of 6 0 0 m g f or 1 4 da ys. 
Br oa d a n d s ustai ne d efficac y of ri me ge pa nt 7 5 m g was de m o nstrate d i n 3 pre vi o usl y  c o m plete d 
P hase 3 st u dies ( B H V 3 0 0 0 -3 0 1, B H V 3 0 0 0 - 3 0 2, a n d B H V 3 0 0 0 -3 0 3). Statisticall y  si g nifica nt 
efficac y was de m o nstrate d o n t he c o-pri m ar y e n d p oi nts of free d o m fr o m pai n, a n d free d o m fr o m 
m ost b ot hers o me s y m pt o m at 2 h o urs p ost -d ose. Si milar res ults were de m o nstrate d i n t he 
B H V 3 0 0 0 -3 1 0 st u d y  rece ntl y c o m plete d i n C hi na a n d K orea. I n t he P hase 2/ 3 place b o-c o ntr olle d 
st u d y ( B H V 3 0 0 0-3 0 5) f or t he pre ve nti ve treat me nt of mi grai ne, ri me ge pa nt at a d ose of 7 5 m g 
e ver y ot her da y ( E O D) de m o nstrate d statisticall y si g nifica nt s u peri orit y t o place b o o n t he 
pri mar y  e n d p oi nt of c ha n ge fr o m t he o bser vati o n peri o d i n t he mea n n u m ber of mi grai ne da ys 
per m o nt h o n treat me nt i n t he last m o nt h of t he d o u ble - bli n d treat me nt p hase.
A m ultice nter o pe n -la bel, l o n g-ter m st u d y ( B H V 3 0 0 0-2 0 1) was c o n d ucte d t o e val uate t he safet y 
a n d t olera bilit y of ri me ge pa nt 7 5 m g ta blet ta ke n as nee de d ( u p t o o ne ta blet per da y u p o n o nset 
of a mi grai ne of mil d, m o derate, or se vere i nte nsit y ) f or t he ac ute treat me nt of mi grai ne f or u p t o 
5 2 wee ks. T his m ulti ple -d ose, l o n g -ter m st u d y of ri me ge pa nt 7 5 m g a d mi nistere d f or u p t o 5 2 
wee ks c o nfir me d t he fa v ora ble safet y pr ofile acr oss a var iety of safet y e n d p oi nts, i ncl u di n g A E 
assess me nts, cli nical la b orat or y  testi n g i ncl u di n g li ver f u ncti o n tests (L F Ts ), vital si g ns a n d 
electr ocar di o gra ms ( E C Gs) . Safety data fr o m t he d o u ble - bli n d treat me nt a n d t he o pe n-la bel 
e xte nsi o n p hases of t he pi v otal P hase 2/ 3, ra n d o mize d, d o u ble- bli n d, place b o -c o ntr olle d 
pre ve nti ve treat me nt of mi grai ne st u d y ( B H V 3 0 0 0 -3 0 5) s u p p ort a fa v ora ble safet y pr ofile of 
ri me ge pa nt 7 5 m g a d mi nistere d E O D f or t he pre ve nti ve treat me nt of mi grai ne. Ri me ge pa nt 7 5 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
m g a d mi nistere d E O D + P R N f or u p t o 5 2 wee ks i n t he o pe n- la bel p hase is well t olerate d, wit h 
n o ne w safet y  si g nals o bser ve d i n t he o pe n-la bel-e xte nsi o n p hase.
Acr oss ri me ge pa nt cli nical de vel o p me nt pr o gra m, l o w fre q ue nc y  of e ve nts of h yperse nsiti vit y  
(i ncl u di n g urticaria, an gi oe de ma, a na p h yl actic reacti o n a n d ras h) were o bser ve d. N o A Es 
re prese nti n g seri o us c uta ne o us ma nifestati o n of h y perse nsiti vit y (e. g., Ste ve ns -J o h ns o n 
s yn dr o me) were o bser ve d.
Acr oss t he ri me ge pa nt cli nical de vel o p me nt pr o gra m, n o cases of H y ’s La w were i de ntifie d, a n d
t here was n o si g nal of DI LI d ue t o ri me ge pa nt w he n a d mi nistere d u p t o o nce daily P R N f or u p t o
5 2 wee ks of treat me nt.
T here are n o a de q uate data o n t he de vel o p me ntal ris k ass ociate d wit h t he use of ri me ge pa nt i n 
pre g na nt w o me n. B ot h w o me n of c hil d beari n g p ote ntial, as well as t h ose w h o are of 
n o n- c hil d beari n g p ote ntial, ma y be e nr olle d gi ve n t he a vaila bilit y of e m br y o-fetal de vel o p me nt
(E F D ) n o ncli nical t o xicit y  st u dies wit h ri me ge pa nt. C o ntrace pti o n met h o d is re q uire d, a n d 
meas ures will be ta ke n t o li mit t he ris k of pre g na nc y i n t he fe male p o p ulati o n of c hil d beari n g 
p ote ntial e nr olle d ( See Secti o n 1 6. 3 ). T he p ote ntial ris k of e x p os ure t o ri me ge pa nt i n a se x ual 
part ner of a male s u bjects i n t his st u d y via ejac ulate is l o w, a n d t heref ore n o c o ntrace pti o n 
(c o n d o m) use i n male s u bjects is warra nte d. T he calc ulate d safety mar gi n is ≥1 0 0- f ol d bet wee n 
t he esti mate d part ner e x p os ure d ue t o se mi nal tra nsfer a n d t he N O A E L f or seri o us ma nifestati o ns 
of de vel o p me ntal t o xicit y  i n n o ncli nical st u dies. T he safety mar gi n of 1 0 0 -f ol d is base d o n 
a p pl yi n g a 1 0-f ol d safety fact or f or i nters pecies e xtra p olati o n a n d a 1 0 -f ol d safety fact or f or 
s usce pti ble p o p ulati o ns. 2 8
S u bjects u n der g o re g ular pre g na nc y  testi n g t hr o u g h o ut t he d urati o n of t he st u d y. Alt h o u g h n o 
safety iss ues i n cli nical trials of ri me ge pa nt were o bser ve d, car di o v asc ular e ve nts, 
cere br o vasc ular e ve nts, h y perte nsi ve e ve nts, a n d seri o us gastr oi ntesti nal e ve nts ass ociate d wit h 
c o nsti pati o n are re vie we d i n eac h a g gre gate re p ort per T he U nite d States F o o d a n d Dr u g 
A d mi nistrati o n ( F D A ) re q uest. N o ne of t hese re vie ws ha ve detecte d a n y  safet y si g nal ass ociate d 
wit h t hese e ve nts. S u bjects are e xcl u de d if t here is u nc o ntr olle d, u nsta ble, or rece ntl y  dia g n ose d 
car di o vasc ular disease or h y perte nsi o n. S u bjects are m o nit ore d t hr o u g h m ulti ple safet y  
e n d p oi nts, i ncl u di n g A E assess m e nts, cli nical la b orat or y testi n g, vital si g ns a n d E C Gs.
Re vie w of all data a vaila ble, i ncl u di n g p ost -mar keti n g i nf or mati o n, n o ncli nical, cli nical, a n d 
scie ntific literat ure data, de m o nstrates a fa v ora ble be nefit-ris k pr ofile f or t he use of ri me ge pa nt 
i n this st u d y . M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d 
reas o na bly e x pecte d A E s of ri me ge pa nt m a y  be f o u n d i n t he I nvesti gat or Br oc h ure , w hic h is t he 
S R S D f or t his st u d y . 
I n vesti gat ors are t o m o nit or c ha n ges i n he mat ol o g y, c he mistr y, a n d ot her la b orat or y meas ures 
(see Secti o n 8. 5 ). I n a d diti o n, In vesti gat ors are re q uire d t o m o nit or all re p orte d A Es, c ha n ges o n 
p h y sical e xa mi nati o n, E C G, a n d e mer ge nt la b a b n or malities, etc. (see Ta b le 1).
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 2 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
2
S T U D Y O B J E C TI V E S
2. 1
Pri m ar y O bj e cti v e( s)
T o e val uate t he efficac y  of ri me ge pa nt c o m pare d wit h place b o i n t he ac ute treat me nt of chr o nic 
r hi n osi n usitis wit h o r wit h o ut p ol y ps o n mea n c ha n ge fr o m baseli ne of facial
pai n/ press ure/f ull ness o n N R S ( 0 -1 0) sc ore at 2 h o urs p ost d ose .
2. 2
S e c o n d ar y O bj e cti v e( s)
1.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n T otal Nasal 
S y m pt o m Sc ore ( T N S S) at 2 h o urs p ost -d ose.
2.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n nasal o bstr ucti o n
(c o n gesti o n) sc ore o n N R S ( 0-1 0) sc ore at 2 h o urs p ost -d ose.
3.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne i n nasal disc har ge
sc ore o n N R S ( 0-1 0) s c ore at 2 h o urs p ost -d ose.
4.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n hea dac he pai n relief o n a 4 -p oi nt Li kert
scale at 2 h o urs p ost -d ose c o m pare d t o baseli ne.
5.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he pr o ba bilit y of re q uiri n g resc ue 
me dicati o n wit hi n 2 4 h o urs of i nitial treat me nt.
2. 3
E x pl or at or y  O bj e cti v e( s) 
1.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 3 0 % re d ucti o n fr o m baseli ne of facial
pai n/ press ure/f ull ness N R S ( 0- 1 0) sc ore at 2 h o urs.
2.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 5 0 % re d ucti o n fr o m baseli ne of facial
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 2 h o urs.
3.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne of facial
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 
h o urs p ost -d ose.
4.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne of nasal 
o bstr ucti o n (c o n gesti o n) N R S ( 0 - 1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 
h o urs p ost -d ose.
5.
T o e val uate t he effect of ri me ge p a nt c o m pare d t o place b o o n c ha n ge fr o m baseli ne of nasal 
disc har ge N R S ( 0 -1 0) sc ore at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs p ost -d ose.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6.
T o e val uate t he effect of ri me ge pa nt c o m pare d t o place b o o n hea dac he pai n relief usi n g a 4 -
p oi nt Li kert scale at 1 5, 3 0, 4 5, 6 0, 9 0 mi n utes a n d 2, 4, 8 a n d 2 4 h o urs p ost- d ose c o m pare d 
t o baseli ne.
7.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he P GI- C q uesti o n naire at 2 4 h o urs p ost-
d ose.
8.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 3 0 % re d ucti o n fr o m baseli ne of facial 
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 2 4 h o urs.
9.
T o e val uate ri me ge pa nt c o m pare d t o place b o o n ≥ 5 0 % re d ucti o n fr o m baseli ne of facial 
pai n/ press ure/f ull ness N R S ( 0 -1 0) sc ore at 2 4 h o urs.
1 0. T o e val uate ri me ge pa nt c o m pare d t o place b o o n s ustai ne d relief of facial 
pai n/ press ure/f ull ness, as defi ne d b y eac h of t he f oll o wi n g: 3 0 % re d ucti o n fr o m baseli ne o n 
N R S ( 0 -1 0), 1. 5 -p oi nt re d ucti o n o n N R S ( 0 - 1 0), a n d a 2-p oi nt re d ucti o n o n N R S ( 0 -1 0) 
t hr o u g h 2 4 h o urs p ost-d ose.
1 1. T o e x pl ore t he distri b uti o n of baseli ne disease se verit y usi n g t he of Si n o -Nasal O utc o me Test 
( S N O T-2 2).
1 2. T o e val uate ri me ge pa nt c o m pare d t o place b o o n t he Si n o -Nasal O utc o me Test ( S N O T -2 2) 
sc ore at 2 4 h o urs p ost-d ose.
1 3. T o e val uate t he safet y a n d t olera bilit y of ri me ge pa nt i n t he acute treat me nt of c hr o nic 
r hi n osi n usitis as meas ure d b y t he fre q ue nc y of a d verse e ve nts of m o derate or se vere 
i nte nsit y, seri o us a d verse e ve nts ( S A Es), cli nically rele va nt la b orat or y a b n or malities, a n d 
nasal i ns pecti o n a b n or malities.
1 4. T o e val uate ri me ge pa nt c o m pare d t o place b o f or t he C ol u m bia -S uici d e Se verit y  Rati n g Scale 
( C-S S R S).
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
3 
S T U D Y E N D P OI N T S 
3. 1
Pri m ar y E n d p oi nt( s)
C ha n ge fr o m baseli ne facial pai n/ press ure/f ull ness will be assesse d usi n g t he n u m ber of 
e val ua ble s u bjects t hat re p ort facial pai n/ press ure/f ull ness ≥6 o n N R S ( 0 -1 0) at baseli ne a n d 
w h o als o re p ort pai n le vel at 2 h o urs p ost -d ose rec or de d i n t he e Diar y.
3. 2
S e c o n d ar y E n d p oi nt( s)
1.
C ha n ge fr o m baseli ne of T ot al N as al S y m pt o m Sc ore ( T N S S) will be assesse d usi n g t he 
n u m ber of e val ua ble s u bjects t hat re p ort facial pai n/ press ure/f ull ness, nasal o bstr ucti o n
(c o n gesti o n), a n d nasal disc har ge sc ores at baseli ne a n d at 2 h o urs p ost -d ose i n t he e Diar y.
2.
C ha n ge fr o m baseli ne of n as al o bstr ucti o n (c o n gesti o n ) will be assesse d usi n g t he n u m ber 
of e val ua ble s u bjects t hat re p ort nasal o bstr ucti o n (c o n gesti o n) sc ore o n N R S ( 0 -1 0) sc ore at 
baseli ne a n d 2 h o urs p ost -d ose i n t he e Diar y.
3.
C ha n ge fr o m baseli ne of n as al disc h ar ge will be assesse d usi n g t he n u m ber of e val ua ble 
s u bjects t hat re p ort nasal disc har ge sc ore o n N R S ( 0 -1 0) sc ore at baseli ne a n d 2 h o urs p ost -
d ose i n t he e Diar y.
4.
H e a d ac he p ai n relief will be assesse d usi n g t he n u m ber of e val ua ble s u bjects t hat re p ort a 
hea dac he pai n le vel of m o derate or s e vere i nte nsit y at baseli ne a n d t he n re p o rt a pai n le vel of 
n o ne or mil d at 2 h o urs p ost -d ose i n t he e Diar y usi n g a 4 -p oi nt L i kert scale.
5.
T he pr o b a bilit y of re q uiri n g resc ue me dic ati o n will be assesse d usi n g t he n u m ber of 
s u bjects t hat ta ke resc ue me dicati o n wit hi n 2 4 h o urs after a d mi nistrati o n of st u d y  me dicati o n 
(ri me ge pa nt or place b o).
3. 3
M e a s ur e s of i nt er e st
Safet y  a n d Ot her assess me nts:

A d verse E ve nts

E C G assess me nts

Vital Si g n s a n d P h y sical Meas ure me nts

R o uti ne L a b orat or y Tests

C ol u m bia -S uici de Se verit y  Rati n g Scale ( C-S S R S) 

Assess me nt of C R S Pai n a n d S y m pt o ms

Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI -C)

Si n o -Nasal O utc o me Test ( S N O T - 2 2)
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
4
S T U D Y P L A N
4. 1
St u d y D e si g n a n d D ur ati o n
T his is a d o u ble - bli n d, ra n d o mize d, m ultice nter, o ut patie nt e val uati o n of t he safety a n d efficac y 
of ri me ge pa nt as c o m pare d t o place b o i n t he ac ute treat me nt of c hr o nic r hi n osi n usitis wit h or 
wit h o ut p ol y ps . S u bjects will be dis pe nse d o ne d ose of st u d y me dicati o n c o nsisti n g of a 
ri me ge pa nt 7 5 m g O D T (place d o n or u n der t he t o n g ue ) or a matc hi n g place b o. T he t otal 
d urati o n of s u bject’s st u d y partici pati o n will be u p t o a p pr o xi matel y 6 6 da ys. T his i ncl u des a 3 t o 
1 4 da y  ( + 2 da ys f or sc he d uli n g p ur p oses, if nee de d) Scree ni n g Peri o d, a n Ac ute Treat me nt P hase 
t hat ca n last u p t o 4 5 da ys or u ntil t he s u bject has a facial pai n / press ure/f ull ness t hat reac hes a 
c urre nt i nte nsity of ≥6 o n t he N R S ( 0 -1 0), f oll o we d b y  a n E n d of Treat me nt Visit ( E O T) wit hi n
7 da y s ( + 2 d a y s f or sc he d uli n g p ur p oses, if nee de d) after t he a d mi nistrati o n of t he st u d y  
me dicati o n .
If a s u bject has N O T e x perie nce d a facial pai n/ press ure/f ull ness of s ufficie nt se verit y wit hi n 4 5 
da y s after ra n d o mizati o n, t he y still are re q uire d t o c o m plete all EO T visit pr oce d ures. 
All s u bjects m ust ret ur n e m pt y me dicati o n c o ntai ners or u n use d st u d y  me dicati o n a n d t he e Diar y 
t o t he st u d y ce nter.
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last s u bject.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
4. 2
S c h e d ul e of A s s e s s m e nt s
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
Eli gi bilit y Assess m e nts
I nf or me d 
C o nse nt
X
I ncl usi o n/ 
E xcl usi o n 
Criteria
X
X
Me dical Hist or y
X
C ollect Dail y 
Use of 
Me dicati o ns t o 
Re d uce 
I nte nsit y of 
C R S S y m pt o ms 
/ C o nc o mita nt 
Me dicati o ns
X
X
X
S u bjects will be 
gi ve n pa per diaries t o 
use t o kee p trac k of 
t heir c o nc o mita nt 
me dicati o ns a n d 
resc ue me dicati o ns 
t hr o u g h o ut t he st u d y. 
All me dicati o ns 
ta ke n f or a n y reas o n 
s h o ul d be 
d oc u me nte d.  Site 
staff s h o ul d i nstr uct 
s u bjects o n pr o per 
use of t he pa per 
diaries a n d i nstr uct 
s u bjects t hat t he 
diaries will be 
c ollecte d, re vie we d, 
a n d disc usse d wit h 
t he s u bject at eac h 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
visit.
Ass ess me nt of 
C R S Hist or y)
X
P a per s o urce 
d oc u me nt will be 
use d t o ca pt ure C R S 
Hist or y a n d e ntere d 
i n e C R F
S afet y Assess me nts
P h ysical 
E xa mi nati o n
X
X
Vital 
Si g ns/ P h ysical 
Meas ure me nts
X
X
X
Vital Si g ns c o nsist of 
sitti n g arterial 
s yst olic a n d diast olic 
bl o o d press ure, heart 
rate, oral b o d y 
te m perat ure, b o d y 
wei g ht a n d hei g ht.  
Hei g ht a n d wei g ht 
will o nl y be 
meas ure d at 
Scree ni n g.
Cli nical Safet y 
La b orat or y 
Testi n g
X
X
All Scree ni n g visit
la b orat or y test res ults 
m ust be recei ve d 
pri or t o Baseli ne 
Visit (ra n d o mizati o n)
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
F S H
X
F S H le vels will be 
meas ure d o n p ost -
me n o pa usal w o me n 
t o c o nfir m p ost-
me n o pa usal stat us. 
F S H le vel testi n g is 
n ot re q uire d f or 
w o me n greater t ha n 
or e q ual t o 6 2 years 
ol d wit h a me n orr hea 
of greater t ha n or 
e q ual t o 1 year.
H b A 1c
X
Li pi d Pa nel
X
Tri gl yceri des, t otal 
c h olester ol, H D L, 
a n d L D L
Uri ne dr u g 
scree n f or dr u gs 
of a b use
X
X
E C G
X
X
Pre g na nc y Test
X
X
X
X
A ser u m pre g na nc y 
test will be 
c o m plete d at 
Scree ni n g a n d E n d of 
Treat me nt Visits as 
part of t he sta n dar d 
la b orat or y tests (if 
a p pr o priate). 
C o nfir mat or y uri ne 
pre g na nc y test f or 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
W O C B P s h o ul d be 
c o m plete d o n site at 
t he Baseli ne Visit 
a n d a n y s u bse q ue nt 
visits f or 
c o nfir mati o n at t he 
I n vesti gat or’s 
discreti o n. H o me 
pre g na nc y test will 
be pr o vi de d t o 
W O C B P after 
c o m pleti o n of 
baseli ne visit. 
W O C B P s u bjects 
m ust c o m plete t he 
uri ne pre g na nc y test 
at h o me, a n d t hat test 
res ult m ust be 
ne gati ve pri or t o 
ta ki n g st u d y 
me dicati o n.
A d verse E ve nt 
a n d Seri o us 
A d verse E ve nt 
Assess me nt
X
X
X
X
X
X
X
S A Es a n d n o n -
seri o us AEs are 
re p orte d fr o m t he 
ti me of i nf or me d 
c o nse nt. See Secti o n
8 of t he pr ot oc ol f or 
f urt her i nf or mati o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
C ol u m bia -
S uici de 
Se verit y Rati n g 
Scale ( C -S S R S)
X
X
X
T his scale will be 
cli nicia n 
a d mi nistere d, 
c o m plete d o n site, 
a n d will be i n pa per. 
T he s o urce d oc u me nt 
will be pr o vi de d b y 
Pf izer. See Secti o n 
6. 2. 5 f or f urt her 
details.  
Cli nic al Dr u g S u p plies/ St u d y S u p plies
Ra n d o mize
X
S u bjects will be 
ra n d o mize d i n t he 
I W R S s yste m at t he 
Baseli ne Visit 
(ra n d o mizati o n)
Dis pe nse St u d y 
Me dicati o n
X
Wee kl y C o ntact 
(e. g. via p h o ne, 
te xt, e mail)
X
S u bjects s h o ul d be 
c o ntacte d at least 
wee kl y a n d 
q uesti o ne d a b o ut 
t heir s yste mic 
c ortic oster oi d a n d 
a nti bi otics ( ot her 
t ha n t o pical nasal 
a nti bi otics) use a n d 
re m o ve d fr o m t he 
st u d y acc or di n g t o 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
t he re q uire me nts i n 
Secti o n 6. 2. 6 .
A d mi nister 1 
d ose of st u d y 
me dicati o n
X
S u bjects will use 
e Diar y t o a ns wer 
q uesti o ns a b o ut t heir 
C R S s y m pt o ms u p o n 
e x perie nci n g a facial 
pai n/ press ure/f ull ness 
of ≥ 6 o n N R S ( 0 -
1 0). T he s u bject will 
a d mi nister pre -
dis pe nse d st u d y dr u g 
if 1) t he facial 
pai n/ press ure/f ull ness 
re mai ns ≥ 6 o n N R S 
( 0-1 0); 2) t he s u bject 
has c o m plete d all 
re q uire d C R S 
assess me nt q uesti o ns 
i n t he e Diar y, a n d 3) 
t he s u bject h as n ot 
alre a dy t ake n 
pr o hi bite d 
me dic ati o ns (see 
pr ot oc ol S ecti o n 5. 4 ). 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 3 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
T he e Di ar y will 
pr o m pt t he s u bject 
t o t a ke st u d y 
me dic ati o n.
Ret ur n u n use d 
st u d y 
me dicati o n
X
e Diar y 
ret ur ne d/ 
re vie we d f or 
c o m plete ness
X
Staff t o re vie w a n d 
c o nfir m e Diar y 
e ntries wit h s u bjects, 
c o nfir m all data 
p oi nts are tra nsferre d 
t o t he s yste m, a n d 
reset e Diar y f or 
f ut ure s u bject use, 
P RI O R t o t he s u bject 
lea vi n g t he cli nic 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
Effic ac y Assess me nts
± wi n d o ws f or 
ti mefra me ar o u n d 
efficac y assess me nts 
( 1 5, 3 0, 4 5, 6 0, 9 0 
mi n, 2, 4, 8, a n d 2 4 
h o urs) will be 
a ut o mate d a n d 
ca pt ure d i n t he 
e Diar y.
Assess me nt of 
facial 
pai n/ press ure/ 
f ull ness
X
X
X
X
T his scale is ca pt ure d 
i n t he e Diar y
Assess me nt of 
nasal 
o bstr ucti o n 
(c o n gesti o n)
X
X
X
X
T his scale is ca pt ure d 
i n t he e Diar y.
Assess me nt of 
nasal disc har ge
X
X
X
X
T his scale is ca pt ure d 
i n t he e Diar y
Hea dac he Pai n
X
X
X
X
T his scale is ca pt ure d 
i n t he e Diar y f or 
s u bjects w h o re p ort 
c urre nt hea dac he 
pai n of m o derate or 
se vere at t he ti me of 
q ualif yi n g facial 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T a bl e 1
B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) S c h e d ul e of A s s e s s m e nt s
Pr oce d ure
Scree ni n g 
Visit 
( 3- 1 4 
d a ys)
B aseli ne Visit 
( R a n d o miz ati o n)
Wee kl y 
bet w ee n 
B aseli ne 
Visit 
a n d 
D osi n g
F aci al 
p ai n/ press ure/f ull ness 
≥6 o n N R S ( 0- 1 0)
D uri n g 
Tre at me nt 
1 5, 3 0, 4 5, 
6 0 a n d 9 0 
mi n utes 
P ost -D ose
D uri n g 
Tre at me nt 
2, 4, 8 
h o urs  
P ost -D ose
D uri n g 
Tre at me nt 
2 4 h o urs 
P ost -D ose
E n d of Tre at me nt 
Visit ( wit hi n 7 ( + 2) 
d a ys of tre ati n g f aci al 
p ai n/ press ure/f ull ness)
C o m me nts
pai n/ press ure/f ull ness
Patie nt Gl o bal 
I m pressi o n of 
C ha n ge      
( P GI-C)
X
T his scale is ca pt ure d 
i n t he e Diar y
Si n o -Nasal 
O utc o me Test 
( S N O T-2 2)
X
X
T his scale is ca pt ure d 
o n pa per at t he 
Baseli ne Visit a n d i n 
t he e Diar y at 2 4-
h o urs p ost -d ose. 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
4. 2. 1 
S cr e e ni n g P h a s e ( 3 t o 1 4 d a y s)
T he Scree ni n g P hase will be 3 t o 1 4 da y s ( + 2 da ys if nee de d f or sc he d uli n g p ur p oses). All 
s u bjects w h o si g ne d I nf or me d C o nse nt will be e ntere d i nt o t he I nteracti ve We b Res p o nse S yste m 
(IW R S)
a n d assi g ne d a s u bject i de ntifier. After o btai ni n g i nf or me d c o nse nt, s u bjects will 
u n der g o all scree ni n g pr oce d ures as detaile d i n Ta ble 1 . After all scree ni n g pr oce d ures are 
c o m plete, t he s u bject meets t he I ncl usi o n/ E xcl usi o n Criteria a n d la b test res ults ha ve bee n 
re vie we d by t h e I n vesti gat or, t he Baseli ne Visit will be sc he d ule d. 
S u bjects w h o were c o nsi dere d scree n fail ures ma y  be c o nsi dere d f or re-scree ni n g pr o vi de d t he 
i neli gi bilit y was d ue t o o ne of t he eli gi bilit y criteria t hat ma y ha ve c ha n ge d d ue t o me dical 
i nter ve nti o n or o ne of t he eli gi bilit y criteria m o difie d i n a pr ot oc ol a me n d me nt. A de q uate 
d oc u me ntati o n i n s o urce rec or ds m ust s u p p ort t he pre vi o usl y  faile d criteria. I n all p ossi ble re-
scree ni n g circ u msta nces, t he sit uati o n m ust be disc usse d wit h t he sp o ns or pri or t o re-scree ni n g, 
wit h a p pr o val i n writi n g fr o m t he sp o ns or pri or t o re -scree ni n g.  If a s u bject is a p pr o ve d f or re-
scree ni n g, a ne w s u bject n u m ber m ust be o btai ne d fr o m t he a p pr o priate st u d y-relate d sys te m. 
Re -scree ni n g will o nl y be per mitte d o ne ti me.
4. 2. 2
A c ut e Tr e at m e nt ( R a n d o mi z ati o n) P h a s e
It is esti mate d t hat a p pr o xi matel y 2 8 6 s u bjects will be ra n d o mize d t o res ult i n a p pr o xi matel y 2 0 0 
e val ua ble s u bjects . If t he s u bject meets all eli gi bilit y criteria, t he y will be ra n d o mize d at t he 
Baseli ne Visit via t he I W R S. S u bjects will be pr o vi de d wit h a n e Diar y. S t u d y pers o n nel will 
e d ucate t he s u bject o n t he pr o per use of t he e Diar y, acc urate re p orti n g a n d place b o res p o nse 
pri or t o t he s u bject lea vi n g t he office . 
After ra n d o mizati o n via t he I W R S, t he s u bject will be dis pe nse d a si n gle d ose of t he d o u ble -
bli n d st u d y  me dicati o n t o ta ke h o me. T he s u bject will be i nstr ucte d t o ta ke t heir st u d y 
me dicati o n wit hi n 4 5 da ys , as a n o ut patie nt, w he n (if) t he y ha ve facial pai n/ press ure/f ull ness 
w hic h reac hes a c urre nt i nte nsit y of ≥6 o n t he N R S ( 0 -1 0) a n d after t he y a ns wer e Diar y 
q uesti o ns a b o ut t heir c urre nt pai n a n d s y m pt o ms. T he s u bject will c o m plete q uesti o n naires i n
t heir e Diar y, at vari o us ti me p oi nts, f or 2 4 h o urs after ta ki n g st u d y me dicati o n t o rec or d efficac y 
a n d ot her q ualit y of life meas ures.
S u bjects i n t his st u d y  ma y be ra n d o mize d o nl y o nce. U n der n o circ u msta nces ma y a s u bject be 
re-ra n d o mize d.
4. 2. 2. 1
e Di ar y  D at a C oll e cti o n
S u bjects will rec or d t he date a n d ti me of d osi n g, pre-d ose a n d p ost -d ose efficac y assess me nts, 
a n d ot her q ualit y of life meas ures i n t heir e Diar y. S u bjects s h o ul d n ot d ose wit h st u d y  
me dicati o n u ntil t he facial pai n/ press ure/f ull ness reac hes a c urre nt i nte nsity of ≥6 o n t he N R S 
( 0-1 0) a n d t he y ha ve c o m plete d t he pre-d ose assess me nts i n t he e Diar y . Efficac y a n d q uality of 
life meas ure me nts i ncl u de t he f oll o wi n g: o nset ti me of facial pai n/ press ure/f ull ness at ti me of 
ta ki n g st u dy me dicati o n a n d after d osi n g at ti mes liste d i n Ta ble 1 . Nasal o bstr ucti o n 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
(c o n gesti o n) se verit y a n d Nasal disc har ge se verit y a n d will be rec or de d usi n g a N R S ( 0 -1 0) at 
t he o nset of t he facial pai n/ press ure/f ull ness ≥6 o n t he N R S ( 0 - 1 0) a n d after d osi n g at ti me s 
liste d i n Ta ble 1 . Hea dac he pai n se verit y will be rec or de d usi n g a 4-p oi nt Li kert scale (0 = N o ne; 
1 = Mil d; 2 = M o derate; 3 = Se vere) at t he o nset of t he facial pai n/ press ure/f ull ness ≥6 o n t he 
N R S ( 0 -1 0) a n d after d osi n g at ti mes liste d i n Ta ble 1 .
T he Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI -C) will be c o m plete d b y t he s u bject 2 4 h o urs 
after d osi n g. T he Si n o -Nasal O utc o me Test ( S N O T -2 2) q uesti o n naire will be c o m plete d o n 
pa per at t he Baseli ne Visit a n d o n t he e Diar y  at 2 4 h o urs after d osi n g.
After d osi n g wit h st u d y  me dicati o n, all ot her me dicati o n t o treat C R S s ym pt o ms is pr o hi bite d 
d uri n g t he 2 h o urs p ost -d ose. A t t he e n d of 2 h o urs after d osi n g wit h st u d y  me dicati o n (a n d after 
t he 2- h o ur assess me nts ha ve bee n c o m plete d o n t he e Diar y ) s u bjects will be per mitte d t o use t he 
f oll o wi n g resc ue me dicati o n: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y), or as piri n, i b u pr ofe n, 
na pr o xe n ( or a n y ot her t y pe of n o nster oi dal a nti -i nfla m mat or y dr u g [N S AI D ]), oral 
a nti hista mi nes ( n o n-se dati n g), oral dec o n gesta nts, t o pical nasal dec o n gesta nts, t o pical nasal 
a ntic h oli ner gics (all u p t o t he dail y rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g). T hese 
are t he o nl y me dicati o ns all o we d f or resc ue treat me nt after 2 h o urs p ost -d ose of st u d y  
me dicati o n. H o we ver, if nee de d, after 2 4 h o urs of a d mi nisteri n g t he o ne d ose of st u d y  
me dicati o n (a n d bef ore ret ur ni n g f or t he E n d of Treat me nt Visit) s u bject ma y  ta ke t heir 
prescri be d sta n dar d of care me dicati o ns f or treat me nt of C R S s y m pt o ms pr o vi de d all t he 
assess me nts ha ve bee n c o m plete d o n t he e Diar y . E xcl usi o nar y resc ue me dicati o n s uc h as, 
o pi oi ds a n d b utal bital c o m p o u n ds, are n ot all o we d o n t his st u d y. Si milarl y, if t he facial 
pai n/ press ure/f ull ness is relie ve d b y st u d y me dicati o n at 2 h o urs after d osi n g b ut t he n rec urs t o 
i nte nsit y le vel of ≥6 o n t he N R S ( 0 -1 0) bet wee n 2 a n d 2 4 h o urs, t he s u bject will be per mitte d t o 
ta ke t he sa me resc ue t hera p y as o utli ne d a b o ve.
S u bjects s h o ul d be e nc o ura ge d t o treat t he first q ualif y i n g facial pai n/ press ure/f ull ness (i nte nsit y 
le vel of ≥6 o n t he N R S ( 0 - 1 0)) t hat occ urs d uri n g t he treat me nt p hase. If s u bjects are u na ble t o 
treat t heir first q ualif yi n g facial pai n/ press ure/f ull ness d ue t o sc he d uli n g, etc., t he sa me 
me dicati o n restricti o ns w o ul d still a p pl y  (i.e., s u bjects w o ul d o nl y be per mitte d t o ta ke 
aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y ), or as piri n, i b u pr ofe n, na pr o xe n ( or a n y  ot her ty p e of 
n o nster oi dal a nti -i nfla m mat or y dr u g [N S AI D ]), oral a nti hista mi nes ( n o n-se dati n g), oral 
dec o n gesta nts, t o pical nasal dec o n gesta nts, t o pical nasal a ntic h oli ner gics [all u p t o t he dail y 
rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g]).
Si milarl y , f or treat me nt of n o n-q ualif y i n g facial pai n/ press ure/f ull ness (i.e., i nte nsit y le vel of < 6 
o n t he N R S ( 0- 1 0 )) that occ ur d uri n g t he ra n d o mizati o n peri o d bef ore a q ualif y i n g facial 
pai n/ press ure/f ull ness is re p orte d, s u bject will o nly be per mitte d t o use t he me dicati o ns liste d 
a b o ve. A ceta mi n o p he n ( o ver 1 0 0 0 m g / da y) is pr o hi bite d after ra n d o mizati o n e xce pt as resc ue
me dicati o n as descri be d i n Secti o n 5. 5 . In all circ u msta nces, t he s u bject will c o nti n ue t o 
c o m plete his or her e Diar y f or u p t o 2 4 h o urs after c o ns u mi n g t he st u d y me dicati o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
S u bjects s h o ul d ha ve access t o s y ste mic c ortic oster oi ds a n d a nti bi otics d uri n g t he trial f or 
treat me nt of sy m pt o ms if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he st u d y  if t he y 
recei ve t h ose t hera pies. 
4. 2. 3
E xt e n si o n P h a s e
N ot a p plica ble. 
4. 2. 4
W a s h o ut P h a s e
N ot a p plica ble. 
4. 2. 5
E n d of Tr e at m e nt
S u bjects will ret ur n t o t he st u d y  site wit hi n 7 da ys of st u d y treat me nt ( + 2 da ys) f or re vie w of t he 
e Diar y assess me nt, of me dicati o n c o m plia nce, a n d m o nit ori n g of t olera bilit y  a n d safety 
(i ncl u di n g vital si g ns, la b orat or y tests, a n d electr ocar di o gra p h y).  If a s u bject has N O T 
e x perie nce d a facial pai n/ press ure/f ull ness of s ufficie nt se verit y wit hi n 4 5 d a y s after 
ra n d o mizati o n, t he y still are re q uire d t o c o m plete all E O T visit pr oce d ures. All s u bjects m ust 
ret ur n u n use d st u dy me dicati o n or e m pt y pac ka gi n g a n d t he e Diar y t o t he st u d y ce nter.
4. 3
P o st St u d y  Ac c e s s t o T h er a p y
At t he e n d of t he st u d y t he sp o ns or will n o t c o nti n ue t o s u p pl y st u d y dr u g t o 
su bjects/ In vesti gat ors. T he I n vesti gat or s h o ul d e ns ure t hat t he s u bject recei ves t he a p pr o priate 
sta n dar d of care t o treat t he c o n diti o n u n der st u dy.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
5
P O P U L A TI O N
I n di vi d uals e ntere d i n t his trial will be s u bjects w h o s uffer fr o m c hr o nic r hi n osi n usitis wit h or 
wit h o ut nasal p ol y ps as s pecifie d u n der S ecti o n 5. 2 . T he treat me nt setti n g f or t hese s u bjects ma y 
i ncl u de cli nics, i nstit uti o ns, or pri vate office practices. S u bjects ma y  be recr uite d t hr o u g h a 
variet y of s o urces, i ncl u di n g referral fr o m p h ysicia ns a n d ot her healt h care pr ofessi o nals.
5. 1
N u m b er of S u bj e ct s
T he st u d y  will ra n d o mize a p pr o xi matel y 2 8 6 s u bjects t o res ult i n a p pr o xi matel y 2 0 0 e val ua ble 
s u bjects.. T he su bjects will be ra n d o mize d i n a 1: 1 rati o t o t he ri me ge pa nt or place b o treat me nt 
gr o u ps.
5. 2
I n cl u si o n Crit eri a
1.
Tar get p o p ulati o n
At t he Scree ni n g Visit, t he s u bject ha s a mi ni m u m 3- m o nt h hist or y of c hr o nic r hi n osi n usitis 
( C R S) wit h or wit h o ut p ol yps, dia g n os e d b y a healt hcare pr o vi der , i ncl u di n g all of t he 
f oll o wi n g:
a.
F aci al p ai n/ press ure/f ull ness A N D o ne or m ore of t he f oll o wi n g si g ns a n d s y m pt o ms: 
nasal disc har ge (a nteri or, p osteri or, or b ot h), nasal o bstr ucti o n (c o n gesti o n), or decrease d 
se nse of s mell.
b.
I nfl a m m ati o n is d oc u me nte d b y at least o ne of t hese t hree fi n di n gs:
i.
E n d osc o pic fi n di n g s of m uc o p ur ule nt drai na ge ( n ot clear) or e de ma i n t he mi d dle or 
s u peri or meat us , or a nteri or et h m oi d re gi o n
ii. P ol y ps i n nasal ca vit y or t he mi d dle or s u peri or meat us
iii R a di o gra p hic i ma gi n g s h o wi n g i nfla m mati o n of t he para nasal si n uses wit h partial 
o pacificati o n of at least t w o si n uses or c o m plete o pacificati o n of at least o ne si n us.
R es ults fr o m hist oric i ma gi n g, dia g n ostic or hist oric e n d osc o p y bef ore t he Scree ni n g 
Visit , b ut n ot ol der t ha n 1 2 m o nt hs , ca n be c o nsi dere d f or c o nfir mati o n of i nfla m mati o n.
c.
At least t w o e pis o des of facial pai n/ press ure/f ull ness of m o derate or se vere i nte nsit y o n a 
4- p oi nt rati n g scale ( 0 = N o ne, 1 = M il d, 2 = M o derate, 3 = S e vere) i n t he past 3 0 da ys 
pri or t o t he Scree ni n g Visit.
d.
S u bject wit h dail y  use of me dicati o ns liste d i n Secti o n 5. 5 is per mitte d t o re mai n o n 
t hera py if t he y ha ve bee n o n a sta ble d ose f or at least 1 m o nt h pri or t o t he Scree ni n g 
Visit , a n d t he d ose is n ot e x pecte d t o c ha n ge d uri n g t he c o urse of t he st u d y.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
e.
S u bje ct a grees t o n ot c o m me nce ne w t hera p y or a n y pai n ma na ge me nt tec h ni q ues t o treat 
t heir C R S d uri n g t he c o urse of t he st u d y.
2.
A ge a n d Re pr o d ucti ve Stat us
a.
Male a n d Fe male s u bjects ≥ 1 8 ye ars a n d ol der.
b.
S u bject meets re pr o d ucti ve criteria. Refer t o Secti o n 1 6. 3 f or re pr o d ucti ve criteria f or 
male (Secti o n 1 6. 3. 1 ) a n d fe male (Secti o n 1 6. 3. 2 ) s u bjects. 
c.
At t he Baseli ne Visit pri or t o dis pe nsi n g I n vesti gati o nal St u d y  Me dicati o n, W O C B P m ust 
ha ve a ne gati ve uri ne pre g na nc y  test.
3.
N o cli nicall y  si g nifica nt a b n or malit y i de ntifie d o n t he me dical or la b orat or y  e val uati o n. A 
s u bject wit h a cli nical a b n or malit y or la b orat or y para meters o utsi de t he refere nce ra n ge ma y 
be i ncl u de d o nl y if t he I n vesti gat or c o nsi ders t hat t he fi n di n g is n ot cli nicall y si g nifica nt a n d 
will n ot i ntr o d uce a d diti o na l ris k fact ors a n d will n ot i nterfere wit h t he st u d y pr oce d ures.
5. 3
E x cl u si o n Crit eri a
1.
Disease Tar get E xcl usi o n
a.
S u bject has a hist or y  of pri mar y hea dac he dis or der (e. g., mi grai ne, te nsi o n-t ype 
hea dac he, cl uster hea dac he), or M O H , dia g n ose d b y  a healt hcare pr o vi der , c o nsiste nt 
wit h dia g n ostic criteria acc or di n g t o t he I nter nati o nal Classificati o n of Hea dac he 
Dis or ders, 3 r d E diti o n (IC H D - 3). I nfre q ue nt te nsi o n-t ype hea dac he c o nsiste nt wit h 
dia g n ostic criteria acc or di n g t o t he I C H D-3 is n ot e xcl usi o nar y .
b.
S u bject has a hist or y  of nasal or facial s ur ger y wit hi n t he 6 m o nt hs pri or t o t he Scree ni n g 
Visit.
c.
S u bject has o n g oi n g r hi nitis me dica me nt osa (re b o u n d c o n gesti o n).
d.
S u bject has a hist or y  of nasal or u p per res pirat or y  i nfecti o n wit hi n t he 2 wee ks pri or t o 
t he Scree ni n g Visit.
e.
S u bject has a hist or y of i n vasi ve f u n gal r hi n osi n usitis.
f.
S u bject has dia g n ose d ac ute bacterial/ viral r hi n osi n usitis or has s y m pt o ms s u g gesti ve of 
a n ac ute e xacer bati o n of t heir c hr o nic r hi n osi n usitis (e. g., c o u g hi n g, fe ver, p ur ule nt 
disc har ge) wit hi n t he 2 wee ks pri or t o t he Scree ni n g Visit . If t he s u bject has dia g n ose d 
ac ute bacterial/ viral r hi n osi n usitis or has s y m pt o ms s u g gesti ve of a n ac ute e xacer bati o n 
of t heir c hr o nic r hi n osi n usitis bet wee n scree ni n g a n d d osi n g wit h st u d y dr u g, t he s u bject 
s h o ul d be disc o nti n ue d fr o m t he st u d y.
g.
S u bject has a dia g n osis of c y stic fi br osis.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
h.
S u bject has a dia g n osis of p ri mar y ciliar y d ys ki nesia (i m m otile-cilia s yn dr o me) .
i.
S u bject is c urre ntl y recei vi n g as piri n dese nsitizati o n or mai nte na nce t hera p y f or Sa mter’s 
Tria d.
j.
S u bject has a hist or y  of h yp o ga m ma gl o b uli ne mia.
k.
S u bject has a hist or y  of i m m u n o deficie nc y sy n dr o me .
l.
S u bject has a hist or y  of gra n ul o mat o us diseases.
m.
S u bject has a hist or y  of rec urre nt ac ute si n usitis (f o ur or m ore e pis o des per year of ac ute 
bacterial r hi n osi n usitis ( A B R S) wit h o ut si g ns or s y m pt o ms of r hi n osi n usitis bet wee n 
e pis o des).
n.
S u bject has a hist or y  of si n us m uc ocele wit hi n 1 year pri or t o t he Scree ni n g Visit.
o.
S u bject has a hist or y  of mali g na nt nasal or para nasal t u m or.
p.
S u bject has a hist or y  of o d o nt o ge nic si n usitis wit hi n 1 y ear pri or t o t he Scree ni n g Visit.
2.
Me dical Hist or y  a n d C o nc urre ntDiseases
a.
B o d y Mass I n de x 3 5. 0 k g/ m 2
b.
S u bject hist or y  wit h c urre nt e vi de nce of u nc o ntr olle d, u nstable or rece ntl y dia g n ose d 
car di o vasc ular disease, s uc h as isc he mic heart disease, c or o nar y  arter y vas os pas m, a n d 
cere bral isc he mia. S u bjects wit h M y ocar dial I nfarcti o n ( MI), Ac ute C or o nar y  Sy n dr o me 
( A C S), Perc uta ne o us C or o nar y Inter ve nti o n ( P CI), car diac s ur ger y , str o ke or tra nsie nt 
isc he mic attac k ( TI A) d uri n g t he 6 m o nt hs pri or t o t he Scree ni n g Visit .
c.
S u bject has u nc o ntr olle d h y perte nsi o n ( hi g h bl o o d press ure), or u nc o ntr olle d dia betes 
( h o we ver s u bjects ca n be i ncl u de d w h o ha ve sta ble h yperte nsi o n a n d/ or dia betes f or at 
least 3 m o nt hs pri or t o t he Scree ni n g Visit). A si n gle bl o o d press ure meas ure me nt of 
greater t ha n 1 5 0 m m H g s y st olic or 1 0 0 m m H g diast olic after 1 0 mi n utes of rest is 
e xcl usi o nar y.
d.
S u bject has a c urre nt dia g n osis of maj or de pressi o n, ot her pai n s y n dr o mes, ps yc hiatric 
c o n diti o ns (e. g., sc hiz o p hre nia), de me ntia, or si g nifica nt ne ur ol o gical dis or ders t hat, i n 
t he In vesti gat or’s o pi ni o n, mi g ht i nterfere wit h st u d y assess me nts.
e.
S u bject has a hist or y  of gastric, or s mall i ntesti nal s ur ger y (i ncl u di n g Gastric B ypass, 
Gastric Ba n di n g, Gastric Slee ve, Gastric Ball o o n, etc.), or has a disease t hat ca uses
mala bs or pti o n .
f.
S u bject has a hist or y  or c urre nt e vi de nce of a n y si g nifica nt a n d/ or u nsta ble me dical 
c o n diti o ns (e. g., hist or y of c o n ge nital heart disease or arr hyt h mia, k n o w n s us pecte d 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
i nfecti o n, he patitis B or C, or ca ncer) t hat, i n t he In vesti gat or’s o pi ni o n, w o ul d e x p ose 
t he m t o u n d ue ris k of a si g nifica nt a d verse e ve nt ( A E) or i nterfere wit h assess me nts of 
safety or efficac y d uri n g t he c o urse of t he trial. Se vere he patic i m pair me nt ( C hil d -P u g h 
C) is e xcl usi o nar y  i n all cases.
g.
S u bject has a h ist or y of, treat me nt f or, or e vi de nce of, alc o h ol or dr u g a b use or w h o ha ve 
met D S M -V criteria 2 4 f or a n y si g nifica nt s u bsta nce use dis or der wit hi n t he 1 2 m o nt hs 
pri or t o t he S cree ni n g V isit.
h.
S u bject s h o ul d be e xcl u de d if t he y  ha ve a p ositi ve dr u g scree n f or dr u gs of a b use t hat i n 
t he In vesti gat or’s j u d g me nt is me dicall y  si g nifica nt, i n t hat it w o ul d i m pact t he safety of 
t he s u bject or t he i nter pretati o n of t he st u d y res ults. In a d diti o n:
i.
Detecta ble le vels of c ocai ne, a m p heta mi ne, a n d p he nc y cli di ne ( P C P) i n t he dr u g 
scree n are e xcl usi o nar y. S u bjects w h o are p ositi ve f or a m p heta mi nes, a n d w h o are o n 
a prescri be d a m p heta mi ne me dicati o n f or a n a p pr o ve d i n dicati o n ( e. g., A D H D) will 
be all o we d i nt o t he st u d y at t he I n vesti gat or’s discreti o n.  T his deter mi nati o n b y t he 
I n vesti gat or must be well d oc u me nte d i n t he s u bject’s s o urce me dical rec or ds.  T he 
sti m ula nt d ose m ust be sta ble fr o m 3 m o nt hs pri or t o t he Scree ni n g Visit u ntil t he e n d 
of treat me nt visit occ urs.   
ii. Detecta ble le vels of ca n na bi n oi ds (e. g., marij ua na, C B D) i n t he dr u g scree n at t he 
Scree ni n g Visit are n ot e xcl usi o nar y, if i n t he In vesti gat or’s d oc u me nte d o pi ni o n t he 
s u bject d oes n ot meet D S M- V criteria 2 4 f or s u bsta nce use dis or der, a n d t he p ositi ve 
test d oes n ot si g nal a cli nical c o n diti o n t hat w o ul d i m pact t he safety of t he s u bject or 
i nter pretati o n of t he st u d y res ults.
3.
Aller gies a n d A d verse Dr u g Reacti o ns
a.
S u bject has a h ist or y of dr u g or ot her aller g y w hic h, i n t he o pi ni o n of t he In vesti gat or, 
ma kes t he s u bject u ns uita ble f or partici pati o n i n t he st u d y.
4.
Se x a n d Re pr o d ucti ve Stat us
a.
Fe males of c hil d - beari n g p ote ntial w h o are u n willi n g or u na ble t o use a n acce pta ble 
c o ntrace pti ve met h o d or a bsti ne nce t o a v oi d pre g na nc y  f or t he e ntire st u dy peri o d a n d f or 
2 8 da y s after d osi n g wit h st u d y  dr u g.
b.
W o me n w h o are pre g na nt , lactati n g or breastfee di n g.
c.
W o me n wit h a p ositi ve pre g na nc y  test o n e nr oll me nt or pri or t o st u d y dr u g
a d mi nistrati o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 4 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
5.
E C G a n d La b orat or y  TestFi n di n gs
a.
Esti mate d gl o mer ular filtrati o n rate (e G F R) acc or di n g t o t he re -e x presse d a b bre viate d 
(f o ur-varia bl e) M o dificati o n of Diet i n Re nal Disease ( M D R D) St u d y  e q uati o n < 3 0
ml/ mi n/ 1. 7 3 m 2
b.
E C G a b n or malities t hat , i n t he In vesti gat or’s o pi ni o n , ma kes t he s u bject u ns uita ble f or 
partici pati o n i n t he st u d y .
c.
T ota l ser u m bilir u bi n > 1. 5 x U L N ( O nl y a b n or mal val ues wit h cli nical j ustificati o n m ay 
be re pe ate d o nce f or c o nfir m ati o n d uri n g t he scree ni n g peri o d) . F or Gil bert’s 
s yn dr o me, direct bilir u bi n > 1 x U L N is e xcl usi o nar y .
d.
Ne utr o p hil c o u nt ≤ 1 0 0 0/ µ L  ( ore q ui vale nt).
e.
H b A 1c > 7 . 5 %
f.
A S T ( S G O T) or A L T ( S G P T) > 2 x U L N ( O nl y a b n or mal val ues wit h cli nical 
j ustificati o n m ay be re pe ate d o nce f or c o nfir m ati o n d uri n g t he scree ni n g peri o d ).
6.
E xcl u de d C urre nt or Rece nt Treat me nts
a.
S u bject has a hist or y  of a nti bi otics ( ot her t ha n t o pical nasal a nti bi otics) use wit hi n t he 1 4 
da ys  pri or t o Scree ni n g Visit.
b.
S u bject has a hist or y  of s yste mic c ortic oster oi ds use wit hi n t he 3 0 da y s pri or t o Scree ni n g 
Visit.
c.
S u bject has a hist or y  of c ortic oster oi d el uti n g si n us i m pla nts wit hi n t he 3 m o nt hs of date 
of i m pla nt (P R O P E L ®) or 6 m o nt hs of date of i m pla nt ( SIN U V A ® ) pri or t o Scree ni n g 
Visit.
d.
S u bject has a hist or y  of n o n -ster oi d i m m u n os u p pressa nts (i.e., calci ne uri n i n hi bit ors, 
i nterle u ki n i n hi bit ors, selecti ve i m m u n os u p pressa nts, T N F-i n hi bit ors, ot her 
i m m u n os u p pressa nts) use wit hi n t he 6 0 da y s pri or t o Scree ni n g Visit.
e.
S u bject has a hist or y of ne w or rece ntl y m o difie d aller ge n i m m u n ot hera p y wit hi n t he 3 
m o nt hs pri or t o Scree ni n g Visit.
f.
S u bject has a hist or y  of m o n ocl o nal a nti b o d y t hera p y (e. g., d u pil u ma b, me p oliz u ma b, 
o maliz u ma b, be nraliz u ma b , resliz u ma b) wit hi n t he 3 m o nt hs pri or t o Scree ni n g Visit.
g.
S u bject has a hist or y  of ne w or rece ntly m o difie d le u k otrie ne m o difiers t hera p y wit hi n 
t he 1 m o nt h pri or t o Scree ni n g Visit.
h.
S u bject has a hist or y of ne w or rece ntl y m o difie d β -a dre n oce pt or a g o nists t hera p y wit hi n 
t he 1 m o nt h pri or t o Scree ni n g Visit.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
i.
S u bject has ha d ast h ma e xacer bati o n re q uiri n g s ys te mic c ortic oster oi d treat me nt, 
e mer ge nc y de part me nt visit, or h os pitalizati o n w it hi n t he 3 m o nt hs pri or t o Scree ni n g 
Visit.
j.
U se of a ny pr o hi bite d c o nc o mita nt me dicati o n(s) as s pecifie d i n Secti o n 5. 4 .
7.
Ot her E xcl usi o n Criteria
a.
Pr is o ners or s u bjects w h o are i n v ol u ntar y i ncarcerate d.
b.
S u bjects w h o are c o m p uls oril y  detai ne d f or treat me nt of eit her a ps yc hiatric or p h ysical 
(e. g., i nfecti o us disease) ill ness.
c.
S u bject p artici pati o n i n cli nical trial wit h n o n -bi ol o gical i n vesti gati o nal a ge nts or 
i n vesti gati o nal i nter ve nti o nal treat me nts wit hi n t he 3 0 da ys pri or t o Scree ni n g Visit.
d.
S u bjects w h o ha ve pre vi o usl y  partici pate d i n a ny B H V -3 0 0 0/ B M S -9 2 7 7 1 1/ ri me ge pa nt 
st u d y.
e.
S u bject p artici pati o n i n cli nical trial wit h bi ol o gical i n vesti gati o nal a ge nts wit hi n t he 3 
m o nt hs pri or t o t he Scree ni n g Visit .
f.
S u bjects w h o meet criteria f or C -S S R S S uici dal I deati o n I te ms 4 or 5 wit hi n t he last 1 2 
m o nt hs pri or t o scree ni n g, O R s u bjects w h o e n d or se a ny of t he fi ve C -S S R S S uici dal 
Be ha vi or Ite ms (act ual atte m pt, i nterr u pte d atte m pt, a b orte d atte m pt, pre parat or y  acts, or 
be ha vi or) wit hi n t he last 1 0 y ears pri or t o scree ni n g, O R s u bjects w h o, i n t he o pi ni o n of 
t he In vesti gat or, prese nt a seri o us ris k of s uici de ( See Secti o n 6. 2. 5 ).
g.
Pla n ne d p artici pati o n i n a n y ot her i n vesti gati o nal cli nical trial w hile partici pati n g i n t his 
cli nical trial.
h.
S u bjects e n ga ge d i n, or wit h pla ns t o e n ga ge i n, liti gati o n or W or ker’s C o m pe nsati o n i n 
w hic h m o netar y  gai n or l oss ( or ot her c o m pe nsati o n) ma y affect t heir o bjecti ve 
partici pati o n i n t he trial.
i.
I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vi se d by t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers.
j.
S u bject u na ble t o c o m plete e Diar y i n de pe n de ntly i n t he o pi ni o n of t he I n vesti gat or.
Please see Secti o n 5. 4 f or Pr o hi bite d a n d Restricte d C o nc o mita nt Me dicati o ns a n d Secti o n 5. 5
f or Dail y a n d Resc ue Me dicati o ns .
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
5. 4
Pr o hi bit e d a n d R e stri ct e d C o n c o mit a nt M e di c ati o n s
T he bel o w me dicati o ns are pr o hi bite d pri or t o ra n d o mizati o n a n d d uri n g t he c o urse of t his st u d y  
or as s pecifie d. 
1.
Hist or y  of n o n-narc otic a nal gesic i nta ke o n ≥ 1 5 da y s per m o nt h f or greater ≥ 3 m o nt h ( e. g.,
aceta mi n o p he n, N S AI Ds, ga ba pe nti n etc.). ( Please refer t o Secti o n 5. 5 f or resc ue 
me dicati o n s). 
2.
Use of all aceta mi n o p he n or aceta mi n o p he n c o ntai ni n g pr o d ucts m ust be disc o nti n ue d at 
least 2 da ys pri or t o ra n d o mizati o n (aceta mi n o p he n ≤1 0 0 0 m g/ da y  is all o we d as resc ue 
me dicati o n, see Secti o n 5. 5 ). D uri n g t he scree ni n g p hase ( 3 t o 1 4 da y s) a n d t hr o u g h o ut t he 
st u d y, t he use of aceta mi n o p he n or aceta mi n o p he n c o ntai ni n g pr o d ucts at dail y  d osi n g le vels 
of greater t ha n 1 0 0 0 m g / da y is pr o hi bite d. 
3.
S y ste mic cortic oster oi ds (e. g., pre d nis o ne, pre d nis ol o ne, met h yl pre d nis ol o ne, 
beta met has o ne, de xa met has o ne, tria mci n ol o ne, h y dr oc ortis o ne, c ortis o ne) s h o ul d n ot be 
ta ke n 3 0 da y s pri or t o t he Scree ni n g Visit a n d t hr o u g h o ut t he st u d y. S u bjects s h o ul d ha ve 
access t o s yste mic c ortic oster oi ds d uri n g t he trial f or treat me nt of s ym pt o ms , if i n dicate d. 
H o we ver, s u bjects s h o ul d disc o nti n ue t he st u d y  if t he y recei ve t his t hera p y. 
4.
A nti bi otics, ot her t ha n t o pical nasal a nti bi otics, s h o ul d n ot b e ta ke n 1 4 da ys pri or t o t he 
Scree ni n g Visit a n d t hr o u g h o ut t he st u d y . S u bjects s h o ul d ha ve access t o a nti bi otics d uri n g 
t he trial f or treat me nt of s ym pt o ms , if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he 
st u d y if t he y recei ve t his t hera p y.
5.
M o n ocl o nal a nti b o d y  t hera p y (e. g., d u pil u ma b, me p oliz u ma b, o maliz u ma b, be nraliz u ma b, 
resliz u ma b) s h o ul d n ot be ta ke n 3 m o nt hs pri or t o t he Scree ni n g Visit a n d t hr o u g h o ut t he 
st u d y.
6.
St. J o h n’s W ort s h o ul d n ot be ta ke n 1 4 da y s pri or t o t he Baseli ne Visit a n d t hr o u g h o ut t he 
st u d y. 
7.
Bar bit urate -c o ntai ni n g pr o d ucts ( e. g., Fi oricet, Fi ori nal, b utal bital, p he n o bar bital) s h o ul d n ot 
be ta ke n 1 4 da y s pri or t o t he Baseli ne Visit a n d t hr o u g h o ut t he st u d y. 
8.
M o dafi nil ( P R O VI GI L ®) s h o ul d n ot be ta ke n 1 4 da y s pri or t o the Baseli ne Visit a n d 
t hr o u g h o ut t he st u dy.
9.
T he use of C G R P a nta g o nists ( bi ol o gic [e. g., Ai m o vi g® (ere n u ma b-a o oe), Aj o v y ®
(fre ma nez u ma b-vfr m), E m galit y ® ( galca nez u ma b-g nl m), V y e pti ® (e pti nez u ma b-jj mr)] or 
s mall m olec ule) ot her t ha n ri me ge pa nt is pr o hi bite d d uri n g t he st u d y. C G R P a nta g o nist 
bi ol o gics m ust be disc o nti n ue d 3 m o nt hs pri or t o t he Baseli ne Visit . C G R P s mall m olec ule 
a nta g o nists m ust be disc o nti n ue d 1 4 da y s pri or t o t he Baseli ne Visit a n d t hr o u g h o ut t he 
st u d y.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 0. Use of narc otic me dicati o n, s uc h as o pi oi ds ( e. g., m or p hi ne, c o dei ne, o x yc o d o ne a n d 
h y dr oc o d o ne) s h o ul d n ot be ta ke n 2 da y s pri or t o t he Baseli ne Visit a n d t hr o u g h o ut t he st u d y.
1 1. Use of ca n na bi n oi ds (e. g., marij ua na , C B D) is pr o hi bite d fr o m t he Baseli ne Visit a n d 
t hr o u g h o ut t he st u dy.
1 2. C o nc o mita nt use of str o n g C Y P 3 A 4 i n hi bit ors, s uc h as HI V Pr otease I n hi bit ors, He patitis C 
pr otease i n hi bit ors, certai n az ole a ntif u n gals, or clarit hr o m y ci n, is pr o hi bite d d uri n g t he 
st u d y. Str o n g C Y P 3 A 4 i n hi bit ors m ust be disc o nti n ue d 1 4 da y s pri or t o t he Baseli ne Visit 
a n d t hr o u g h o ut t he c o urse of t he st u d y. Please see Secti o n 1 6. 1 f or a d diti o nal res o urces.
1 3. C o nc o m ita nt use of m o derate t o str o n g C Y P 3 A 4 i n d ucers, s uc h as car ba maze pi ne, 
p he n y t oi n, or rifa m pi n, is pr o hi bite d d uri n g t he st u d y.  M o derate or str o n g C Y P 3 A 4 i n d ucers 
m ust be disc o nti n ue d 1 4 da y s pri or t o t he Baseli ne Vi sit a n d t hr o u g h o ut t he c o urse of t he 
stu d y . Please see Secti o n 1 6. 1 f or a d diti o nal res o urces.
1 4. A t ypical a nti ps y c h otics s uc h as A bilif y (ari pi praz ole), Z ypre xa ( ola nza pi ne), Ser o q uel 
( q uetia pi ne), Ge o d o n (zi prasi d o ne), or Ris per dal (ris peri d o ne) or De pa k ote/ De pa ke ne 
( val pr oic aci d/ val pr oate) s h o ul d n ot be ta ke n 9 0 da y s pri or t o t he Baseli ne Visit a n d 
t hr o u g h o ut t he st u dy.
1 5. L A M I CT A L (la m otri gi ne) s h o ul d n ot be ta ke n 9 0 da y s pri or t o t he Baseli ne Visit a n d 
t hr o u g h o ut t he st u dy.
1 6. T o pical nasal dec o n gesta nts s h o ul d n ot be ta ke n m ore t ha n 3 ti mes per wee k.
S u bjects wit h dail y  use of me dicati o ns liste d i n Secti o n 5. 5 are per mitte d t o re mai n o n t hera p y 
pr o vi de d t he y  ha ve bee n o n a sta ble d ose f or at least 1 m o nt h pri or t o t he Scree ni n g Visit .
L o w d ose as piri n ( e. g., u p t o 1 0 0 m g) f or d oc u me nte d car di o va sc ular pr o p h yla xis is all o we d.
5. 5
D ail y a n d R e s c u e M e di c ati o n s
Me dicati o n d oses m ust be st a ble f or at le ast o ne m o nt h pri or t o t he Scree ni n g Visit a n d 
t hr o u g h o ut t he st u dy. S u bjects ma y  use:

Sali ne a n d ot her n o n -me dicate d s pra y /ri nse (a d diti ves s uc h as deter ge nts, m oist urizers, 
m uc ol y tics are per mitte d) – mai ntai n d osi n g re gi me n esta blis he d pri or t o t he Scree ni n g Visit
A N D u p t o t w o of t he t o pic al n as al me dic ati o ns (st a ble d osi n g, n ot P R N, a n y i n dic ati o n):

T o pical nasal cortic oster oi ds (s pra y or ri nse)

T o pical nasal a nti bi otics a n d a ntif u n gal me dicati o ns (s pra y or ri nse)

T o pical nasal a nti hista mi nes ( n o n-se dati n g)
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L

T o pical nasal cr o m ol yn
A N D a n y of t he f oll o wi n g me dicati o ns (st a ble d osi n g, n ot P R N ):

Le u k otrie ne m o difiers 

Cr o m ol y n ( oral or i n halati o n)

Met h y l xa nti nes (e. g., t he o p h ylli ne, a mi n o p h ylli nes) 

M uc o acti ve a ge nts (e. g., g uaife nesi n, acet yl c ystei ne)
S u bjects wit h c o nc o mita nt ast h ma or C O P D ma y  re mai n o n t heir baseli ne S o C treat me nt if t he y 
ha ve bee n o n a sta ble d ose f or at least 1 m o nt h pri or t o t he Scree ni n g Visit a n d if n ot s pecificall y
liste d i n Secti o n 5. 4 Pr o hi bite d a n d Restricte d C o nc o mita nt Me dicati o ns , a n d t he d ose is n ot 
e x pecte d t o c ha n ge d uri n g t he c o urse of t he st u d y . S u bjects ma y  use t heir resc ue i n halers a n d/ or 
ne b ulizers as directe d b y t heir healt hcare pr o vi der ( H C P).
After d osi n g wit h st u d y me dic ati o n, all ot her C R S me dic ati o n is pr o hi bite d d uri n g t he 2 
h o urs p ost -d ose . A t t he e n d of 2 h o urs after d osi n g wit h st u d y  me dicati o n (a n d after t he 2- h o ur
assess me nts ha ve bee n c o m plete d o n t he e Diar y ), s u bjects will be per mitte d t o use t he f oll o wi n g 
resc ue me dicati o n: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y ), or as piri n, i b u pr ofe n, na pr o xe n ( or a n y 
ot her t y pe of n o n -ster oi dal a nti-i nfla m mat or y dr u g ( N S AI D)), oral a nti hista mi nes ( n o n-se dati n g), 
oral dec o n gesta nts, t o pical nasal dec o n gesta nts , t o pical nasal a ntic h oli ner gics (all u p t o t he daily 
rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g). T hese are t he o nly m e dicati o ns all o we d f or 
resc ue treat me nt after 2 h o urs p ost d ose of st u d y me dicati o n.  
H o we ver, if nee de d, after 2 4 h o urs of a d mi nisteri n g t he o ne d ose of st u d y me dicati o n (a n d 
bef ore c o mi n g i n f or t he E n d of Treat me nt Visit) s u bject ma y  ta ke t heir prescri be d sta n dar d of 
care me dicati o ns f or treat me nt of C R S s y m pt o ms pr o vi de d all t he assess me nts ha ve bee n 
c o m plete d o n t he e Diar y. E xcl usi o nar y  resc ue me dicati o n s uc h as o pi oi ds, b utal bital c o m p o u n ds, 
are n ot all o we d o n t his st u d y . Si milarl y , if t he facial pai n/ press ure/f ull ness is relie ve d b y st u d y 
me dicati o n at 2 h o urs after d osi n g b ut t he n rec urs t o i nte nsit y le vel of ≥6 o n N R S ( 0 -1 0) 
bet wee n 2 a n d 2 4 h o urs, t he s u bject will be per mitte d t o ta ke t he sa me resc ue t hera p y as o utli ne d 
a b o ve. I n all circ u msta nces, t he s u bject will al wa ys c o nti n ue t o c o m plete his or her e Diar y  
e ntries t hr o u g h t he 2 4-h o ur assess me nt after c o ns u mi n g t he st u d y  me dicati o n. 
Use of c o nc o mita nt me dicati o n after ra n d o mizati o n, i ncl u di n g resc ue me dicati o n, will be 
rec or de d by t he s u bject o n a pa per diar y a n d re p orte d t o t he site. T he site will rec or d all 
me dicati o ns t hat were ta ke n fr o m 1 4 da ys bef ore t he Scree ni n g Visit t hr o u g h t he e n d of t he E n d 
of Treat me nt Visit. 
D uri n g t he 4 5- d a y  Treat me nt P hase , if t he s u bject has a n o n -q u alif yi n g facial 
pai n/ press ure/f ull ness (i.e., facial pai n/ press ure/f ull ness < 6 o n a N R S ( 0- 1 0)), t he s u bject is 
per mitte d t o use o nl y  t he f oll o wi n g me dicati o ns: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y ), or as piri n, 
i b u pr ofe n, na pr o xe n ( or a n y ot her ty p e of n o nster oi dal a nti -i nfla m mat or y dr u g [N S AI D ]), oral 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
a nti hista mi nes ( n o n-se dati n g), oral dec o n gesta nts, t o pical nasal dec o n gesta nts, t o pical nasal 
a ntic h oli ner gics (all u p t o t he dail y rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g).
S u bjects s h o ul d ha ve access t o s y ste mic c ortic oster oi ds a n d a nti bi otics duri n g t he trial f or 
treat me nt of sy m pt o ms , if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he st u d y if t he y 
recei ve t h ose t hera pies. 
5. 6
C o ntr a c e pti o n
T he i n vesti gat or or t heir desi g nee, i n c o ns ultati o n wit h t he s u bject, will c o nfir m t hat t he s u bject
is utilizi n g a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual s u bject fr o m t he per mitte d 
list of c o ntrace pti o n met h o ds (see Secti o n 1 6. 3. 4 ) a n d will c o nfir m t hat t he s u bject has bee n 
i nstr ucte d i n its c o nsiste nt a n d c orrect use. 
T he i n vesti gat or or desi g nee will i nf or m t he s u bject of t he nee d t o use acce pta ble effecti ve
c o ntrace pti o n c o nsiste ntl y a n d c orrectl y a n d d oc u me nt t he c o n versati o n a n d t he s u bject’s 
affir mati o n i n t he s u bject’s c hart. S u bject s nee d t o affir m t heir c o nsiste nt a n d c orrect use of at 
least 1 of t he selecte d met h o ds of c o ntrace pti o n, c o nsi deri n g t hat t heir ris k f or pre g na nc y ma y 
ha ve c ha n ge d si nce t he last visit. 
I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he s u bject t o call i m me diately if t he 
selecte d c o ntrace pti o n met h o d is disc o nti n ue d a n d d oc u me nt t he re q uire me nt t o use a n alter nate 
pr ot oc ol -s pecifie d met h o d, i ncl udi n g if t he s u bject will n o l o n ger use a bsti ne nce as t he selecte d 
c o ntrace pti o n met h o d, or if pre g na nc y  is k n o w n or s us pecte d i n t he s u bject or part ner.
5. 7
Ot h er R e stri cti o n s a n d Pr e c a uti o n s
N ot a p plica ble. 
5. 8
Pr ot o c ol D e vi ati o n s a n d Q u alit y  T ol er a n c e Li mits
A n y  si g nifica nt e ve nt t hat d oes n ot c o m pl y wit h t he i ncl usi o n/e xcl usi o n criteria, st u dy c o n d uct, 
or st u d y  pr oce d ures will be d oc u me nte d as a de viati o n. De viati o ns will be d oc u me nte d a n d 
re p orte d t hr o u g h t he cli nical m o nit ori n g of t he trial. De viati o ns will be re p orte d t o t he I R B/ E C at 
t he fre q ue nc y re q uire d b y yo ur I R B/ E C. Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o 
recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot 
per mitte d . See Secti o n 1 0. 1 f or m ore i nf or mati o n o n pr ot oc ol de viati o ns.
I n a d diti o n, Q ualit y T olera nce Li mits ( Q T Ls) are pre defi ne d para meters t hat are m o nit ore d 
d uri n g t he st u d y. I m p orta nt de viati o ns fr o m t he Q T L s a n d a n y re me dial acti o ns ta ke n will be 
s u m marize d i n t he C S R.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6
S T U D Y C O N D U C T A N D D E S C RI P TI O N O F S T U D Y P R O C E D U R E S
6. 1
St u d y M at eri al s
T he f oll o wi n g st u d y materials m a y  be pr o vi de d:

I n vesti gat or File/ Re g ulat or y  Bi n der

P har mac y  Bi n der

I n vesti gati o nal Pr o d uct Ma n ual

Dr u g Acc o u nta bilit y  Lo gs

Sa m ple s o urce d oc u me nts, w here a p plica ble

Pa per diar y  t o rec or d C o nc o mita nt a n d Resc ue Me dicati o n (ta ke h o me f or s u bject) 

I n vesti gat or’s Br oc h ure

I nteracti ve We b-base d Res p o nse S y ste m (IW R S)
Ma n ual

Electr o nic Diar y  (e Diar y): 1 will be gi ve n t o eac h ra n d o mize d s u bject

I nstr ucti o ns f or t he e Diar y de vice a n d access t o t he p ortal

Si n o -Nasal O utc o me Test ( S N O T -2 2)

La b orat or y  Kits a n d La b orat or y Ma n ual

H o me Pre g na nc y  Test

E C G Mac hi ne a n d I nstr ucti o ns

C ol u m bia -S uici de Se verit y  Rati n g Scale 

Seri o us A d verse E ve nt ( S A E) f or ms (t o be use d o nl y if P S S A is n ot a vaila ble)

E x p os ure d uri n g Pre g na nc y  S u p ple me ntal F or ms

Pre g na nt Part ner Release of I nf or mati o n F or m
All sites will use a n Electr o nic Data Ca pt ure ( E D C) t o ol t o s u b mit st u d y  data t o t he sp o ns or ’s 
C R O. Electr o nic Patie nt Re p orte d O utc o mes (e P R O) will be use d f or all patie nt -rate d scales a n d 
will be ca pt ure d o n a n e Diar y . A ny assess me nt c o m plete d b y t he s u bject i n t he e Di ar y will be 
tra nsferre d fr o m t he site/s u bject t o t he ve n d or a n d fr o m t he ve n d or t o t he C R O a n d/ or sp o ns or. 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
N o a d diti o nal s o urce d oc u me nts are re q uire d f or scales a n d assess me nts c o m plete d b y  t he 
s u bject i n e Diar y.
Safet y  la b orat or y, plas ma, ser u m, i nstr ucti o ns f or all s peci me ns c ollecte d will be pr o vi de d b y a 
desi g nate d ce ntral la b orat or y . E C G e q ui p me nt, s u p plies, i nstr ucti o ns, a n d trai ni n g materials will 
be s u p plie d b y  a ce ntralize d E C G ve n d or.
6. 2 
S af et y  As s e s s m e nt s
6. 2. 1
Vit al Si g n s a n d P h y si c al M e a s ur e m e nt s ( H ei g ht a n d W ei g ht)
Sitti n g arterial s ys t olic a n d diast olic bl o o d press ure a n d p ulse rate, hei g ht, wei g ht a n d oral b o d y  
te m perat ure will be meas ure d at Scree ni n g a n d E n d of Treat me nt. Hei g ht a n d wei g ht will be 
meas ure d at Scree ni n g o nl y see Ta ble 1 .
6. 2. 2
El e ctr o c ar di o gr a m ( E C G)
A sta n dar d 1 2 -lea d E C G will be rec or de d d uri n g t he Scree ni n g P hase a n d at t he sc he d ule d visits 
as o utli ne d i n Ta ble 1 . E C G data will be s u b mitte d t o a ce ntral E C G ve n d or f or meas ure me nt 
a n d i nter pretati o n. T he fi nal E C G re p ort fr o m t he ce ntral ve n d or s h o ul d be mai ntai ne d i n t he 
s u bject’s s o urce d oc u me ntati o n a n d be use d f or t he fi nal i nter pretati o n of t he E C G rec or di n g. 
Base d o n t he ce ntral E C G ve n d or re p ort, t he I n vesti gat or will deter mi ne if s u bject is eli gi ble a n d 
if a n y a b n or malities are cli nicall y si g nifica nt or n ot. A n y cli nicall y si g nifica nt c ha n ges fr o m t he 
Scree ni n g E C G ma y  p ote ntiall y be AE s (Secti o n 1 6. 2 ) a n d s h o ul d be e val uate d f urt her, as 
cli nicall y warra nte d.
6. 2. 3
P h y si c al E x a m 
S u bjects will u n der g o a r o uti ne p h y sical e xa mi nati o n d uri n g t he Scree ni n g P hase a n d at t he 
sc he d ule d visits as o utli ne d i n Ta ble 1 . P h y sical e xa mi nati o ns i ncl u de e xa mi nati o n of t he heart, 
a b d o me n, l u n gs, a n d a n y ot her b o d y s ys te m t o be g ui de d by s y m pt o ms.
6. 2. 4
L a b or at or y  As s e s s m e nt s 
All pr ot oc ol -re q uire d la b orat or y assess me nts m ust be c o n d ucte d i n acc or da nce wit h t he 
la b orator y  ma n ual a n d t he Sc he d ule of Assess me nts (Ta ble 1 ). U nsc he d ule d cli nical la b orat or y  
meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess a n y percei ve d safet y 
iss ues.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F. T he 
la b orat or y re p orts m ust be file d wit h t he s o urce d oc u me nts. Cli nicall y si g nifica nt a b n or mal 
la b orat or y fi n di n gs are t h ose w hic h are n ot ass ociate d wit h t he u n derlyi n g disease, u nless j u d ge d 
b y  t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he s u bject’s c o n diti o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6. 2. 4. 1
S af et y  L a b or at or y T e sti n g
Bl o o d a n d uri ne sa m ples will be o btai ne d as o utli ne d i n Ta ble 1 f or cli nical la b orat or y 
e val uati o ns. A ce ntral la b orat or y ve n d or will be utilize d f or t his st u d y a n d a la b orat or y ma n ual 
will be pr o vi de d t o eac h site. If p ossi ble, s u bjects s h o ul d be f asti n g f or a mi ni m u m of 8 h o urs 
pri or t o all bl o o d dr a ws. H o we ver, if a s u bject is n ot fasti n g at a gi ve n visit, t he bl o o d dra w 
s h o ul d still be perf or me d, a n d t he n o n-fasti n g stat us s h o ul d be d oc u me nte d.
He m at ol o g y : He m o gl o bi n, he mat ocrit, re d bl o o d cell ( R B C) c o u nt, w hite bl o o d cell ( W B C)
c o u nt wit h differe ntial, a n d platelets.
Bl o o d c he mistr y/electr ol yte : S o di u m, p otassi u m, c hl ori de, bicar b o nate, calci u m; gl uc ose, B U N 
( urea), ser u m creati ni ne, uric aci d, A L T, A S T, al kali ne p h os p hatase, L D H, t otal pr otei n, 
al b u mi n, t otal bilir u bi n, direct bilir u bi n, i n direct bilir u bi n, C K. E n d of Treat me nt Visit –
ele vati o ns i n C K ( > 5 x U L N) ma y  ha ve f urt her C K fracti o nati o n tests perf or me d t hr o u g h t he 
ce ntral la b.  
Esti m ate d gl o mer ul ar filtr ati o n r ate : e G F R usi n g t he esti mate d M D R D f or m ula will be 
calc ulate d a n d re p orte d b y t he ce ntral la b at eac h visit t hat cli nical la b orat or y tests are c ollecte d 
as o utli ne d i n Ta ble 1 .
Uri n al ysis: p H, s pecific gra vit y , ket o nes, nitrites, ur o bili n o ge n, le u k oc yte esterase, pr otei n, 
gl uc ose a n d bl o o d. If bl o o d, pr otei n or le u k oc y tes are p ositi ve, refle x t o micr osc o pic 
e xa mi nati o n.
Uri ne Dr u g Scree n : F or dru gs of a b use.
F S H : F S H le vels will be meas ure d at t he Scree ni n g Visit o n p ost-me n o pa usal w o me n t o c o nfir m 
p ost -me n o pa usal stat us. F S H le vel testi n g is n ot re q uire d f or w o me n greater t ha n or e q ual t o 6 2 
ye ars ol d wit h a me n orr hea of greater t ha n or e q ual t o 1 y ear.
H b A 1c at scree ni n g.
Li pi d P a nel (tri gl yceri des, t otal c h olester ol, H D L, a n d L D L) will be meas ure d at t he Scree ni n g 
Visit.
Refle x tests: 
If A L T or A S T ≥ 3 x U L N O R t otal bilir u bi n ≥ 2 x U L N at a n y visit after t he baseli ne visit, t he 
ce ntral la b orat or y will perf or m refle x tests t hat ma y i ncl u de: C K, G G T, a n d a nti-viral ser ol o gies. 
S u bjects ma y  ha ve t o ret ur n t o t he st u d y site t o pr o vi de a d diti o nal bl o o d sa m ples f or t hese 
la b orat or y tests. 
A d diti o nal la b orat or y  tests ma y be o btai ne d t o e val uate la b orat or y  a b n or malities a n d/ or a d verse 
e ve nts. 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6. 2. 4. 2
Pr e g n a n c y  T e sti n g
Pre g na nc y  tests will be c o n d ucte d (ser u m, uri ne, or h o me pre g na nc y test), if a p pr o priate pri or t o 
ra n d o mizati o n, a n d as o utli ne d i n Ta ble 1 .
6. 2. 5
C ol u m bi a- S ui ci d e S e v erit y R ati n g S c al e ( C -S S R S) 
T he C ol u m bia -S uici de Se verit y Rati n g Scale ( C -S S R S) is a q uesti o n naire use d f or s uici de 
Assess me nt. 2 5 T he C -S S R S “ Scree ni n g versi o n” will be use d at t he Scree ni n g Visit a n d t he 
“ Si nce Last Visit versi o n” 2 6 will be use d at s u bse q ue nt visits i n t his st u d y.
T he C -S S R S Assess me nt is i nte n de d t o hel p esta blis h a pers o n’s i m me diate ris k of s uici de. T he 
C- S S R S is a cli nicia n a d mi nistere d scale t hat s h o ul d be a d mi nistere d b y a certifie d rater. T his 
scale will be c ollecte d o n site wit h a pa per f or m. T he C- S S R S s h o ul d be re vie we d b y t he 
I n vesti gat or or desi g nee bef ore t he s u bject is all o we d t o lea ve cli nic.
At t he Scree ni n g Visit, t he recall peri o d f or c o m pleti n g is 1 2 m o nt hs f or s uici dal i deati o n a n d 1 0 
ye ars f or s uici dal be ha vi or; at all ot her visits, t he recall peri o d f or c o m pleti n g t he C -S S R S is 
si nce t he last visit (Ta ble 1 ).
A n y  “ Yes” res p o nses m ust be i m me diatel y e val uate d b y t he i n vesti gat or. If t he In vesti gat or 
deter mi nes t hat a s u bject is at ris k of s uici de, self -har m, a p pr o priate meas ures t o e ns ure t he 
s u bject’s safety a n d o btai n me ntal healt h e val uati o n m ust be i m ple me nte d. I n s uc h 
circ u msta nces, t he s u bject m ust i m me diatel y  be disc o nti n ue d fr o m t he st u d y. T he e ve nt s h o ul d 
be rec or de d as eit her a n A E or S A E as deter mi ne d b y  t he I n vesti gat or a n d re p orte d wit hi n 2 4 
h o urs t o t he sp o ns or.  
6. 2. 6
W e e kl y  C o nt a ct
S u bject s s h o ul d be c o ntacte d (e. g., via p h o ne, te xt, e mail) at least wee kl y b y st u d y staff t o 
m o nit or (a n d re mi n d t he m t o re p ort) a n y s yste mic c ortic oster oi d a n d / or a nti bi otics ( ot her t ha n 
t o pical nasal a nti bi otics) use. If a s u bject re p orts ta ki n g o ne of t hese t hera pies bef ore d osi n g, 
st u d y staff s h o ul d wit h dra w t he s u bject fr o m t he st u d y, i nf or m t he s u bject t hat t he y s h o ul d n ot 
d ose wit h st u d y  me dicati o n, a n d sc he d ule an E n d of Treat me nt visit.
6. 3
Effi c a c y  As s e s s m e nt s
6. 3. 1
F a ci al p ai n/ pr e s s ur e/f ull n e s s
S u bjects will rec or d i n t heir e Diar y t heir c urre nt facial pai n/ press ure/f ull ness sc ore, o n a N R S ( 0 -
1 0) at t he ti me p oi nts i n dicate d i n Ta ble 1 .
6. 3. 2
N a s al o b str u cti o n ( c o n g e sti o n)
S u bjects will rec or d i n t heir e Diar y t heir c urre nt nasal o bstr ucti o n (c o n gesti o n) sc ore, o n a N R S 
( 0- 1 0) at t he ti me p oi nts i n dicate d i n Ta ble 1 .
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 5 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
6. 3. 3
N a s al di s c h ar g e
S u bjects will rec or d i n t heir e Diar y  t heir c urre nt nasal disc har ge (a nteri or, p osteri or, or b ot h)
sc ore, o n a N R S ( 0-1 0) at t he ti me p oi nts i n dicate d i n Ta ble 1 .
6. 3. 4
H e a d a c h e p ai n
S u bjects w h o re p ort m o derate or se vere hea dac he pai n at t he ti me of q ualif yi n g facial 
pai n/ press ure/f ull ness will rec or d i n t heir e Diar y  t heir c urre nt hea dac he pai n sc ore o n a 4 -p oi nt 
Li kert scale ( 0 = N o ne ; 1 = M il d; 2 = M o derate ; 3 = S e vere ) at t he ti me p oi nts i n dicate d i n Ta ble 
1.
6. 3. 5
R e s c u e M e di c ati o n
T he s u bject’s use of resc ue me dicati o n is rec or de d b y  t he s u bject o n a pa per diar y  a n d re vie we d 
b y  site staff.
6. 3. 6
P ati e nt Gl o b al I m pr e s si o n of C h a n g e ( P GI- C) Q u e sti o n n air e
T he P GI -C is a patie nt -rate d scale w hic h assesses h o w t he s u bject’s c urre nt ill ness state has 
c ha n ge d relati ve t o t he baseli ne visit. T he s u bject is as ke d t o rate a c ha n ge i n t heir o verall disease 
c o n diti o n o n a 7 -p oi nt L i kert scale, wit h t he f oll o wi n g res p o nse o pti o ns: 1 = ver y  m uc h 
i m pr o ve d, 2 = m uc h i m pr o ve d, 3 = mi ni mall y  i m pr o ve d, 4 = n o c ha n ge, 5 = mi ni mall y w orse, 6 
= m uc h w orse, a n d 7 = ver y  m uc h w orse. T he P GI -C is a gl o bal i n de x scale t hat ma y  be use d t o 
rate t he res p o nse of a c o n diti o n t o a t hera p y. T he e Diar y  is use d t o e val uate t he P GI - C
Q uesti o n naire at t he ti me p oi nts i n dicate d i n Ta ble 1 .
6. 3. 7
Si n o -N a s al O ut c o m e T e st ( S N O T -2 2)
S N O T -2 2 is a vali date d s ym pt o m - base d o utc o me meas ure t o assess t he b ur de n of C R S 
s ym pt o mat ol o g y . It is a 2 2 -ite m i nstr u me nt t hat i ncl u des b ot h nasal a n d e xtra-nasal s ym pt o ms 
s uc h as p o or slee p a n d m o o d dist ur ba nce. T he S N O T - 2 2 will be c ollecte d o n pa per at t he 
Baseli ne Visit a n d o n t he e Diar y at 2 4 h o urs p ost -d ose (see Ta ble 1 ).
6. 4
E arl y  Di s c o nti n u ati o n fr o m t h e St u d y
S u bjects M U S T disc o nti n ue i n vesti gati o nal pr o d uct (a n d n o n -i n vesti gati o nal pr o d uct at t he 
discreti o n of t he In vesti gat or) f or a n y  of t he f oll o wi n g reas o ns:

Wit h dra wal of i nf or me d c o nse nt (s u bject’s decisi o n t o wit h dra w f or a n y  reas o n).

A n y  cli nical a d verse e ve nt ( A E), la b orat or y a b n or malit y or i nterc urre nt ill ness w hic h, i n 
t he o pi ni o n of t he In vesti gat or or sp o ns or, i n dicates t hat c o nti n ue d partici pati o n i n t he 
st u d y is n ot i n t he best i nterest of t he s u bject.

Pre g na nc y
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L

Ter mi nati o n of t he st u d y b y  Pfizer I nc .

L oss of a bilit y  t o freely pr o vi de c o nse nt t hr o u g h i m pris o n me nt or i n v ol u ntar y 
i ncarcerati o n f or treat me nt of eit her a psyc hi atric or p h ysical (e. g., i nfecti o us disease) 
ill ness.

Use of s ys te mic c ortic oster oi ds.

Use of a nti bi otics ( ot her t ha n t o pical nasal a nti bi otics). 
All s u bjects w h o disc o nti n ue s h o ul d c o m pl y  wit h pr ot oc ol s pecifie d E n d of Treat me nt 
pr oce d ures as o utli ne d i n Ta ble 1 . T he o nly e xce pti o n t o t his re q uire me n t is w he n a s u bject 
wit h dra ws c o nse nt f or all st u d y  pr oce d ures or l oses t he a bilit y t o c o nse nt freely (i.e., is 
i nca pacitate d, i m pris o ne d, or i n v ol u ntaril y  i ncarcerate d f or t he treat me nt of eit her a psyc hiatric 
or p h y sical ill ness).
6. 5
L o st t o F oll o w U p
A s u bject will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peate dl y  fails t o ret ur n f or sc he d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.
T he f oll o wi n g acti o ns m ust be ta ke n a n d d oc u me nte d if a s u bject fails t o ret ur n t o t he cli nic f or a 
re q uire d st u dy visit:
T he site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit as s o o n as p ossi ble 
a n d c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule a n d 
ascertai n whet her or n ot t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y .
Bef ore a s u bject is dee me d l ost t o f oll o w u p, t he In vesti gat or or desi g nee m ust ma ke e ver y  eff ort 
t o re gai n c o ntact wit h t he s u bject ( w here p ossi ble, 3 tele p h o ne calls a n d, if necessar y, a certifie d 
letter t o t he s u bject’s last k n o w n maili n g a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact 
atte m pts s h o ul d be d oc u me nte d i n t he s u bject’s me dical rec or d.
S h o ul d t he s u bject c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve w it h dra w n fr o m 
t he st u d y.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
7
S T U D Y D R U G M A N A G E M E N T
7. 1
D e s cri pti o n of St u d y  Dr u g
7. 1. 1
I n v e sti g ati o n al Pr o d u ct
A n i n vesti gati o nal pr o d uct, als o k n o w n as i n vesti gati o nal me dici nal pr o d uct i n s o me re gi o ns, is 
defi ne d as f oll o ws:
A p har mace utical f or m of a n acti ve s u bsta nce or place b o bei n g teste d or use d as a refere nce i n a 
cli nical st u d y, i ncl u di n g pr o d ucts alrea d y wit h a mar keti n g a ut h orizati o n b ut use d or asse m ble d 
(f or m ulate d or pac ka ge d) i n a wa y differe nt fr o m t he a ut h orize d f or m, or use d f or a n 
u na ut h orize d i n dicati o n, or w he n use d t o gai n f urt her i nf or mati o n a b o ut t he a ut h orize d f or m.
T he i n vesti gati o nal pr o d uct s h o ul d be st ore d i n a sec ure area acc or di n g t o l ocal re g ulati o ns. It is 
t he res p o nsi bilit y of t he I n vesti gat or t o e ns ure t hat i n vesti gati o nal pr o d uct is o nl y dis pe nse d t o 
st u d y s u bjects. T he i n vesti gati o nal pr o d uct m ust be dis pe nse d o nly fr o m official st u d y sites b y 
a ut h orize d pers o n nel acc or di n g t o l ocal re g ulati o ns.
I n t his pr ot oc ol, i n vesti g ati o n al pr o d uct is/ are:
Ri me ge pa nt O D T a n d matc hi n g place b o.  T he ri me ge pa nt O D T a n d t he matc hi n g place b o a p pear 
i de ntical vis uall y, via t o uc h, s mell a n d taste.  
7. 1. 2
P a c k a gi n g, S hi p m e nt a n d St or a g e
T he pr o d uct st ora ge ma na ger s h o ul d e ns ure t hat t he st u d y  dr u g is st ore d i n acc or da nce wit h t he 
e n vir o n me ntal c o n diti o ns (te m perat ure a n d li g ht) as deter mi ne d b y t he sp o ns or. Please see t he 
I n vesti gati o nal Pr o d uct Ma n ual/I n vesti gat or ’s Br oc h ure f or s pecific c o n diti o ns. I f c o ncer ns 
re gar di n g t he q ualit y or a p peara nce of t he st u d y dr u g arise, d o n ot dis pe nse t he st ud y  dr u g a n d 
c o ntact t he sp o ns or/ C R O i m me diatel y .
7. 2
D o s e a n d A d mi ni str ati o n
O ne d ose of ri me ge pa nt O D T ( 7 5 m g) or matc hi n g place b o will be dis pe nse d t o t he s u bject a n d 
will be ta ke n at t he ti me t he s u bject has a facial pai n/ press ure/f ull ness t hat reac hes i ntensit y of ≥
6 o n t he N R S ( 0- 1 0) a n d after c o m pleti n g t he e Diar y q uesti o ns. 
7. 2. 1
M et h o d of A s si g ni n g S u bj e ct I d e ntifi c ati o n
At t he ti me of e nr oll me nt, i m me diatel y  after writte n i nf or me d c o nse nt is o btai ne d a n d bef ore 
perf or mi n g a n y st u d y -relate d pr oce d ures, eac h s u bject will be assi g ne d, t hr o u g h a n i nteracti ve 
we b res p o nse s y ste m (I W R S), a u ni q ue s u bject n u m ber f or i de ntificati o n t hr o u g h o ut t he st u d y.
T his s u bject n u m ber m ust n ot be re use d f or a n y ot her s u bject i n t he st u d y. T he 
p h y sicia n/c o or di nat or m ust c o ntact t he IW R S t o e nr oll eac h s u bject i nt o a ce ntralize d data base at 
t he ti me of si g ni n g c o nse nt.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
After c o m pleti o n of all scree ni n g e val uati o ns all eli gi ble s u bjects will be ra n d o mize d i n a 1: 1 
rati o t o t he ri me ge pa nt or matc hi n g place b o treat me nt gr o u ps. T he ra n d o mizati o n will be 
stratifie d b y t he prese nce of nasal p oly ps ( yes or n o). It is i m p orta nt t o c orrectl y e nter s u bjects 
w h o ha ve nasal p ol y ps i n t he I W R S s y ste m. O nce a s u bject is stratifie d i n t he IW R S, t his ca n n ot 
be c ha n ge d a n d will be c o nsi dere d a de viati o n.
Ra n d o mizati o n sc he d ules will be ge nerate d a n d ke pt b y  t he I WR S ve n d or i n a sec ure net w or k 
f ol der wit h access li mite d t o o nl y u n bli n de d tea m me m bers. Eac h s u bject w h o is q ualifie d f or 
treat me nt will be ra n d o mize d via t he IW R S ra n d o mizati o n o pt i o n. S u bjects will mai ntai n t heir 
s u bject n u m ber assi g ne d at scree ni n g t hr o u g h o ut t he trial. T he I W R S will pr o vi de t he d o u ble-
bli n d treat me nt assi g n me nts.
T he ra n d o mizati o n will tri g ger dis pe nsati o n f or t he s u bject a n d assi g n a b ottle n u m ber f or t he 
a p pr o priate ra n d o mize d treat me nt ty pe. T he dr u g is dis pe nse d at t he ti me of ra n d o mizati o n.
7. 2. 2
S el e cti o n a n d Ti mi n g of D o s e a n d A d mi ni str ati o n
St u d y  me dicati o n ( o ne 7 5 m g O D T or matc hi n g place b o) will be pac ka ge d i n a si n gle blister u nit 
i n a s u bject-s pecific b ottle. T here are n o d ose a dj ust me nts i n t his st u d y a n d s u bjects will recei ve 
o ne d ose t o treat o ne facial pai n/ press ure/f ull ness t hat reac hes i nte nsit y of ≥6 o n t he N R S ( 0- 1 0) 
wit hi n 4 5 da y s of ra n d o mizati o n ( Baseli ne Visit). S u bjects will be dis pe nse d t he st ud y  
me dicati o n at ra n d o mizati o n ( Baseli ne Visit) a n d will ta ke t he O D T fr o m t he blister/ b ottle at t he 
ti me of o nset of facial pai n/ press ure/f ull ness ≥6 o n t he N R S ( 0 -1 0) O N L Y after a ns weri n g 
q uesti o ns re gar di n g t heir C R S s ym pt o ms i n t he e Diar y  de vice. T he O D T s h o ul d be place d o n or 
u n der t he t o n g ue u ntil f ull y  diss ol ve d t he n s wall o we d.  S u bjects s h o ul d be i nstr ucte d t o use dr y 
ha n ds w he n ha n dli n g t he st u d y  me dicati o n.  
7. 2. 3  
D o s e M o difi c ati o n s
T here will be n o d ose a dj ust me nts i n t his st u d y .
7. 3
Bli n di n g a n d U n bli n di n g
Bli n di n g is critical t o t he i nte grit y of t his cli nical st u d y .  H o we ver, i n t he e ve nt of a me dical 
e mer ge nc y or pre g na nc y i n a n i n di vi d ual s u bject, i n w hic h k n o wle d ge of t he i n vesti gati o nal 
pr o d uct is critical t o t he s u bject’s ma na ge me nt, t he bl i n d f or t hat s u bject ma y be br o ke n b y t he 
treati n g p hys icia n. 
Bef ore brea ki n g t he bli n d of a n i n di vi d ual s u bject’s treat me nt, t he I n vesti gat or s h o ul d ha ve 
deter mi ne d t hat t he i nf or mati o n is necessar y , (i.e., t hat it will alter t he s u bject’s i m me diate 
ma na ge me nt). I n ma ny cases, partic ularl y w he n t he e mer ge nc y is clearl y n ot i n vesti gati o nal 
pr o d uct relate d, t he pr o ble m ma y  be pr o perly ma na ge d b y ass u mi n g t hat t he s u bject is recei vi n g 
acti ve pr o d uct wit h o ut t he nee d f or u n bli n di n g.  
I n cases of acci de ntal un bli n di n g, c o ntact t he Pfizer Me dical M o nit or a n d e ns ure e ver y  atte m pt 
t o preser ve t he bli n d is ma de.    
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
7. 4
Tr e at m e nt C o m pli a n c e
Res p o nsi ble st u d y  pers o n nel will dis pe nse t he st u d y dr u g.  Acc o u nta bilit y a n d c o m plia nce 
verificati o n s h o ul d be d oc u me nte d i n t he s u bject’s st u d y  rec or ds.  
S u bjects ha ve t o be c o u nsele d o n t he i m p orta nce of ta ki n g t he st u d y dr u g as directe d w he n a 
facial pai n/ press ure/f ull ness occ urs a n d reac hes i nte nsit y of ≥6 o n t he N R S ( 0 - 1 0).  If t he s u bject 
d oes n ot ha ve a facial pai n/ press ure/f ull ness ≥6 o n t he N R S ( 0 - 1 0) or ta ke t heir st u d y  
me dicati o n wit hi n 4 5 da ys of t he Baseli ne Visit, t he y  s h o ul d ret ur n t o t he cli nic f or t heir E n d of 
St u d y  Visit a n d ret ur n t heir st u d y me dicati o n.
7. 5
D e str u cti o n a n d R et ur n of St u d y Dr u g
All u n use d st u d y  dr u g ca n be se nt bac k t o t he dr u g de p ot f or destr ucti o n o nl y after bei n g 
i ns pecte d a n d rec o ncile d b y t he res p o nsi ble St u d y m o nit or or t he sp o ns or’s desi g nee. If it is site 
p olic y  t o destr oy st u d y dr u g o n site, it is t he I n vesti gat or’s res p o nsi bilit y t o e ns ure t hat 
arra n ge me nts ha ve bee n ma de f or t he dis p osal, pr oce d ures f or pr o per dis p osal ha ve bee n 
esta blis he d acc or di n g t o t he a p pl ica ble re g ulati o ns, g ui deli nes a n d i nstit uti o nal pr oce d ures, a n d 
a p pr o priate rec or ds of t he dis p osal ha ve bee n d oc u me nte d. T he u n use d st u d y  dr u gs ca n o nly be 
destr o y e d after bei n g i ns pecte d a n d rec o ncile d b y t he res p o nsi ble St u d y M o nit or or t he sp o ns or’s 
d esi g nee.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
8
A D V E R S E E V E N T S
A n A d verse E ve nt ( A E) is defi ne d as a n y ne w u nt o war d me dical occ urre nce or w orse ni n g of a 
pre -e xisti n g me dical c o n diti o n i n a s u bject or cli nical i n vesti gati o n s u bject a d mi nistere d a n 
i n vesti gati o nal ( me dici nal) pr o d uct a n d t hat d oes n ot necessarily ha ve a ca usal relati o ns hi p wit h 
t his treat me nt.  A n A E ca n t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g f or e xa m ple) s ym pt o m, or disease te m p orall y  ass ociate d wit h t he 
use of t he i n vesti gati o n al pr o d uct, w het her or n ot c o nsi dere d relate t o t he i n vesti gati o nal pr o d uct. 
A d verse e ve nts ca n be s p o nta ne o usl y  re p orte d or elicite d d uri n g a n o pe n-e n de d q uesti o ni n g, 
e xa mi nati o n, or e val uati o n of a s u bject. I n or der t o pre ve nt re p orti n g bias, s u bjects s h o ul d n ot be 
q uesti o ne d re gar di n g t he s pecific occ urre nce of o ne or m ore A Es.
If a s pecific dia g n osis or s yn dr o me is i de ntifie d b y t he I n vesti gat or, t his s h o ul d be rec or de d as 
t he A E, rat her t ha n rec or di n g (as se parate A Es) t he i n di vi d ual si g ns/s ym pt o ms or cli nicall y 
si g nifica nt la b orat or y a b n or malities k n o w n t o be ass ociate d wit h, a n d c o nsi dere d b y t he 
I n vesti gat or t o be a c o m p o ne nt of, t he disease/sy n dr o me.
Defi niti o n of ter ms rel ate d t o all A d verse E ve nts (seri o us a n d n o n -seri o us):
Mil d : Is us uall y transie nt a n d ma y  re q uire o nly mi ni mal treat me nt or t hera pe utic 
i nter ve nti o n. T he e ve nt d oes n ot ge nerall y  i nterfere wit h us ual acti vities of dail y li vi n g.
M o derate : Is us uall y alle viate d wit h a d diti o nal s pecific t hera pe utic i nter ve nti o n. T he e ve nt 
i nterferes wit h us ual acti vities of dail y  li vi n g, ca usi n g disc o mf ort b ut p oses n o si g nifica nt or 
per ma ne nt ris k of har m t o t he s u bject.
Se vere : I nterr u pts us ual acti vities of dail y li vi n g, si g nifica ntly affects cli nical stat us, or ma y 
re q uire i nte nsi ve t hera pe utic inter ve nti o n.
Life t hreate ni n g A Es t hat are c o nsi dere d life t hreate ni n g s h o ul d be c o nsi dere d S A Es.  A n A E is 
life t hreate ni n g if t he s u bject was at i m me diate ris k of deat h fr o m t he e ve nt as it occ urre d, i.e., it 
d oes n ot i ncl u de a reacti o n t hat if it ha d occ urre d i n a m ore seri o us f or m mi g ht ha ve ca use d 
deat h. F or e xa m ple, dr u g i n d uce d he patitis t hat res ol ve d wit h o ut e vi de nce of he patic fail ure 
w o ul d n ot be c o nsi dere d life t hreate ni n g e ve n t h o u g h dr u g i n d uce d he patitis ca n be fatal.
H os pitalizati o n : A Es re q uiri n g h os pitalizati o n s h o ul d be c o nsi dere d S A Es. H os pitalizati o n f or 
electi ve s ur ger y or r o uti ne cli nical pr oce d ures t hat are n ot t he res ult of A E (e. g., electi ve s ur ger y 
f or a pre-e xisti n g c o n diti o n t hat has n ot w orse ne d) nee d n ot be c o nsi dere d A Es or S A Es. If 
a n yt hi n g u nt o war d is re p orte d d uri n g t he pr oce d ure, t hat occ urre nce m ust be re p orte d as a n A E, 
eit her 'seri o us' or ' n o n -seri o us' acc or di n g t o t he us ual criteria.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Assess me nt f or Deter mi ni n g Rel ati o ns hi p of A E t o St u d y Dr u g :
T he relate d ness of eac h A E t o st u d y  dr u g m ust be classifie d base d o n me dical j u d ge me nt a n d 
acc or di n g t o t he f oll o wi n g cate g ories. T he defi niti o ns are as f oll o ws:
Relate d : T his cate g or y a p plies t o A Es t hat are c o nsi dere d, wit h a hi g h de gree of certai nt y , t o be 
relate d t o t he st u d y dr u g. A n A E ma y be c o nsi dere d relate d w he n it f oll o ws a te m p oral se q ue nce 
fr o m t he a d mi nistrati o n of st u d y dr u g, it ca n n ot reas o na bl y be e x plai ne d b y t he k n o w n 
c haracteristics of t he s u bject’s cli nical s tate, e n vir o n me nt, or t o xic fact ors, or ot her m o des of 
t hera py a d mi nistere d t o t he s u bject. A n A E ma y be c o nsi dere d relate d w he n it f oll o ws a k n o w n 
patter n of res p o nse t o t he st u d y  dr u g, or if t he A E rea p pears u p o n re-c halle n ge. T his cate g or y 
als o a p plies t o A Es t hat are c o nsi dere d t o ha ve a n u nli kel y c o n necti o n t o st u d y dr u g, b ut a 
relati o ns hi p ca n n ot be r ule d o ut wit h certai nty.
U nrelate d: T his cate g or y  a p plies t o A Es t hat are c o nsi dere d wit h a hi g h de gree of certai nt y t o be 
d ue o nl y  t o e xtra ne o us ca uses (e. g., s u bject’s cli nical state, e n vir o n me nt, t o xic fact ors, disease 
u n der st u d y , etc.) a n d d oes n ot meet t he criteria of ot her cate g ories a b o ve.
T here are t w o t y pes of a d verse e ve nts, Seri o us A d verse E ve nts ( S A E) a n d N o n -Seri o us A d verse 
E ve nts ( A Es).
8. 1
S eri o u s A d v er s e E v e nt s
8. 1. 1
D efi niti o n of S eri o u s A d v er s e E v e nt ( S A E )
A n S A E is a n y  e ve nt t hat meets a n y of t he f oll o wi n g criteria at a n y d ose:

Deat h

Life -t hreate ni n g

I n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n

Persiste nt or si g nifica nt disa bilit y /i nca pacity

C o n ge nital a n o mal y/ birt h defect i n t he offs pri n g of a s u bject w h o recei ve d ri me ge pa nt

Ot her: I m p orta nt me dical e ve nts t hat ma y  n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n, ma y  be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, 
t he y ma y je o par dize t he s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o mes liste d i n t his defi niti o n. E xa m ples of s uc h e ve nts are ( b ut n ot li mite d t o):
○
I nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m
○
Bl o o d d ys crasias or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
○
De vel o p me nt of dr u g de pe n de nc y  or dr u g a b use
○
P ote ntial dr u g i n d uce d li ver i nj ur y  (see Secti o n 8. 5 )
○
A b use or O ver d ose of me dicati o n
▪
P ote ntial st u d y  me dicati o n a b use (i ncl u di n g cases of e xcessi ve n o n-c o m plia nce wit h 
st u d y me dicati o n d osi n g i nstr ucti o ns or s u bjects w h o disc o nti n ue treat me nt wit h o ut 
ret ur ni n g st u d y me dicati o n) s h o ul d be d oc u me nte d i n t he s o urce rec or d a n d re p orte d 
as a n A E or S A E as a p pr o priate. I n vesti gat ors m ust m o nit or s u bjects f or p ossi ble 
cases of a b use of st u d y me di cati o n (s u bjects ta ki n g st u d y dr u g f or n o n -t hera pe utic 
p ur p oses, e. g., f or ps yc h oacti ve effects s uc h as hi g h or e u p h oria). I n vesti gat ors s h o ul d 
o btai n m ore i nf or mati o n a n d e x pla nati o n fr o m s u bjects w he n t here are st u d y  dr u g 
acc o u nta bilit y discre pa ncies
▪
P ot e ntial st u d y me dicati o n o ver d ose is defi ne d i n Secti o n 8. 3
I n ge neral, h os pitalizati o n si g nifies t hat t he s u bject has bee n detai ne d ( us uall y  i n v ol vi n g at least 
a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d 
n ot ha ve bee n a p pr o priate i n t he p h y sicia n's office or o ut patie nt setti n g. W he n i n d o u bt as t o 
w het her ' h os pitalizati o n' occ urre d or was necessar y, t he A E s h o ul d be c o nsi dere d seri o us.
T he f oll o wi n g h os pitalizati o ns are n ot c o nsi dere d S A Es i n Pfizer cli nical st u dies ( b ut ma y be 
c o nsi dere d n o n -seri o us A Es):

A visit t o t he e mer ge nc y  r o o m or ot her h os pital de part me nt < 2 4 h ours t hat d oes n ot res ult i n 
a n a d missi o n ( u nless c o nsi dere d “i m p orta nt me dical e ve nt” or e ve nt t hat is life t hreate ni n g) .

Electi ve s ur ger y  pla n ne d pri or t o si g ni n g c o nse nt.

A d missi o ns as per pr ot oc ol f or a pla n ne d me dical/s ur gical pr oce d ure.

R o uti ne healt h assess me nt re q uiri n g a d missi o n (i.e., r o uti ne c ol o n osc o p y ).

A d missi o n e nc o u ntere d f or a n ot her life circ u msta nce t hat carries n o beari n g o n healt h a n d 
re q uires n o me dical i nter ve nti o n (i.e., lac k of h o usi n g, care-gi ver res pite, fa mil y  
circ u msta nces).
Dis a b ilit y/i nc a p acit ati n g: A n A E is i nca pacitati n g or disa bli n g if t he e x perie nce res ults i n a 
s u bsta ntial a n d/ or per ma ne nt disr u pti o n of t he s u bject’s a bilit y t o carr y o ut n or mal life f u ncti o ns.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
8. 1. 2
C oll e cti o n a n d R e p orti n g S eri o u s A d v er s e E v e nt s
F oll o wi n g t he s u bject’s writte n c o nse nt t o partici pate i n t he st u d y, all S A Es, w het her relate d or 
n ot relate d t o st u d y  dr u g, m ust be c ollecte d, i ncl u di n g t h ose t h o u g ht t o be ass ociate d wit h 
pr ot oc ol -s pecific pr oce d ures. All S A Es m ust be c ollecte d t hat occ ur fr o m t he ti me t he s u bject
pr o vi des i nf or me d c o nse nt , t hr o u g h o ut t he c o urse of t he st u d y, a n d u p t o 3 0 da y s after last d ose. 
T he I n vesti gat or s h o ul d re p ort a ny S A E occ urri n g after t his ti me peri o d t hat is belie ve d t o be 
relate d t o st u dy dr u g or pr ot oc ol -s pecific pr oce dures.  
All S A Es s h o ul d be f oll o we d t o res ol uti o n or sta bilizati o n.
A n S A E re p ort s h o ul d be c o m plete d f or a n y e ve nt w here d o u bt e xists re gar di n g its stat us of 
seri o us ness.
If t he In vesti gat or belie ves t hat a n S A E is n ot relate d t o t he st u d y  dr u g, b ut is p ote ntiall y relate d 
t o t he c o n diti o ns of t he st u d y (s uc h as a wit h dra wal of pre vi o us t hera py or a c o m plicati o n relate d 
t o st u d y pr oce d ure), t he relati o ns hi p s h o ul d be s pecifie d i n t he narrati ve secti o n of t he S A E 
Re p ort. 
S A Es, w het her relate d or n ot relate d t o st u d y dr u g, o ver d ose w he n ass ociate d wit h a n S A E (see 
Secti o n 8. 3 ), p ote ntial dr u g i n d uce d li ver i nj ur y (see Secti o n 8. 5 ) a n d pre g na ncies (see 
Secti o n 8. 4 ) m ust be re p orte d wit hi n 2 4 h o urs of t he I n vesti gat or bec o mi n g a ware of t he e ve nt. 
T he I n vesti gat or is res p o nsi ble f or s u b mitti n g all a p plica ble e ve nts t o t he I n de pe n de nt Re vie w 
B oar d (I R B) as per t he I R B’s re p orti n g re q uire me nts . A d diti o nall y , t he I n vesti gat or, or 
desi g nate d staff, is res p o nsi ble f or e nteri n g t he S A E i nf or mati o n i nt o t he Case Re p ort F or m 
( C R F) a n d safety re p orti n g s yste m (i.e., e ve nt ter m, start/st o p dates, ca usalit y, a n d se verit y).
A n y  seri o us a d verse e ve nt m ust be re p orte d i m me diately or n o later t ha n 2 4 h o urs after 
a ware ness of t he e ve nt t o Pfizer D S U eit her via t he Pfizer S A E S u b missi o n Assista nt ( P S S A)
t o ol or as a writte n descri pti o n, usi n g t he Pfizer C T S A E re p ort f or m, t hat m ust be se nt b y  
facsi mile (fa x or e Fa x ) t o t he Pfizer D S U at 1- 8 6 6- 9 9 7- 8 3 2 2.
If o nl y li mite d i nf or mati o n is i nitiall y a vaila ble, f oll o w-u p re p orts are re q uire d. If a n o n g oi n g 
S A E c ha n ges i n its i nte nsit y or relati o ns hi p t o st u d y dr u g or if ne w i nf or mati o n bec o mes 
a vaila ble, a f oll o w- u p S A E re p ort s h o ul d be se nt wit hi n 2 4 h o urs of t he I n vesti gat or bec o mi n g 
a ware of t he u p date d i nf or mati o n usi n g t he sa me pr oce d ure use d f or t he tra ns missi o n of t he 
i nitial S A E a n d t he sa me e ve nt ter m s h o ul d be use d.
T he mi ni m u m i nf or mati o n re q uire d f or a n i nitial S A E re p ort is:

Se n der of re p ort ( Site n u m ber, I n vesti gat or na me)

S u bject i de ntificati o n ( s u bject n u m ber)

Pr ot oc ol n u m ber
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L

S A E ter m (if a n S A E is bei n g re p orte d)
8. 2
N o n -s eri o u s A d v er s e E v e nt s
A n o n -seri o us a dverse eve nt is a n A E n ot classifie d as seri o us. 
8. 2. 1
C oll e cti o n a n d R e p orti n g of N o n- S eri o u s A d v er s e E v e nt s
T he c ollecti o n of n o n -seri o us A E i nf or mati o n s h o ul d be gi n at t he ti me t he s u bject pr o vi des 
i nf or me d c o nse nt t hr o u g h t he E n d of Treat me nt Visit.  
N o n -seri o us a d verse e ve nts s h o ul d be f oll o we d u ntil c o ncl usi o n or sta bilizati o n, or re p orte d as 
S A Es if t he y  bec o me seri o us.  F oll o w -u p is als o re q uire d f or n o n -seri o us A Es t hat ca use 
i nterr u pti o n or disc o nti n uati o n of st u d y dr u g or t h ose t hat are prese nt at t he e n d of st u d y 
treat me nt. 
8. 2. 2
L a b or at or y  T e st A b n or m aliti e s
T he f oll o wi n g la b orat or y test a b n or malities s h o u l d be ca pt ure d o n t he n o n-seri o us A E C R F pa ge 
or S A E Re p ort F or m ( pa per or electr o nic) as a p pr o priate:

A n y  la b orat or y test res ult t hat is cli nicall y si g nifica nt or meets t he defi niti o n of a n S A E.

A n y  la b orat or y a b n or malit y t hat re q uire d t he s u bject t o ha ve t he st u d y dr u g disc o nti n ue d or 
i nterr u pte d.

A n y  la b orat or y a b n or malit y t hat re q uire d t he s u bject t o recei ve s pecific c orrecti ve t hera p y.
8. 3
O v er d o s e
A n o ver d ose is defi ne d as t he acci de ntal or i nte nti o nal a d mi nistrati o n of a n y d ose of a
pr o d uct t hat is c o nsi dere d b ot h e xcessi ve a n d me dic all y i m p ort a nt.
O ver d ose is re p orta ble t o Pfizer Safet y  o nly w he n ass ociate d wit h a n S A E. Details of a n y si g ns 
or s y m pt o ms a n d t heir ma na ge me nt s h o ul d be rec or de d i ncl u di n g details of a n y  treat me nts 
a d mi nistere d.
As y m pt o matic d osi n g err ors ( e. g., acci de ntall y ta ki n g t w o ta blets i nstea d of prescri be d d ose of 
o ne ta blet i n o ne cale n dar da y ) s h o ul d be re p orte d as de viati o ns.
8. 4
Pr e g n a n c y
If, f oll o wi n g t he B aseli ne V isit, it is s u bse q ue ntl y disc o vere d t hat a st u d y s u bject is pre g na nt or 
ma y  ha ve bee n pre g na nt at t he ti me of t he i n vesti gati o nal pr o d uct e x p os ure, i ncl u di n g d uri n g at 
least 6 half-li ves after t he pr o d uct a d mi nistrati o n, t he i n vesti gati o nal pr o d uct will be per ma ne ntly 
disc o nti n ue d i n a n a p pr o priate ma n n er (i.e., d ose ta peri n g if necessar y f or s u bject safety).  
Pr ot oc ol -re q uire d pr oce d ures f or st u dy disc o nti n uati o n a n d f oll o w -u p m ust be perf or me d o n t he 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 6 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
s u bject u nless c o ntrai n dicate d by t he pre g na nc y  (i.e., x-ra y st u dies). Ot her a p pr o priate pre g na nc y 
f ollo w- u p pr oce d ures s h o ul d be c o nsi dere d if i n dicate d.  
Sites s h o ul d i nstr uct patie nts t o c o ntact t he I n vesti gat or if t he y  bec o me pre g na nt d uri n g t he 
c o urse of t he st u d y. T he In vesti gat or m ust i m me diatel y  n otif y t he Pfizer Me dical M o nit or
( or 
desi g nee) a n d re p ort t he e ve nt b y  eit her usi n g t he P S S A t o ol or b y  c o m pleti n g a n E x p os ure
D uri n g Pre g na nc y ( E D P) S u p ple me ntal F or m f oll o wi n g t he S A E re p orti n g pr oce d ures as 
descri be d i n Secti o n 8. 1. 2 . 
F oll o w -u p i nf or mati o n re gar di n g t he c o urse of t he pre g na nc y , i ncl u di n g peri natal a n d ne o natal 
o utc o me a n d, w here a p plica ble offs pri n g i nf or mati o n m ust als o be re p orte d o n a n E D P 
S u p ple me ntal F or m.
A n y  pre g na nc y t hat occ urs i n a fe male part ner of a male st u d y s u bject s h o ul d be re p orte d t o t he 
Pfizer D S U . Inf or mati o n o n t his pre g na nc y  will be c ollecte d o n a n E D P S u p ple me ntal F or m, as 
a p pr o priat e. I n t he case of pater nal e x p os ure, t he i n vesti gat or will pr o vi de t he s u bject wit h t he 
Pre g na nt Part ner Release of I nf or mati o n F or m t o deli ver t o his part ner. T he i n vesti gat or m ust 
d oc u me nt i n t he s o urce d oc u me nts t hat t he s u bject was gi ve n t he Pre g na nt P art ner Release of 
I nf or mati o n F or m t o pr o vi de t o his part ner.
8. 5
P ot e nti al Dr u g I n d u c e d Li v er I nj ur y ( DI LI)
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y b ut a da pt are 
ter me d “a da pt ors.” I n s o me s u bjects, tra nsa mi nase ele vati o ns are a har bi n ger of a m ore seri o us 
p ote ntial o utc o me. T hese s u bjects fail t o a da pt a n d t heref ore are “s usce pti ble” t o pr o gressi ve a n d 
seri o us li ver i nj ur y, c o m m o nl y referre d t o as DI LI. S u bject s w h o e x perie nce a tra nsa mi nase 
ele vati o n a b o ve 3 × U L N s h o ul d be m o nit ore d m ore fre q ue ntl y t o deter mi ne if t he y  are 
“a da pt ors” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T a n d/ or A L T prece de T bili ele vati o ns ( > 2 × 
U L N) b y se veral da ys or wee ks. T he i ncrease i n T bili t y picall y  occ urs w hile A S T/ A L T is/are 
still ele vate d a b o ve 3 × U L N (ie, A S T/ A L T a n d T bili val ues will be ele vate d wit hi n t he sa me 
la b orat or y sa m ple). I n rare i nsta nces, b y t he ti me T bili ele vati o ns are detecte d, A S T/ A L T val ues 
mi g ht ha ve decrease d. T his occ urre nce is still re gar de d as a p ote ntial DI LI. T heref ore, a b n or mal 
ele vati o ns i n eit her A S T  O R A L T i n a d diti o n t o T bili t hat meet t he criteria o utli ne d bel o w are 
c o nsi dere d p ote ntial DI LI (assesse d per H y ’s la w criteria) cases a n d s h o ul d al wa ys be c o nsi dere d 
i m p orta nt me dical e ve nts, e ve n bef ore all ot her p ossi ble ca uses of li ver i nj ur y ha ve bee n 
e xcl u de d.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he s u bject’s 
i n di vi d ual baseli ne val ues a n d u n derlyi n g c o n diti o ns. S u bject s w h o prese nt wit h t he f oll o wi n g 
la b orat or y a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI ( H y’s la w) cases t o 
defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

S u bject s wit h A S T/ A LT a n d T bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A LT val ues ≥3 × U L N A N D a T bili val ue ≥2 × U L N 
wit h n o e vi de nce of he m ol y sis a n d a n al kali ne p h os p hatase val ue < 2 × U L N or n ot a vaila ble.

F or s u bjects wit h baseli ne A S T O R A L T O R T bili val ues a b o ve t he U L N, t he f oll o wi n g 
t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, de pe n di n g o n w hic h 
val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T val ues 
≥2 ti mes t he baseli ne val ues A N D ≥3 × U L N; or ≥8 × U L N ( w hic he ver is s maller).

Pree xisti n g val ues of T bili a b o ve t he n or mal ra n ge: T bili le vel i ncrease d fr o m baseli ne 
val ue b y a n a m o u nt of ≥1 × U L N or if t he val ue reac hes ≥3 × U L N ( w hic he ver is 
s maller).
Rises i n A S T/ A L T a n d T bili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d
in di vi d uall y  base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or. T he s u bject s h o ul d 
ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, prefera bl y wit hi n 4 8 h o urs 
fr o m a ware ness of t he a b n or mal res ults. T his e val uati o n s h o ul d i ncl u de la b orat or y tests, detaile d 
hist or y, a n d p h ysical assess me nt.
If a ny p ote ntial DI LI is i de ntifie d a n d meets t he criteria a b o ve, t he Pfizer Me dical M o nit or ( or 
desi g nee) s h o ul d i m me diatel y  be c o ntacte d f or f urt her i nstr ucti o n o n w het her t he s u bject m ust 
disc o nti n ue fr o m t he trial a n d a p pr o priate f oll o w- u p re q uire me nts . 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A L T a n d T bili 
ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y ’s la w) cases if n o ot her reas o n 
f or t he L F T a b n or malities has yet bee n f o u n d. S uc h p ote nti a l DI LI ( H y’s l a w) c ases are t o be 
re p orte d as S A Es, irres pecti ve of a v ail a bilit y of all t he res ults of t he i n vesti g ati o ns 
perf or me d t o deter mi ne eti ol o g y of t he L F T a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all re s ults of reas o na ble 
i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
8. 6
A d v er s e E v e nt s of S p e ci al I nt er e st
N o ne
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
8. 7
E n vir o n m e nt al E x p o s ur e, E x p o s ur e D uri n g Br e a stf e e di n g, a n d 
O c c u p ati o n al E x p o s ur e
E n vir o n me ntal e x p os ure occ urs w he n a pers o n n ot e nr olle d i n t he st u d y as a s u bject recei ves 
u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y  i nter ve nti o n. S uc h e x p os ure ma y or ma y 
n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal e x p os ure i ncl u de 
healt hcare pr o vi ders, fa mil y  me m bers, a n d ot hers w h o ma y be e x p ose d. A n e n vir o n me ntal 
e x p os ure ma y i ncl u de E D P, e x p os ure d uri n g breastfee di n g ( E D B ), a n d occ u pati o nal e x p os ure.
A n y  s uc h e x p os ures t o t he st u d y i nter ve nti o n u n der st u dy are re p orta ble t o Pfizer Safet y wit hi n 
2 4 h o urs of i n vesti gat or a ware ness.
8. 7. 1
E x p o s ur e D uri n g Br e a stf e e di n g
A n E D B occ urs if:

A fe male s u bject is f o u n d t o be breastfee di n g w hile recei vi n g or after disc o nti n ui n g st u d y 
i nter ve nti o n.

A fe male n o n s u bject is f o un d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n 
e x p ose d t o st u d y i nter ve nti o n (i.e., e n vir o n me ntal e x p os ure). A n e xa m ple of e n vir o n me ntal 
E D B is a fe male fa mil y  me m ber or healt hcare pr o vi der w h o re p orts t hat s he is breastfee di n g 
after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y  i n gesti o n.   
T he i n vesti gat or m ust re p ort E D B t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nf or mati o n m ust be re p orte d via 
P S S A t o ol or b y  c o m pleti n g t he C T S A E Re p ort F or m . W he n E D B occ urs i n t he setti n g of 
e n vir o n me ntal e x p os ure, t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he s u bject e nr olle d i n t he 
st u d y, s o t he i nf or mati o n is n ot rec or de d o n a C R F. H o we ver, a c o p y of t he c o m plete d re p ort is 
mai ntai ne d i n t he i n vesti gat or site file.
A n E D B re p ort is n ot create d w he n a Pfizer dr u g s pecificall y a p pr o ve d f or use i n breastfee di n g 
w o me n (e . g., vita mi ns) is a d mi nistere d i n acc or da nce wit h a ut h orize d use. H o we ver, if t he i nfa nt 
e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d t o get her wit h t he E D B.
8. 7. 2
O c c u p ati o n al E x p o s ur e
T he i n vesti gat or m ust re p ort a n y  i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety wit hi n 2 4 
h o urs of t he i n vesti gat or ’s a ware ness via P S S A t o ol or b y  c o m pleti n g t he C T S A E Re p ort F or m
re gar dless of w het her t here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal 
e x p os ure d oes n ot pertai n t o a s u bject e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a 
C R F; h o we ver , a c o p y of t he c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
8. 8
L a c k of E ffi c a c y
T he i n vesti gat or m ust re p ort si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of 
efficac y.  Lac k of efficac y or fail ure of e x pecte d p har mac ol o gical acti o n is re p orta ble t o Pfizer 
Safet y  o nl y if ass oci ate d wit h a n S A E .
8. 9
M e di c ati o n E rr or s
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y i nter ve nti o n 
b y  t he wr o n g s u bject, or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
Me dicati o n err ors are rec or de d a n d re p orte d as f oll o ws:
Rec or de d o n t he Me dic ati o n 
Err or P a ge 
of t he C R F
Rec or de d o n t he 
A d verse E ve nt P a ge 
of t he C R F
Re p orte d o n C T S A E 
Re p ort F or m / vi a P S S A t o 
Pfizer S afet y Wit hi n 2 4 
H o urs of A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y  A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y  if ass ociate d wit h a n 
S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g s u bject e x p os ure t o t he st u d y i nter ve nti o n

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o or d o 
n ot i n v ol ve t he st u d y  s u bject.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y  t he i n vesti gat or, 
s uc h me dicati o n err ors occ urri n g t o a st u dy s u bject are rec or de d o n t he me dicati o n err or pa ge of 
t he C R F, w hic h is a s pecific versi o n of t he A E pa ge a n d, if a p plica ble, a n y  ass ociate d seri o us a n d 
n o nseri o us A E(s) are rec or de d o n t he A E pa ge of t he C R F .
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs. 
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4 h o urs via P S S A t o ol or b y  
c o m pleti n g t he C T S A E Re p ort F or m o nl y w he n ass oci ate d wit h a n S A E.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
9
S T A TI S TI C S
C o m plete details o n t he statistical met h o ds f or t his st u d y  ma y be f o u n d t he Statistical A nal ysis 
Pla n ( S A P).
9. 1
G e n er al Pr o c e d ur e s
Cate g orical varia bles are ta b ulate d wit h c o u nts a n d perce nta ges. C o nti n u o us varia bles are 
s u m marize d wit h u ni variate statistics (e. g., n, mea n, sta n dar d err or, me dia n, mi ni m u m a n d 
ma xi m u m).
F or t he calc ulati o n of descri pti ve statistics of o bser ve d data, s u bjects m ust ha ve a baseli ne val ue 
t o be e val ua ble f or e n d p oi nts base d o n val ues a n d c ha n ges fr o m baseli ne o ver ti me.
Ta b ulati o n s of t he f oll o wi n g e n d p oi nts prese nt t he n u m ber of u ni q ue s u bjects wit h a n e ve nt: 
pr ot oc ol de viati o ns; i nterr u pti o ns of st u d y  t hera p y; n o nst u d y me dicati o ns; a d verse e ve nts; a n d 
la b orat or y a b n or malities. T h us, f or t hese e n d p oi nts, m ulti ple occ urre nces of t he sa me e ve nt are 
c o u nte d o nl y o nce per s u bject.
9. 2
S a m pl e Si z e
If 7 0 % of t he 2 8 6 ra n d o mize d (1 4 3 per treat me nt ar m) ha ve a facial pai n/ press ure/f ull ness w hic h 
reac hes pai n i nte nsit y of ≥6 o n t he N R S ( 0- 1 0) i n t he all otte d ti me peri o d, a n d c o m plete t heir 
e Diar y i n t he 2 4 h o urs f oll o wi n g, we e x pect r o u g hl y 2 0 0 t otal or 1 0 0 per treat me nt gr o u p i n t he 
m o difie d i nte nt t o treat ( mI T T) p o p ulati o n f or a nal y sis. 
Ass u mi n g ri me ge pa nt pr o vi des a 2 -p oi nt re d ucti o n i n N R S pai n, a n d a 1. 3 5- p oi nt a d va nta ge o ver 
place b o o n t he pri mar y  e n d p oi nt, a n d a c o m m o n sta n dar d de viati o n of 3. 0, t he n t he st u d y will 
ha ve r o u g hl y 8 8 % p o wer o n t he pri mar y e n d p oi nt. T he esti mates f or c ha n ge fr o m baseli ne i n 
N R S a n d c o m m o n sta n dar d de viati o n are c o nsiste nt wit h a m o dest re d ucti o n i n pai n o ver place b o 
a n d a c o nser vati ve sta n dar d de viati o n esti mate, as t hese varie d wi del y i n pre vi o us st u dies
e xa mi ni n g C R S .2 7
9. 3
P o p ul ati o n s f or A n al y si s a n d E sti m a n d s
T he set of e nr olle d s u bjects c o nsists of all s u bjects w h o si g ne d t he i nf or me d c o nse nt f or m a n d 
were assi g ne d a s u bject i de ntificati o n n u m ber.
T he set of ra n d o mize d s u bjects c o nsists of e nr olle d s u bjects w h o were assi g ne d a ra n d o mize d 
treat me nt gr o u p .
T he set of treate d s u bjects c o nsists of e nr olle d s u bjects w h o ta ke st u d y t hera p y ( ri me ge pa nt or 
place b o) . 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T he M o difie d I nte nt t o Treat ( mI T T) set c o nsists of ra n d o mize d s u bjects t hat ta ke st u d y  t hera p y, 
ha ve a facial pai n/ press ure/f ull ness w hic h reac hes pai n i nte nsit y of ≥6 o n t he N R S ( 0 - 1 0) pri or 
t o a d mi nistrati o n of treat me nt, a n d pr o vi de at least o ne p ost -baseli ne efficac y  data p oi nt.  
Esti m a n d s
T he esti ma n d is a s ys te matic descri pti o n of t he treat me nt effect t o be q ua ntifie d i n or der t o
a ns wer t he trial's researc h o bjecti ve. T he esti ma n d c o nsists of t he f oll o wi n g 5 attri b utes: 
Treat me nt, P o p ulati o n, Varia ble, P o p ulati o n- Le vel S u m mar y , a n d Ha n dli n g of I nterc urre nt 
E ve nts (I C Es). Esti ma n d f or pri mar y  o bjecti ve is disc usse d bel o w.
Pri mar y  Esti ma n d:

Treat me nt: Ri me ge pa nt f or m ulate d i n a 7 5 m g O D T (place d o n or u n der t he t o n g ue) or a 
matc hi n g place b o

P o p ulati o n : S u bject s as defi ne d by i ncl usi o n/ e xcl usi o n criteria of t he st u d y.  

Varia ble: C ha n ge fr o m baseli ne of facial pai n/ press ure/f ull ness o n N R S ( 0 -1 0) sc ore at 2 
h o urs p ost -d ose.

P o p ulati o n -Le v el S u m mar y: Differe nce i n mea ns a n d 9 5 % CI, i n c ha n ge fr o m baseli ne of 
facial pai n/ press ure/f ull ness o n N R S ( 0-1 0) sc ore at 2 h o urs p ost -d ose, bet wee n 
Ri me ge pa nt a n d place b o.

I nterc urre nt E ve nt:
o
Use of n o nst u d y resc ue me dicati o ns o n or bef ore 2 h o urs p ost -d ose         
H y p ot hetical strate g y : I n t he e ve nt a s u bject uses a n o nst u d y resc ue me dicati o n o n 
or bef ore 2 h o urs p ost -d ose, all data p oi nts after resc ue me dicati o n was 
a d mi nistere d are set t o missi n g.  It is ass u me d t hat, if t he i nterc urre nt e ve nt ha d 
n ot occ urre d a n d s u bject ha d f oll o we d t he patter n of ot her s u bjects w h o c o nti n ue d 
f oll o w-u p wit h o ut n o nst u d y  resc ue me dicati o n, t heir efficac y w o ul d ha ve bee n 
li ke t he efficac y of s u bjects fr o m t he sa me treat me nt gr o u p w h o di d n ot use resc ue 
me dicati o n.  T his is li ke missi n g at ra n d o m ( M A R) strate g y .
o
All ot her i nterc urre nt e ve nts
   
Treat me nt p olic y  strate g y: All a vaila ble assess me nts o n t he s u bject are use d 
re gar dless of ot her i nterc urre nt e ve nts.
                        
Si milarl y , esti ma n ds f or ot her o bjecti ves will be disc usse d i n detail i n t he statistical a nal ysis 
pla n.
9. 4
St ati sti c al M et h o d s
9. 4. 1
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s
Ta b ulati o ns of de m o gra p hic a n d baseli ne c haract eristics are ma de f or: s u bjects ra n d o mize d b ut 
n ot treate d; s u bjects ra n d o mize d a n d treate d; a n d o verall. A se parate set of ta b ulati o ns are ma de 
f or s u bjects e nr olle d b ut n ot ra n d o mize d.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
9. 4. 2
Pri m ar y  E n d p oi nt( s)
Pri mar y  e n d p oi nt will be a nalyz e d acc or di n g t o pr i mar y esti ma n d. T he c ha n ge fr o m baseli ne 
efficac y e n d p oi nt is a nal yze d o n t he mI T T p o p ulati o n usi n g a  li near  m o del t hat i ncl u des t he 
baseli ne N R S ( 0 - 1 0) val ue f or facial pai n/ press ure/f ull ness as a c o variate, a n d fi xe d effects f or 
treat me nt gr o u p, stratificati o n fact or ( prese nce of nasal p ol y ps ; yes or n o ), sc he d ule d ti me p oi nt, 
a n d ti me p oi nt b y-treat me nt gr o u p i nteracti o n. Ti me p oi nts i ncl u de d i n t he m o del are n o mi nally 
at 1 5, 3 0, 4 5, 6 0, 9 0 a n d 1 2 0 mi n utes p ost -d ose. 
Re peate d meas ures wit hi n s u bject will be m o dele d usi n g t he u nstr uct ure d c o varia nce str uct ure 
f or wit hi n s u bject err or. I n t he case t he m o del fails t o c o n ver ge, a H uy n h -Fel dt err or str uct ure 
will be utilize d, f oll o we d b y a n A R( 1) str uct ure. Err or de grees of free d o m will be calc ulate d 
usi n g t he Ke n war d - R o gers a p pr o xi mati o n if a n u nstr uct ure d c o varia nce str uct ure fits 
a p pr o priatel y;  ot her wise, a sa n d wic h esti mat or will be utilize d t o esti mate t he c o varia nce 
str uct ure, a n d t he de grees of free d o m will be calc ulate d usi n g t he bet wee n-wit hi n met h o d.  
T he differe nce esti mate (ri me ge pa nt - place b o), sta n dar d err or, 9 5 % c o nfi de nce i nter val, a n d p-
val ue will be re p orte d f or 2 h o urs p ost -d ose.
I n t he e ve nt a s u bject uses a n o nst u d y resc ue me dicati o n o n or bef ore 2 h o urs p ost-d ose, all data 
p oi nts after resc ue me dicati o n was a d mi nistere d will be set t o missi n g ( R M = M: Resc ue 
me dicati o n use = Missi n g). Li ke wise, if a s u bject fails t o l o g t heir pai n sc ore after st u d y  dr u g is 
a d mi nistere d, t hr o u g h 2 h o urs p ost- d ose, t his d ata will be c o nsi dere d missi n g ( N C = M: N o n -
c o m pleters = Missi n g).
Se nsiti vit y A n al ysis: T he a nal ys is of t he pri mar y e n d p oi nt ass u mes a h yp ot hetical strate g y  f or 
i nterc urre nt e ve nt of pr o hi bite d resc ue me dicati o n use o n or bef ore 2 h o urs p ost -d ose . It f urther 
ass u mes t hat ha d t he s u bjects n ot use d a resc ue me dicati o n, t heir efficac y  w o ul d ha ve bee n 
si milar t o t he efficac y of s u bjects fr o m t he sa me treat me nt gr o u p w h o di d n ot .  As a res ult, t he 
pr i mar y a nalys is uses a missi n g at ra n d o m ( M A R) strate g y. T he p u r p ose of t hese se nsiti vit y 
a nal ys es is t o i n vesti gate de part ures fr o m t hese ass u m pti o ns.
T he f oll o wi n g se nsiti vit y a nal ys es are pla n ne d:

J u m p t o refere nce

Ti p pi n g P oi nt
All se nsiti vit y  a nalys es are c o n d ucte d o n t he mI T T p o p ulati o n. Details of t hese a nal ys es will be 
disc usse d i n statistical a nal y sis pla n.
9. 4. 3
S e c o n d ar y  E n d p oi nt( s)
Esti ma n ds f or sec o n dar y  e n d p oi nts will be defi ne d i n S A P. A nal y sis of sec o n dar y e n d p oi nts
w o ul d f oll o w t he res pecti ve esti ma n d strate g y .
If t he pri mar y e n d p oi nt test is si g nifica nt, t he n t he sec o n dar y e n d p oi nts are e val uate d usi n g a 
hierarc hical gate -kee pi n g pr oce d ure, wit h eac h test i n t he hierarc h y c o n d ucte d at p = 0. 0 5.  T hese 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
sec o n dar y e n d p oi nts will be teste d i n t he or der s h o w n i n t he Stu d y  O bjecti ves secti o n of t his 
pr ot oc ol. Sec o n dar y e n d p oi nts will be a nal y ze d o n t he mIT T p o p ulati o n. 
T he a nal ys is t o e val uate c ha n ge fr o m baseli ne i n t he T N S S will be d o ne usi n g a  li near  m o del 
t hat i ncl u des t he baseli ne T N S S val ue as a c o variate, a n d fi xe d effects f or treat me nt gr o u p, 
sc he d ule d ti me p oi nt, a n d ti me p oi nt b y-treat me nt gr o u p i nteracti o n. Ti me p oi nts i ncl u de d i n t he 
m o del are n o mi nall y at 1 5, 3 0, 4 5, 6 0, 9 0 a n d 1 2 0 mi n utes p ost -d ose. T he differe nce esti mate 
(ri me ge pa nt - place b o), sta n dar d err or, 9 5 % c o nfi de nce i nter val, a n d p- val ue will be re p orte d f or 
2 h o urs p ost -d ose.
T he a nal ys is t o e val uate c ha n ge fr o m baseli ne i n t he nasal o bstr ucti o n (c o n gesti o n) sc ore o n t he 
N R S ( 0 -1 0) will be d o ne i n t he sa me ma n ner as t he first sec o n dar y  e n d p oi nt, wit h baseli ne nasal 
o bstr ucti o n (c o n gesti o n) sc ore fr o m t he N R S as a c o variate i nstea d of baseli ne T N S S.
T he a nal ys is t o e val uate c ha n ge fr o m baseli ne i n t he nasal disc har ge sc ore o n t he N R S ( 0-1 0) 
will be d o ne i n t he sa me ma n ner as t he first sec o n dar y  e n d p oi nt, wit h baseli ne nasal disc har ge 
sc ore fr o m t he N R S as a c o variate i nstea d of baseli ne T N S S.
T he n u m ber of s u bjects t hat e x perie nce hea dac he pai n relief at 2 h o urs p ost -d ose will be 
a nal yz e d after first i m p uti n g missi n g data at 2 h o urs t o be fail ure (i.e., N C = F: N o n- C o m pleters 
= Fail ure). A d diti o nall y, s u bjects w h o use resc ue me dicati o n o n or bef ore assess me nt of pai n at 2 
h o urs will als o be assi g ne d as fail ures ( R M = F: Resc ue me dicati o n use = Fail ure). T he a nal ys is 
will be d o ne usi n g Ma ntel -Hae ns zel ris k esti mati o n  after i m p utati o n is d o ne, wit h stratificati o n 
b y prese nce of nasal p ol y ps ( y es or n o) . Hea dac he pai n is defi ne d usi n g a 4 -p oi nt scale of n o ne, 
mil d, m o derate, a n d se vere. Hea dac he pai n relief is defi ne d as a hea dac he pai n le vel of n o ne or 
mil d at 2 h o urs p ost -d ose, wit h a hea dac he pai n le vel of m o derate or se vere at baseli ne. N ote t hat 
o nl y  s u bjects wit h a hea dac he pai n le vel of m o derate or se vere at baseli ne will be i ncl u de d i n t his 
a nal ys is. 
T he n u m ber of s u bjects t hat use resc ue me d icati o n at 2 4 p ost-d ose will be a nal yz e d after first 
i m p uti n g missi n g data at 2 4 h o urs t o be fail ure ( N C = F). T he a nalys is will be d o ne usi n g 
M a ntel-Hae nszel ris k esti mati o n after t he missi n g data are i m p ute d as fail ures, wit h stratificati o n 
b y prese nce of nasal p ol y ps ( yes or n o) .
9. 4. 4
A d j u st m e nt f or M ulti pli cit y
T y pe 1 err or is c o ntr olle d t hr o u g h t he use of hierarc hical testi n g.  T he si g nifica nce of t he pri mar y  
e n d p oi nt is e val uate d at t he t w o- si de d al p ha le vel of 0. 0 5.  If t he pri mar y e n d p oi nt is si g nifica nt, 
t he n t he f oll o wi n g sec o n dar y e n d p oi nts will be teste d hierarc hically i n t he or der s pecifie d i n t he 
sec o n dar y o bjecti ves secti o n (Secti o n 2. 2 ), eac h at t he 0. 0 5 le vel. 
T h us, a sec o n dar y  e n d p oi nt will be teste d o nl y if t he prece di n g sec o n dar y e n d p oi nt i n t he 
hierarc h y is deter mi ne d t o be si g nifica nt.  Descri pti ve p -val ues will be pr o vi de d f or a n y n o n -
si g nifica nt sec o n dar y e n d p oi nts a n d c o m parati ve e x pl orat or y e n d p oi nts.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
N o atte m pt will be ma de t o a dj ust f or m ulti plicit y  w he n testi n g t he e x pl orat or y e n d p oi nts. A n y 
e x pl orat or y e n d p oi nts s u bjecte d t o si g nifica nce testi n g are e val uate d at a n u na dj uste d t w o-si de d 
al p ha le vel of 0. 0 5. 
9. 4. 5
Mi s si n g D at a
F or t he pri mar y  e n d p oi nt of c ha n ge i n N R S o n si n us pai n/ press ure/f ull ness fr o m baseli ne, 
s u bjects w h o fail t o rec or d t heir pai n at 2 h o urs p ost-d ose will be c o nsi dere d missi n g ( N C = M); 
t he M M R M a nal ysis m o del will be use d, w hic h ass u mes missi n g data are missi n g at ra n d o m 
( M A R).
T his is t he a p pr oac h f or ha n dli n g missi n g data t hat will als o be use d f or t he first, sec o n d, a n d 
t hir d sec o n dar y e n d p oi nts of c ha n ge fr o m baseli ne i n T N S S, i n N R S f or nasal o bstr ucti o n 
(c o n gesti o n), a n d N R S f or nasal disc har ge, res pecti vel y .
F or t he sec o n dar y  e n d p oi nt of pr o p orti o n of s u bjects wit h hea dac he pai n relief fr o m baseli ne at 2 
h o urs p ost -d ose, missi n g data at 2 h o urs p ost - d ose will be i m p ute d as a fail ure ( N C = F).
F or t he sec o n dar y  e n d p oi nt of pr o p orti o n of s u bjects w h o use resc ue me dicati o n at 2 4 h o urs 
p ost -d ose, missi n g data at 2 4 h o urs p ost -d ose will be i m p ute d as a fail ure ( N C = F).
A d diti o nal met h o ds f or ha n dli n g of missi n g data, i ncl u di n g se nsiti vit y  a nal yses, will be 
des cri be d i n detail i n t he S A P. 
9. 4. 6
R e s c u e M e di c ati o n 
F or t he pri mar y  e n d p oi nt of c ha n ge i n N R S o n si n us pai n/ press ure/f ull ness fr o m baseli ne, t he 
i nterc urre nt e ve nt of use of n o nst u d y resc ue me dicati o ns o n or bef ore t he ti me p oi nt of i nterest ( 2 
h o urs p ost - d ose) will be ha n dle d wit h a h y p ot hetical strate g y . S pecifically,  t he ass u m pti o n will 
be t hat ha d t he s u bject n ot use d a resc ue me dicati o n, t heir efficac y  w o ul d ha ve bee n si milar t o 
t he efficac y of s u bjects fr o m t he sa me treat me nt gr o u p w h o di d n ot use resc ue me dicati o n. T hese 
data p oi nts after resc ue me dicati o n was a d mi nistere d will be set t o missi n g ( R M = M). 
T his is t he a p pr oac h t hat will als o be use d f or ha n dli n g resc ue me dicati o n use o n or bef ore 2 
h o urs p ost - d ose f or t he first, sec o n d, a n d t hir d sec o n dar y e n d p oi nts of c ha n ge fr o m baseli ne i n 
T N S S, i n N R S f or nasal o bstr ucti o n (c o n gesti o n), a n d N R S f or nasal disc har ge, res pecti vel y.
F or t he sec o n dar y  e n d p oi nt of pr o p orti o n of s u bjects wit h hea dac he pai n relief fr o m baseli ne at 2 
h o urs p ost -d ose, s u bjects t hat ta ke resc ue me dicati o n o n or bef ore 2 h o urs p ost-d ose will be 
c o nsi dere d as fail ures ( R M = F). 
Resc ue me dicati o ns are descri be d i n m ore detail i n Secti o n 5. 5.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
9. 4. 7
A n al y si s of S af et y
T he In vesti gat ors deter mi ne t he i n te nsit y of A Es a n d t he relati o ns hi p of A Es t o st u d y t hera p y. 
T he In vesti gat ors’ ter ms are c o de d a n d gr o u pe d b y  s yste m or ga n class usi n g t he latest versi o n of 
t he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) a vaila ble. A Es are prese nte d by 
s yste m or ga n class a n d preferre d ter m, or dere d by t he o verall fre q ue nc y  of e ve nts. If a s u bject 
ha d a n a d verse e ve nt wit h differe nt i nte nsities o ver ti me, t he n o nl y  t he greatest i nte nsit y is 
re p orte d.
A Es are ta b ulate d i n all treate d s u bjects. S A Es occ urri n g i n s ubjects e nr olle d b ut n ot treate d are 
liste d. Deat hs are liste d f or e nr olle d s u bjects wit h o ut re gar d t o o nset.
T he fre q ue ncies of t he f oll o wi n g safet y  e ve nts are s u m marize d b y treat me nt re gi me n, a n d 
o verall, f or treate d s u bjects:  S A Es; all A Es, A Es b y  i nte nsit y; a n d A Es b y relate d ness.
Cli nicall y  si g nifica nt la b orat or y test a b n or malities will be i de ntifie d as Gra de 3 t o 4 la b orat or y 
test res ults gra de d acc or di n g t o n u meric la b orat or y test criteria i n C o m m o n Ter mi n ol o g y Criteria 
f or A d verse E ve nts ( C T C A E) Versi o n 5. 0 ( 2 0 1 7), if a vaila ble. Ot her wise, if C T C A E gra des are 
n ot a vaila ble, t he n res ults will be gra de d acc or di n g t o n u meric la b orat or y  test criteria i n Di visi o n 
of AI D S ( D AI D S) Ta ble f or Gra di n g t he Se verit y of A d ult a n d Pe diatric A d verse E ve nts 
C orrecte d Versi o n 2. 1 ( 2 0 1 7). If a s u bject has a la b orat or y  test a b n or malit y wit h differe nt 
t o xicit y gra des o ver ti me, t he n o nl y t he hi g hest t o xicit y gra de will be re p orte d.
F urt her safet y a nal ys es will be descri be d i n t he statistical a nal ysis pla n.
9. 5
S c h e d ul e of A n al y s e s
T he data fr o m t his st u d y  ma y be l oc ke d a n d a nalyze d at a n y p oi nt after t he last s u bject c o m pletes 
t heir e n d of treat me nt visit a n d a de q uate ti me has bee n all o we d f or f oll o w- u p.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 7 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 0
E T HI C S A N D R E S P O N SI B I LI TI E S
1 0. 1
G o o d Cli ni c al Pr a cti c e
T his st u d y  will be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol, G o o d Cli nical Practice ( G C P), 
G o o d La b orat or y  Practice ( G L P), Inter nati o nal C o nfere nce o n Har m o nizati o n g ui deli nes , a n d all 
a p plica ble re g ulati o ns, i ncl u di n g t he F e deral F o o d, Dr u g a n d C os metic Act, U. S. a p plica bl e 
C o de of Fe deral Re g ulati o ns (title 2 1), a n y  In de pe n de nt Et hics C o m mittee (I E C) re q uire me nts 
relati ve t o cli nical st u dies. T he st u d y will als o be c o n d ucte d i n c o m plia nce wit h t he 
rec o m me n dati o ns lai d d o w n i n t he m ost rece nt versi o n of t he Declarati o n of Helsi n ki.
T his st u d y  will be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol. T he pr ot oc ol a n d a ny a me n d me nts 
a n d t he s u bject i nf or me d c o nse nt will recei ve I nstit uti o nal Re vie w B oar d/ I nde pe n de nt Et hics 
C o m mittee (I R B/ I E C) a p pr o val/fa v ora ble o pi ni o n pri or t o i nitiati o n of t he st u d y.   
T he sp o ns or is res p o nsi ble f or e ns uri n g t hat all u p date d rele va nt i nf or mati o n relate d t o t he 
pr ot oc ol be s u b mitte d t o re g ulat or y  a ut h orities a n d In de pe n de nt Et hics C o m mittees i n 
acc or da nce wit h l ocal la ws a n d re g ulati o ns. T his i ncl u d es e x pe dite d re p orti n g of s us pecte d 
u ne x pecte d seri o us a d verse reacti o ns per re g ulat or y  g ui deli nes.
All seri o us breac hes m ust be re p orte d t o Pfizer ( or desi g nee) i m me diately.  A Seri o us breac h is a 
breac h of t he c o n diti o ns a n d pri nci ples of G C P i n c o n necti o n wit h t he st u d y or pr ot oc ol, w hic h is 
li kel y t o affect, t o a si g nifica nt de gree, t he safety or p h y sical or me ntal i nte grity of t he s u bjects 
of t he st u d y  or t he scie ntific val ue of t he st u d y. E xa m ples i ncl u de ( b ut are n ot li mite d t o):

Missi n g, i na de q uate,
or deli n q ue nt i nf or me d c o nse nt.

Ra n d o mizati o n of a s u bject t hat d oes n ot meet ke y eli gi bilit y  criteria.

Fail ure t o wit h dra w a s u bject meeti n g disc o nti n uati o n criteria.

U nre p orte d seri o us a d verse e ve nts.

I m pr o per brea ki n g of t he bli n d.

C o n d ucti n g t he st u d y wit h o ut I R B a p pr o val. 

W or ki n g u n der a n e x pire d me dical lice nse, or a de barre d or dis q ualifie d stat us.

Falsif y i n g researc h or me dical rec or ds.
St u d y  pers o n nel i n v ol ve d i n c o n d ucti n g t his st u d y will be q ualifie d b y e d ucati o n, trai ni n g, a n d 
e x perie nce t o pe rf or m t heir res pecti ve tas k(s). 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
T his st u d y  will n ot use t he ser vices of st u d y pers o n nel w here sa ncti o ns ha ve bee n i n v o ke d or 
w here t here has bee n scie ntific misc o n d uct or fra u d (e. g., l oss of me dical lice ns ure, de bar me nt).
It is t he sp o ns or’s res p o nsi bili t y t o s u b mit t he pr ot oc ol a n d its a me n d me nts (if a n y), a n d t he I C Fs 
t o re g ulat or y a ut h orities w he n necessar y. 
1 0. 2
Di s s e mi n ati o n of Cli ni c al St u d y  D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of stu dies o n w w w .cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E u dra C T/ C TIS, a n d/ or 
w w w . pfizer.c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire ments of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d c o m plete 
ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y  or t he c o u ntr y i n w hic h t he st u d y 
was c o n d ucte d.
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial res ults o n w w w .cli nicaltrials. g o v f or Pfizer-s p o ns ore d i nter ve nti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a pr o d uct, re gar dless of 
t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. T hese res ults are s u b mitte d f or p osti n g 
i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
E u dra C T/ C TI S
Pfizer p osts cli nical trial res ults o n E u dra C T/ C TI S f or Pfizer -s p o ns ore d i nter ve nti o nal st u dies i n 
acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y  E U re q uire me nts.
w w w. pfizer.c o m
Pfizer p osts C S R s y n o pses a n d plai n -la n g ua ge st u d y res ults s u m maries o n w w w. pfizer.c o m f or 
Pfizer -s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he c orres p o n di n g st u d y res ults are 
p oste d t o w w w.cli nicaltrials. g o v . C S R s yn o pses will ha ve pers o nall y i de ntifia ble i nf or mati o n 
a n o n ymize d.
D oc u me nts wit hi n mar keti n g a p plicati o ns
Pfizer c o m plies wit h a p plica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts i ncl u de d i n 
mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y  d oc u me nts a n d C S Rs i ncl u di n g t he 
pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A Ps. Cli nical d oc u me nts will ha ve 
pers o nall y i de ntifia ble i nf or mati o n a n o n y m ize d.
Data s hari n g
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Pfizer pr o vi des researc hers sec ure access t o s u bject-le vel data or f ull C S Rs f or t he p ur p oses of 
“ b o na-fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of t he disease, 
tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 1 8 m o nt hs after st u d y  
c o m pleti o n. S u bject -le vel data will be a n o ny m ize d i n acc or da nce wit h a p plica ble pri vac y la ws 
a n d re g ulati o ns. C S Rs will ha ve pers o nall y i de ntifia ble i nf or m ati o n a n o n y mize d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal y ses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot be 
pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals re q uesti n g 
access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 3
I n stit uti o n al R e vi e w B o ar d/I n d e p e n d e nt Et hi c s C o m mitt e e
T he I n vesti gat ors a gree t o pr o vi de t he I R B/I E C wit h all a p pr o priate d oc u me nts, i ncl u di n g a c o py 
of t h e pr ot oc ol/a me n d me nts, IC Fs, a d vertisi n g te xt (if a n y ), I n vesti gat or’s br oc h ure (if a ny) a n d 
a n y ot her writte n i nf or mati o n pr o vi de d t o st u d y s u bjects. T he trial will n ot be gi n u ntil t he 
I n vesti gat ors ha ve o btai ne d t he I R B/I E C fa v ora ble writte n a p pr o vals f or t he a b o ve-me nti o ne d 
st u d y d oc u me nts. 
I n t he e ve nt t hat t he pr ot oc ol is a me n de d, t he re vise d pr ot oc ol m ust be a p pr o ve d b y t he I RB/ I E C 
pri or t o its i m ple me ntati o n, u nless t he c ha n ges i n v ol ve o nl y  l o gistical or a d mi nistrati ve as pects 
of t he trial. 
1 0. 4
I nf or me d C o n s e nt
I n vesti gat ors m ust e ns ure t hat s u bjects, or, i n t h ose sit uati o ns w here c o nse nt ca n n ot be gi ve n by 
s u bjects, t heir le gally acce pta ble re prese ntati ves, are clearl y a n d f ull y i nf or me d a b o ut t he 
p ur p ose, p ote ntial ris ks, a n d ot her critical iss ues re gar di n g cli nical st u dies i n w hic h t he y  
v ol u nteer t o partici pate. 
Pfizer ( or desi g nee) will pr o vi de t he In vesti gat or wit h a n a p pr o priate (i.e., Gl o bal or L ocal) 
sa m ple i nf or me d c o nse nt f or m w hic h will i ncl u de all ele me nts re q uire d by I C H, G C P a n d 
a p plica bl e re g ulat or y re q uire me nts.  T he sa m ple i nf or me d c o nse nt f or m will a d here t o t he et hical 
pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki.
Bef ore t he p ote ntial s u bject has u n der g o ne a n y st u d y -relate d scree ni n g pr oce d ures, t he nat ure of 
t he st u d y a n d t he p ote ntial ris ks ass ociate d wit h it will be e x plai ne d t o t he s u bject, a n d t he 
s u bject will be gi ve n a n o p p ort u nit y t o as k q uesti o ns t o his or her satisfacti o n. After t he 
q uesti o ns are a ns were d, b ut bef ore pr ocee di n g f urt her, t he s u bject m ust si g n a n d date an 
I RB/I E C a p pr o ve d writte n i nf or me d c o nse nt f or m f or st u d y . T he si g ne d a n d date d I C F will be 
retai ne d at t he I n vesti gat or’s site, wit h a c o p y pr o vi de d t o t he st u d y s u bject a n d date will be 
e ntere d i n his or her C R F or a p pr o priate s ys te m. T he IR B/I E C m ust re vie w a n d a p pr o ve all 
pr ot oc ol versi o ns a n d i nf or me d c o nse nt f or m versi o ns a n d a c o p y of eac h versi o n of t he I R B/I E C 
a p pr o ve d pr ot oc ol a n d i nf or me d c o nse nt f or m is t o be retai ne d i n t he St u d y  Master file. A n y 
re visi o ns t o t he pr ot oc ol or IC F will be re vie we d a n d a p pr o ve d b y  t he I R B/IE C a n d s u bjects will 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
be i nf or me d of I CF c ha n ge s a n d d oc u me nt c o nti n ui n g c o nse nt b y si g ni n g a n d dati n g t he re vise d 
versi o n of t he I C F.
If a re vise d I C F is i ntr o d uce d d uri n g t he st u dy, eac h s u bject’s f urt her c o nse nt m ust be o btai ne d. 
T he ne w versi o n of t he I C F m ust be a p pr o ve d b y t he IR B/I E C, pri or t o s u bse q ue ntl y  o btai ni n g 
eac h s u bject’s c o nse nt. 
If i nf or me d c o nse nt is i nitiall y gi ve n by a s u bject’s le gal g uar dia n or le gall y acce pta ble 
re prese ntati ve, a n d t he s u bject s u bse q ue ntly bec o mes ca pa ble of ma ki n g a n d c o m m u nicati n g 
t heir i nf or me d c o nse nt d uri n g t he st u d y, t he n t he c o nse nt m ust a d diti o nall y be o btai ne d fr o m t he 
s u bject. 
T he i nf or me d c o nse nt f or m m ust als o i ncl u de a state me nt t hat Pfizer a n d its re prese ntati ves a n d 
re g ulat or y a ut h orities ma y ha ve direct access t o s u bject rec or ds.  
1 0. 5
C a s e R e p ort F or m s
A n In vesti gat or is re q uire d t o pre pare a n d mai ntai n a de q uate a n d acc urate case hist ories desi g ne d 
t o rec or d all o bser vati o ns a n d ot her data perti ne nt t o t he i n vesti gati o n of eac h st u d y patie nt. Data 
re p orte d o n t he C R F t hat are deri ve d fr o m s o urce d oc u me nts m ust be c o nsiste nt wit h t he s o urce 
d oc u me nts or t he discre pa ncies m ust be e x plai ne d.
Electr o nic C R Fs will be pre pare d f or all data c ollecti o n fiel ds w he n E D C is bei n g use d.   
T he c o nfi de ntialit y of rec or ds t hat c o ul d i de ntif y patie nts m ust be pr otec te d, res pecti n g t he 
pri vac y  a n d c o nfi de ntialit y r ules i n acc or da nce wit h t he a p plica ble re g ulat or y re q uire me nt(s). 
T he In vesti gat or m ust retai n a c o p y of t he C R Fs i ncl u di n g rec or ds of c ha n ges a n d c orrecti o ns.   
If E D C is bei n g use d, si g nat ures will be o btai ne d electr o nicall y a n d a c o py of t he electr o nic 
C R Fs will be pr o vi de d ( or t he data fr o m t he C R Fs) f or f ut ure refere nce.
1 0. 6
S p o n s or’ s M e di c all y  Q u alifi e d I n di vi d u al 
T he c o ntact i nf or mati o n f or t he s p o ns or’s M QI f or t he st u d y  is d oc u me nte d i n t he st u d y c o ntact 
list l ocate d i n t he I nvesti gat or Site File.
T o facilitate access t o t heir i n vesti gat or a n d t he s p o ns or’s M QI f or st u d y relate d me dical 
q uesti o ns or pr o ble ms fr o m n o nst u d y  healt hcare pr ofessi o nals, s u bjects are pr o vi de d wit h a n 
E C C at t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr ot oc ol a n d st u d y 
i nter ve nti o n i de ntifiers, ( b) s u bject’s st u d y i de ntificati o n n u m ber, (c) site e mer ge nc y  p h o ne 
n u m ber acti ve 2 4 h o urs/ da y , 7 da ys per wee k, a n d ( d) Pfizer Call Ce nter n u m ber.T he E C C is 
i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he s u bject
a n d t heir i n vesti gat or a n d site staff, a n d bet wee n t he i n vesti gat or a n d s p o ns or st u d y  tea m. T he 
E C C is o nl y  t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n t he researc h st u d y, as a mea ns 
of reac hi n g t he i n vesti gat or or site staff relate d t o t he car e of a s u bject. T he Pfizer Call Ce nter 
n u m ber is t o be use d w he n t he i n vesti gat or a n d site staff are u na vaila ble. T he Pfizer Call Ce nter 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
n u m ber is n ot f or use b y t he s u bject directl y;  if a s u bject calls t hat n u m ber directl y, t he y will be 
directe d bac k t o t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 1
R E C O R D S M A N A G E M E N T
I n acc or da nce wit h t he pri nci ples of G C P a n d G LP, t he st u d y  ma y be i ns pecte d b y re g ulat or y 
a ut h orities, t he sp o ns or a n d C R O. T he s p o ns or is e ntitle d t o access i nf or mati o n a b o ut t he stat us 
of t he st u d y a n d t o re vie w t he ori gi nal d oc u me nts of t he st u d y.
T he In vesti gat or m ust retai n all st u d y  rec or ds a n d s o urce d oc u me nts f or t he ma xi m u m ti me 
peri o d re q uire d b y t he a p plica ble re g ulati o ns a n d g ui deli nes, or i nstit uti o n pr oce d ures or f or t he 
peri o d of ti me s pecifie d b y  t he sp o ns or, w hic he ver is l o n ger.  T he In vesti gat or m ust c o ntact t he 
sp o ns or pri or t o destr o yi n g a n y rec or ds ass ociate d wit h t his st u d y. 
Pfizer will n otif y  t he i n vesti gat ors w he n t he st u d y files f or t his st u d y are n o l o n ger nee de d. 
If t he In vesti gat or wit h dra ws fr o m t he st u d y (i.e., retire me nt, rel ocati o n), t he rec or ds s hall be 
tra nsferre d t o a m ut ually a gree d u p o n desi g nee.  N otice of s uc h tra nsfer will be gi ve n i n writi n g 
t o Pfizer. 
It is t he res p o nsi bilit y of t he In vesti gat or t o e ns ure t hat t he c urre nt dis p ositi o n rec or d of 
i n vesti gati o nal pr o d uct ( ma y be s u p plie d b y t he sp o ns or) is mai ntai ne d at eac h st u d y site w here 
t he st u d y dr u g is i n ve nt orie d a n d dis pe nse d.  Rec or ds or l o gs m ust c o m ply wit h a p plica ble 
re g ulati o ns a n d g ui deli nes a n d s h o ul d i ncl u de:

am o u nt of st u d y  dr u g recei ve d a n d place d i n st ora ge area

la bel I D n u m ber or batc h n u m ber or Kit n u m ber as s pecifie d f or t he pr ot oc ol

a m o u nt dis pe nse d t o a n d ret ur ne d fr o m eac h patie nt

a m o u nt tra nsferre d t o a n ot her area or site f or dis pe nsi n g or st ora ge if a p plica ble

a m o u nt of dr u g l ost or waste d

a m o u nt destr o ye d at t he site if a p plica ble

a m o u nt ret ur ne d t o t he sp o ns or, if a p plica ble

retai n sa m ples f or bi oa vaila bilit y/ bi oe q ui vale nce, if a p plica ble

rec or d of dates a n d i nitials of pers o n nel res p o nsi ble f or I P dis pe nsi n g a n d acc o u nta bilit y    
1 1. 1
S o ur c e D o c u m e nt ati o n
A n I n vesti gat or is re q uire d t o pre pare a n d mai ntai n a de q uate a n d acc urate case hist ories desi g ne d 
t o rec or d all o bser vati o ns a n d ot her data perti ne nt f or all s u bjects o n st u d y.  
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L
If s o urce d oc u me nts are create d t o s u p p ort t he c ollecti o n of st u d y  i nf or mati o n, t his m ust be 
retai ne d wit h t he ot her perti ne nt me dical rec or ds f or eac h s u bject f or verificati o n of data p oi nts, 
u nless ot her wise i nstr ucte d b y  t he sp o ns or or desi g nee t o e nter data directl y o n t he e C R F.
St u d y  m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d i nt o 
t he C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d; a n d t hat t he st u d y  is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  a gree me nts, 
I C H G C P, a n d all a p plica ble re g ulat or y re q uire me nts.
T he In vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/I E C re vie w, a n d re g ulat or y 
a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts.
1 1. 2
St u d y Fil e s a n d R e c or d R et e nti o n
T he sp o ns or d oes n ot re q uire ori gi nal d oc u me nts t hat ha ve alrea d y bee n sca n ne d a n d e ntere d i nt o 
t he e T M F sys te m t o be f or war de d to t he sp o ns or. A n y  ori gi nal d oc u me nts (i.e., 1 5 7 2, si g ne d 
fi na ncial discl os ure, si g ne d IC F, etc.) will be retai ne d i n t he re g ulat or y  bi n der at t he st u d y site. 
T he C R O will c o n d uct a fi nal T M F rec o nciliati o n t o e ns ure all st u d y  files a n d re g ulat or y 
d oc u me nt s ha ve bee n c orrectly u pl oa de d t o t he T M F pri or t o t he cl ose or ter mi nati o n of t he 
st u d y. A ny materials or d oc u me nts t o s u p p ort t he cli nical trial o utsi de of t he e T M F (i.e., rater 
trai ni n g ta pes) s h o ul d be mai ntai ne d b y t he C R O. T he s p o ns or will be c o ntacte d t o deter mi ne 
w het her t he st u d y d oc u me nts/ materials t hat are retai ne d o utsi de of t he T M F will be f or war de d t o 
t he sp o ns or, destr o ye d or ke pt at t he C R O or at a n ot her facilit y f or a l o n ger peri o d of ti me at t he 
sp o ns or ’s e x pe nse.
T he C R O will mai ntai n a de q uate st u d y rec or ds after c o m pleti o n or ter mi nati o n of st u d y. After 
t hat peri o d, t he sp o ns or will be c o ntacte d t o deter mi ne w het her t he st u d y  rec or ds will be 
f or war de d t o t he sp o ns or, destr o y e d or ke pt at C R O or at a n ot her facilit y f or a l o n ger peri o d of 
ti me at t he sp o ns or ’s e x pe nse.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 2
A M E N D M E N T S
Pr ot oc ol m o dificati o ns, e xce pt t h ose i nte n de d t o re d uce i m me diate ris k t o st u d y  s u bjects, ma y be 
ma de o nl y  b y Pfizer ( or s pecifie d desi g nee). A pr ot oc ol c ha n ge i nte n de d t o eli mi nate a n a p pare nt 
i m me diate hazar d t o su bjects ma y  be i m ple me nte d i m me diatel y.
A n y  per ma ne nt c ha n ge t o t he pr ot oc ol m ust be ha n dle d as a pr ot oc ol a me n d me nt. T he writte n 
a me n d me nt m ust be s u b mitte d t o t he I R B/I E C a n d t he In vesti gat or m ust a wait a p pr o val bef ore 
i m ple me nti n g t he c ha n ges. Pfizer or s pecifie d desi g nee will s u b mit pr ot oc ol a me n d me nts t o t he 
a p pr o priate re g ulat or y a ut h orities f or a p pr o val.
If i n t he j u d g me nt of t he I R B/I E C, t he In vesti gat or, a n d/ or Pfizer , t he a me n d me nt t o t he pr ot oc ol 
s u bsta ntiall y c ha n ges t he st u d y desi g n a n d/ or increases t he p ote ntial ris k t o t he s u bject a n d/ or has 
a n i m pact o n t he s u bject ’s i n v ol ve me nt as a st u d y s u bject, t he c urre ntl y a p pr o ve d writte n 
i nf or me d c o nse nt f or m will re q uire si milar m o dificati o n. I n s uc h cases, i nf or me d c o nse nt will be 
re ne we d f or s u bjects e nr olle d i n t he st u d y bef ore c o nti n ue d partici pati o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 3
P U B LI C A TI O N P O LI C Y
T he p u blicati o n p olic y  of Pfizer is disc usse d i n t he In vesti gat or ’s Cli nical Researc h A gree me nt.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 4
S T U D Y DI S C O N TI N U A TI O N 
B ot h Pfizer a n d t he Pri nci pal In vesti gat or reser ve t he ri g ht t o ter mi nate t he st u d y at t he 
In vesti gat or’s site at a n y  ti me. S h o ul d t his be necessar y, Pfizer or a s pecifie d desi g nee will 
i nf or m t he a p pr o priate re g ulat or y a ut h orities of t he ter mi nati o n of t he st u d y a n d t he reas o ns f or 
its ter mi nati o n, a n d t he Pri nci pal I n vesti gat or will i nf or m t he IR B/I E C of t he sa me. I n 
ter mi nati n g t he st u dy, Pfizer a n d t he Pri nci pal I n vesti gat or will ass ure t hat a de q uate 
c o nsi derati o n is gi ve n t o t he pr otecti o n of t he s u bjects’ i nterests.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 8 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 5
D A T A  P R O T E C TI O N
All parties will c o m pl y wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n of 
or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of s u bject data.
S u bject s’ pers o nal data will be st ore d at t he st u d y site i n e ncr ypte d electr o nic a n d/ or pa per f or m 
a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y a ut h orize d st u d y 
staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d or ga nizati o nal 
meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t h e e ve nt of disaster. I n t he e ve nt of 
a p ote ntial pers o nal data breac h, t he st u d y  site will be res p o nsi ble f or deter mi ni n g w het her a 
pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g breac h n otificati o ns as re q uire d b y 
la w.
To  pr otect t he ri g hts a n d free d o ms of s u bjects wit h re gar d t o t he pr ocessi n g of pers o nal data, 
s u bjects will be assi g ne d a si n gle, s u bject-s pecific n u merical c o de. A n y s u bject rec or ds or data 
sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical c o de; s u bject n a mes will n ot be 
tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he s p o ns or will be i de ntifie d b y  t his si n gle, 
s u bject-s pecific c o de. T he st u d y  site will mai ntai n a c o nfi de ntial list of s u bjects w h o partici pate d 
i n t he st u d y, li n ki n g eac h s u bject’s n u merical c o de t o t heir act ual i de ntit y a n d me dical rec or d I D. 
I n case of data tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntiality of s u bjects’ pers o nal data 
c o nsiste nt wit h t he cli nical st u d y  a gree me nt a n d a p plica ble pri vac y la ws.
I nf or mati o n tec h n olo g y  s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are sec ure d 
b y  tec h nical a n d or ga nizati o nal sec urit y meas ures desi g ne d t o pr otect s uc h data a gai nst 
acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access.
T he s p o ns o r mai ntai ns S O Ps o n h o w t o res p o n d i n t he e ve nt of u na ut h orize d access, use, or 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
W he n s u bject data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h data are 
pr o m ptl y  a n d irre v oca bl y deleted fr o m all s y ste ms.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 6
A P P E N DI C E S
1 6. 1
A P P E N DI X I : Str o n g I n hi bit or s a n d Str o n g a n d M o d e rat e I n d u c er s of 
C Y P 3 A 4 P r ot ei n ( N ot all-i n cl u si v e)
T he f oll o wi n g me dicati o ns a n d me dicati o n c o m bi nati o ns are s o me of t he str o n g i n hi bit ors of 
C Y P 3 A 4). T his list s h o ul d n ot be c o nsi dere d all -i ncl usi ve. As descri be d i n t he st u d y pr ot oc ol, 
c o nc o mita nt use of str o n g C Y P 3 A 4 i n hi bit ors is pr o hi bite d. I n di vi d ual dr u g la bels s h o ul d be 
re vie we d f or s pecific i nf or mati o n o n pr o pe nsit y t o i n hi bit C Y P 3 A 4 e nz ymes f or a s pecific 
c o m p o u n d.
Str o n g C Y P 3 A 4 i n hi bit ors
b oce pre vir, c o bicistat, c o ni va pta n, da n o pre vir a n d rit o na vir, el vite gra vir a n d rit o na vir, 
i n di na vir a n d rit o na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir a n d rit o na vir, parita pre vir a n d 
rit o na vir a n d ( o m bitas vir a n d/ or dasa b u vir), p osac o naz ole, rit o na vir, sa q ui na vir a n d rit o na vir, 
tela pre vir, ti pra na vir a n d rit o na vir, tr olea n d o myci n, v oric o naz ole, clarit hr o m yci n, 
nefaz o d o ne, nelfi na vir , mife prist o ne, mi befra dil.  
T he f oll o wi n g me dicati o ns a n d s u p ple me nts are m o derate t o str o n g i n d ucers of C Y P 3 A 4. As 
descri be d i n t he st u d y pr ot oc ol, c o nc o mita nt use of m o derate t o str o n g C Y P 3 A 4 i n d ucers is 
pr o hi bite d. T his list s h o ul d n ot be c o nsi dere d all-i ncl usi ve. I n di vi d ual pr o d uct la bels s h o ul d be 
re vie we d f or s pecific i nf or mati o n o n pr o pe nsit y t o ca use m o derate t o str o n g i n d ucti o n of t he 
C Y P 3 A 4 e nz y me f or a s pecific c o m p o u n d.
Str o n g C Y P 3 A 4 i n d ucers
a pal uta mi de, car ba maze pi ne, p he n o bar bital, p he n yt oi n, rifa m pi n, rifa pe nti ne, St. J o h n’s W ort
M o der ate C Y P 3 A 4 i n d ucers
B ose nta n, rifa b uti n, m o dafi nil, nafcilli n, efa vire nz, etra viri ne, l o pi na vir
Res o urces: 
htt ps:// w w w.f da. g o v/ Dr u gs/ De vel o p me nt A p pr o val Pr ocess/ De vel o p me nt Res o urces/ Dr u gI nteracti
o ns L a beli n g/ uc m 0 9 3 6 6 4. ht m #ta ble 3 - 2
htt ps:// w w w.f da. g o v/ Dr u gs/ De vel o p me nt A p pr o val Pr ocess/ De vel o p me nt R es o urces/ Dr u gI nteracti
o ns L a beli n g/ uc m 0 9 3 6 6 4. ht m #ta ble 3 - 3
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Hac ha d H, Ra g ue nea u -Majlessi I , Le v y R H. A usef ul t o ol f or dr u g i nteracti o n e val uati o n: t he 
U ni versit y  of Was hi n gt o n Meta b olis m a n d Tra ns p ort Dr u g I nteracti o n Data base. H u m 
Ge n o mics. 2 0 1 0 Oct; 5( 1): 6 1- 7 2. 
U ni versit y  of Was hi n gt o n Meta b olis m a n d Tra ns p ort Dr u g I nteracti o n Data base accessi ble at 
htt ps:// w w w. dr u gi nteracti o ni nf o. or g/
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 6. 2
A P P E N DI X II: E C G Fi n di n g s of P ot e nti al Cli ni c al C o n c er n
E C G Fi n di n gs T h at M a y
Q u alif y as A Es

Mar ke d si n us bra d yc ar dia (rate < 4 0 b p m) lasti n g mi n utes.

Ne w P R i nter val pr ol o n gati o n > 2 8 0 ms.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 ms (a bs ol ute).

Ne w pr ol o n gati o n of Q Tc F b y > 6 0 ms fr o m baseli ne.

Ne w -o nset atrial fl utter or fi brillati o n, wit h c o ntr olle d ve ntric ular res p o nse rate: ie,
rate < 1 2 0 b p m.

Ne w -o nset t y pe I sec o n d-de gree ( We nc ke bac h) A V bl oc k of > 3 0 -sec o n d d urati o n.

Fre q ue nt P V Cs, tri plets, or s h ort i nter vals ( < 3 0 sec o n ds) of c o nsec uti ve ve ntric ular 
c o m ple xes.
E C G Fi n di n gs T h at M a y
Q u alif y as S A Es

Q Tc F pr ol o n gati o n > 5 0 0 ms.

A bs ol ute val ue of Q Tc F > 4 5 0 ms A N D Q Tc F c ha n ge fr o m baseli ne > 6 0 ms.

Ne w S T -T c ha n ges s u g gesti ve of m y ocar dial isc he mia.

Ne w -o nset L B B B ( Q R S c o m ple x > 1 2 0 ms).

Ne w -o nset ri g ht b u n dle bra nc h bl oc k ( Q R S c o m ple x > 1 2 0 ms).

S y m pt o matic bra d y car dia. 

As y st ole
o
I n a wa ke, s y m pt o m -free s u bjects i n si n us r h yt h m, wit h d oc u me nte d asys t olic 
pa uses ≥3 sec o n ds or a n y esca pe rate < 4 0 b p m, or wit h a n esca pe r h yt h m t hat 
is bel o w t he A V n o de;
o
I n a wa ke, sy m pt o m -free s u bjects wit h atrial fi brillati o n a n d bra dyc ar dia wit h 
1 or m or e as ys t olic pa uses of at least 5 sec o n ds or l o n ger. 

Atrial fl utter or fi brillati o n, wit h ra pi d ve ntric ular res p o nse rate: ra pi d = rate 
> 1 2 0 b p m.

S ustai ne d s u pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) (“s ustai ne d” = s h ort d urati o n 
wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute).

Ve ntric ular r h yt h ms > 3 0 sec o n d d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m ( H R < 4 0 
b p m), accelerate d i di o ve ntric ular r h yt h m ( H R 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h y car dia ( H R > 1 0 0 b p m [s uc h as t orsa des 
de p oi ntes]).

T y pe II sec o n d- de gree ( M o bitz II) A V bl oc k.

C o m plete (t hir d -de gree) heart bl oc k.
E C G Fi n di n gs T h at Q u alif y as S A Es

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n. 

S ustai ne d ve ntric ular tac h y arr h yt h mias ( > 3 0-sec o n d d urati o n).

Sec o n d - or t hir d -de gree A V bl oc k re q uiri n g pace ma ker place me nt.

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n ve sti gat or, a ny arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he maj or e ve nts of p ote ntial cli nical c o ncer n liste d a b o ve are rec o m me n de d as “alerts” or n otificati o ns fr o m 
t he c ore E C G la b orat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be c o nsi dere d as all -i ncl usi ve of 
w hat is t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 6. 3
A P P E N DI X III : C o ntr a c e pti v e a n d B arri er G ui d a n c e 
1 6. 3. 1
M al e S u bj e ct R e pr o d u cti v e I n cl u si o n Crit eri a
N o c o ntrace pti o n met h o ds are re q uire d f or male s u bjects i n t his st u d y, as t he calc ulate d safety 
mar gi n is ≥1 0 0 f ol d bet wee n t he esti mate d mater nal e x p os ure d ue t o se mi nal tra nsfer a n d t he 
N O A E L  f or seri o us ma nifestati o ns of de vel o p me ntal t o xicit y i n n o ncli nical st u dies.
1 6. 3. 2
F e m al e S u bj e ct R e pr o d u cti v e I n cl u si o n C rit eri a
T he criteria bel o w are part of I ncl usi o n Criteri o n 2. b ( A ge a n d Se x; Secti o n 5. 2 ) a n d s pecif y t he 
repr o d ucti ve re q uire me nts f or i ncl u di n g fe male s u bjects. Refer t o Secti o n 1 6. 3. 4 f or a c o m plete 
list of c o ntrace pti ve met h o ds per mitte d i n t he st u d y. 
A fe male s u bject is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g a n d at least 1 of 
t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o ns bel o w i n Secti o n 1 6. 3. 3 ).
O R

Is a W O C B P a n d a grees t o use a n acce pta ble c o ntrace pti ve met h o d d uri n g t he 
i nter ve nti o n peri o d (f or a mi ni m u m of 2 8 da y s after t he last d ose of st u d y i nter ve nti o n).  
T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n 
relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d pre g na nc y .
1 6. 3. 3
W o m a n of C hil d b e ari n g P ot e nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me norr hea or oli g o me n orr hea) a n d a me nstr ual c y cle ca n n ot be 
c o nfir me d bef ore t he first d ose of st u d y  i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be c o nsi dere d.
Wo me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me narc hal.
2.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g: 

D oc u me nte d h ys terect o m y

D oc u me nte d bilateral sal pi n gect o m y
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 5 of 1 0 4
P FI Z E R C O N FI D E N TI A L

D oc u me nte d bilateral o o p h orect o m y
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a me dical ca use ot her t ha n t he a b o ve (e g, 
m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y ), i n vesti gat or discreti o n s h o ul d be a p plie d t o 
deter mi ni n g st u d y e ntr y.
N ote: D oc u me ntati o n f or a n y  of t he a b o ve cate g ories ca n c o me fr o m t he site pers o n nel’s re vie w 
of t he s u bject ’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y i nter vie w. T he met h o d
of d oc u me ntati o n s h o ul d be rec or de d i n t he s u bject’s me dical rec or d f or t he st u d y.
3.
P ost me n o pa usal fe male:

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n alter nati ve 
me dical ca use. I n a d diti o n:

A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars of a ge a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A fe male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use 
o ne of t he hi g hl y effecti ve n o nestr o ge n h or m o nal c o ntrace pti o n met h o ds if s he 
wis hes t o c o nti n ue her H R T d uri n g t he st u d y. Ot her wise, s he m ust disc o nti n ue H R T 
t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y e nr oll me nt.
1 6. 3. 4
C o ntr a c e pti o n M et h o d s
C o ntrace pt i ve use by me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat Ha ve L o w User De pe n de nc y  
1.
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
2.
I ntra uteri ne de vice.
3.
I ntra uteri ne h or m o ne-releasi n g sys te m.
4.
Bilateral t u bal occl usi o n.
5.
Vasect o mize d part ner:

Vasect o mize d par t ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he W O C B P a n d t he a bse nce of s per m has bee n 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 6 of 1 0 4
P FI Z E R C O N FI D E N TI A L
c o nfir me d. If n ot, a n a d diti o nal hi g hl y  effecti ve met h o d of c o ntrace pti o n s h o ul d be 
use d. T he s per mat o ge nesi s c ycle is a p pr o xi matel y 9 0 da ys.
Hi g hl y Effecti ve Met h o ds T hat Are User De pe n de nt 
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n:

Oral

I ntra va gi nal

Tra ns der mal
7.
Pr o gest o ge n - o nly h or m o ne c o ntr ace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral

I njecta ble
8.
Se x ual A bsti ne nce

Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual lifestyl e of t he 
s u bject.
Ot her Effecti ve Met h o ds
9.
Pr o gest o ge n - o nly oral h or m o nal c o ntrace pti o n w here i n hi biti o n of o v ulati o n is n ot t he 
pri mar y  m o de of acti o n.
1 0. Male or fe male c o n d o m, wit h or wi t h o ut s per mici de.
1 1. Cer vical ca p, dia p hra g m, or s p o n ge wit h s per mici de.
1 2. A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m, or s p o n ge wit h 
s per mici de ( d o u ble-barrier met h o ds).
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 7 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 6. 4
A P P E N DI X I V: Pr ot o c ol Am e n d m e nt Hi st or y
T he pr ot oc ol a me n d me nt s u m mar y  of c ha n ges ta ble f or t he c urre nt a me n d me nt is l ocate d 
directl y  bef ore t he St u d y s u m mar y. T he pr ot oc ol a me n d me nt s u m mar y of c ha n ges ta bles f or past 
a me n d me nt(s) ca n be f o u n d bel o w:
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate
Versi o n 1. 0 – Ori gi nal 
N ot A p plica ble
2 1 Oct 2 0 2 1
Versi o n 2. 0 –
A me n d me nt 1
C orrecte d t he re q uire me nt:  S u bjects m ust ha ve ha d at least t w o 
i nsta nces of facial pai n/ press ure/f ull ness t hat ha d reac he d a c urre nt 
i nte nsit y of m o derate or se vere o n a 4-p oi nt rati n g scale ( 0 = N o ne, 1 
= Mil d, 2 = M o derate, 3 = Se vere) w it hi n 3 0 da ys pri or t o t he 
Scree ni n g Visit.  T his was c orrecte d i n t w o places t hat it a p pears i n 
t he pr ot oc ol b y a d di n g “ or se vere” f oll o wi n g t he w or d “ m o derate”.  
T his w as u p date d i n t he s y n o ps is a n d i n I ncl usi o n 1c.
U p date d t he p o w er calc ulati o n/sa m ple size i n Secti o n 9. 2  t o i ncrease 
t he n u m ber of e val ua ble s u bjects fr o m 1 6 0 t o 2 0 0.
Pri mar y, sec o n dar y, a n d e x pl orat or y o bjecti ves were u p date d t o 
e ns ure c o nsiste nc y i n t he wa y t he y are writte n i n t he s y n o psis a n d 
b o d y of t he pr ot oc ol.
T h e w or d “ac ute” was i nserte d i nt o t he descri pti o n of t he st u d y desi g n 
a n d pri mar y o bjecti ve t o pr o vi de clarit y.  T he st u d y desi g n n o w  rea ds: 
T his is a d o u ble -bli n d, ra n d o mize d, m ultice nter, o ut patie nt e val uati o n 
of t he safet y a n d efficac y of ri me ge pa nt as c o m pare d t o place b o f or 
t he ac ute treat me nt of c hr o nic r hi n osi n usitis ( C R S) wit h or wit h o ut 
nasal p ol y ps.
F oll o w i n g fee d bac k fr o m t he F D A, t he f oll o wi n g se nte nce was a d de d 
t o t he pr ot oc ol: S u bjects s h o ul d ha ve access t o s yste mic 
c ortic oster oi ds a n d a nti bi otics d uri n g t he trial f or treat me nt of 
s y m pt o ms, if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he 
st u d y if t he y recei ve t h ose t hera pies. T his was a d de d t o t he pr ot oc ol 
s y n o psis, Secti o n 4. 2. 2. 1, a n d Secti o n 5.5.
T he te xt “sta ble d osi n g, n ot P R N” was a d de d t o Secti o n 5. 5 f or 
Le u k otrie ne m o difiers a n d Cr o m ol y n.
T he st u d y sc he matic was u p date d t o be m ore c o ncise t o t he st u d y a n d 
f or f or matti n g p ur p oses. Refere nces t o pai n were c ha n ge d t o 
pai n/ press ure/f ull ness.
I n Secti o n 6. 1, Electr o nic C R F I nstr ucti o ns were re m o ve d fr o m t he 
list of st u d y materials.  C R F i nstr ucti o ns are e m be d de d i n t he e C R F.
Wee kl y c o ntact (e. g., p h o ne, te xt, e mail) w as a d de d t o t he st u d y 
bet w ee n t he Baseli ne Visit a n d d osi n g t o m o nit or (a n d re mi n d s u bjects 
2 1 Ja n 2 0 2 1
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 8 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate
t o re p ort) a n y s yste mic c ortic oster oi d a n d/ or a nti bi otics ( ot her t ha n 
t o pical nasal a nti bi otics) use. T his was a d de d t o Ta ble 1 B H V 3 0 0 0 -
3 1 6 Sc he d ule of Assess me nts a n d Secti o n 6. 2. 6.
F S H, H b A 1c a n d Li pi d pa nel were a d de d t o Ta ble 1 B H V 3 0 0 0 -3 1 6 
Sc he d ule of Assess me nts a n d Secti o n 6. 2. 4. 1.  
Ta ble 1 B H V 3 0 0 0 -3 1 6 Sc he d ule of Assess me nts was u p date d t o 
clarif y a n d c orrect t he c o m me nts f or t he C -S S R S a n d t he S N O T -2 2 
pr oce d ures.
T he f oll o w i n g e xcl usi o n criteria were u p date d t o eit her c orrect or 
clarif y w hat was writte n or t o a d d c o nsiste nc y wit h ot her as pects of 
t he pr ot oc ol: 1f, 4a, 6a, a n d 6i.
I n Secti o n 5. 4 Pr o hi bite d a n d Restricte d C o nc o mita nt Me dicati o ns 
wa s u p date d.  N u m ber 3 i n t he list descri bi n g s yste mic c ortic oster oi ds 
wa s u p date d a n d a descri pti o n of pr o hi bite d a nti bi otics was a d de d t o 
be c o nsiste nt wit h t he F D A’s fee d bac k.  
I n Secti o n 6. 4 Earl y Disc o nti n uati o n fr o m t he St u d y, use of s yste mic 
c ortic oster oi ds a n d use of a nti bi otics ( ot her t ha n t o pical nasal 
a nti bi otics) were a d de d t o t he list of reas o ns a s u bject m ust 
disc o nti n ue t he st u d y.
I n secti o n 8. 2. 1 C ollecti o n a n d Re p orti n g of N o n-Seri o us A d verse 
E ve nts, t he se nte nce “ N o n seri o us A E i nf or mati o n s h o ul d als o be 
c ollecte d fr o m t he start of a place b o lea d -i n p hase or ot her o bser vati o n 
peri o d i nte n de d t o esta blis h a baseli ne stat us f or a s u bject.” 
Versi o n 3. 0 –
A me n d me nt 2
T o pical nasal a ntic h oli ner gics were a d de d t o t he list of all o we d resc ue 
me dicati o ns a n d me dicati o ns t hat ma y be ta ke n f or n o n -q ualif yi n g 
C R S ass ociate d facial pai n/ press ure/f ull ness.  T his has bee n a d de d i n 
t he St u d y Desi g n secti o n of t he s y n o psis; Secti o n 4. 2. 2. 1, a n d Secti o n 
5. 5.
Secti o n 5. 2, I ncl usi o n 2. b. w as f urt her clarifie d wit h a d diti o nal te xt:  
Ori gi nal te xt:  Ra di o gra p hic i ma gi n g s h o wi n g i nfla m mati o n of t he 
para nasal si n uses.  Ne w Te xt: Ra di o gra p hic i ma gi n g s h o wi n g 
i nfla m mati o n of t he para nasal si n uses wit h p arti al o p acific ati o n of at 
le ast t w o si n uses or c o m plete o p acific ati o n of at le ast one si n us .
Secti o n 5. 2, I ncl usi o n 2. d. w as u p date d t o clarif y re q uire me nts f or 
dail y use of me dicati o ns.  Ori gi nal Te xt:  S u bject w it h dail y use of 
me dicati o ns t o treat C R S sy m pt o ms ( ple ase refer t o Secti o n 5. 5) is 
per mitte d t o re mai n o n t hera p y if t he y ha v e bee n o n a sta ble d ose f or 
at least 3 m o nt hs pri or t o t he Scree ni n g Visit, a n d t he d ose is n ot 
e x pecte d t o c ha n ge d uri n g t he c o urse of t he st u d y.  Ne w Te xt:  S u bject 
wit h dail y use of me dicati o ns liste d i n Secti o n 5. 5 is per mitte d t o 
r e mai n o n t hera p y if t he y ha ve bee n o n a sta ble d ose f or at least 1 
1 5 Mar 2 0 2 2
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 9 9 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate
m o nt h pri or t o t he Scree ni n g Visit, a n d t he d ose is n ot e x pecte d t o 
c ha n ge d uri n g t he c o urse of t he st u d y.
Secti o n 5. 3, E xcl usi o n 1a w as u p date d t o clarif y t hat i nfre q ue nt 
te nsi o n-t ype hea dac he is n ot e xcl usi o nar y.  T he f oll o w i n g se nte nce 
wa s a d de d:  I nfre q ue nt te nsi o n-t ype hea dac he c o nsiste nt wit h 
dia g n ostic criteria acc or di n g t o t he I C H D -3 is n ot e xcl usi o nar y.
Secti o n 5. 3, E xcl usi o n 1e., n., o., a n d p. w ere u p date d t o clarif y 
e xcl usi o nar y c o nc o mita nt ill nesse s:  
1.e. w as c ha n ge d fr o m S u bject has di a g n ose d or s us pecte d i n vasi ve 
f u n gal r hi n osi n usitis. t o S u bject has a hist ory of i n vasi ve f u n gal 
r hi n osi n usitis.
1. n. w as c ha n ge d fr o m S u bject has a di a g n osis of si n us m uc ocele. t o
S u bject has a hist ory of si n us m ucocele wit hi n 1 ye ar pri or t o t he 
Scree ni n g Visit.
1. o. w as c ha n ge d fr o m S u bject has a di a g n osis of nasal or para nasal 
t u m or. t o S u bject has a hist ory of m ali g n a nt nasal or para nasal t u m or.
1. p. w as c ha n ge d fr o m S u bject has a di a g n osis of o d o nt o ge nic 
si n usitis. t o S u bject has a hist ory of o d o nt o ge nic si n usitis wit hi n 1 
ye ar pri or t o t he Scree ni n g Visit.
Secti o n 5. 3 E xcl usi o n 2. d. clarifies t he defi niti o n of u nc o ntr olle d 
h y perte nsi o n.  T he f oll o wi n g se nte nce was a d de d: A si n gle bl o o d 
press ure me as ure me nt of g re ater t h a n 1 5 0 m m H g syst olic or 1 0 0 
m m H g di ast olic after 1 0 mi n utes of rest is excl usi o n ary.
Secti o n 5. 3 E xcl usi o n 2. g. was u p date d t o a d d t hat s u bjects wit h 
se vere he ptic i m pair me nt ( C hil d-P u g h C) are t o be e xcl u de d. T he 
f oll o wi n g se nte nce was a d de d t o Excl usi o n 2. g: Severe he p atic 
i m p air me nt ( C hil d-P u g h C) is excl usi o n ary i n all c ases .
Secti o n 5. 3 E xcl usi o n 6. g. u p date d t he hist or y of ne w or rece ntl y 
m o difie d le u k otrie ne m o difiers t hera p y. Te xt was c ha n ge d fr o m 
S u bject has a hist or y of ne w or rece ntl y m o difie d le u k otrie ne 
m o difiers t hera p y wit hi n t he 3 m o nt hs pri or t o Scree ni n g Visit. t o
S u bject has a hist or y of ne w or rece ntl y m o difie d le u k otrie ne 
m o difiers t hera p y wit hi n t he 1 m o nt h pri or t o Scree ni n g Visit.
Secti o n 5. 3 E xcl usi o n 6. h. u p date d t he hist or y of ne w or rece ntl y 
m o difie d le u k otrie ne m o difiers t hera p y. Te xt was c ha n ge d fr o m 
S u bject has a hist or y of ne w or rece ntl y m o difie d β -a dre n oce pt or 
a g o nists t hera p y wit hi n t he 3 m o nt hs pri or t o Scree ni n g Visit. t o 
S u bject has a hist or y of ne w or rece ntl y m o difie d β -a dre n oce pt or 
a g o nists t hera p y wit hi n t he 1 m o nt h pri or t o Scree ni n g Visit.
Secti o n 5. 4 Pr o hi bite d a n d Restricte d C o nc o mita nt Me dicati o ns:  # 1 6 
wa s a d de d t o rea d T o pic al n as al dec o n gest a nts s h o ul d n ot b e t ake n 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 0 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate
m ore t h a n 3 ti mes per week.
Secti o n 5. 4 Pr o hi bite d a n d Restricte d C o nc o mita nt Me dicati o ns:  
N u m bers 3, 4 a n d 5 w ere u p date d t o be restricte d pri or t o t he 
Scree ni n g Visit.  F or merl y t he y were restricte d pri or t o t he Baseli ne 
Visit.  See te xt bel o w .
3. S yste mic c ortic oster oi ds (e. g., pre d nis o ne, pre d nis ol o ne, 
met h yl pre d nis ol o ne, beta met has o ne, de xa met has o ne, tria mci n ol o ne, 
h y dr oc ortis o ne, c ortis o ne) s h o ul d n ot be ta ke n 3 0 da ys pri or t o t he 
Scree ni n g Visit a n d t hr o u g h o ut t he st u d y. S u bjects s h o ul d ha ve access 
t o s yste mic c ortic oster oi ds d uri n g t he trial f or treat me nt of s y m pt o ms, 
if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he st u d y if t he y 
recei ve t his t hera p y. 
4. A nti bi otics, ot her t ha n t o pical nasal a nti bi otics, s h o ul d n ot be ta ke n 
1 4 da ys pr i or t o t he Scree ni n g Visit a n d t hr o u g h o ut t he st u d y. S u bjects 
s h o ul d ha ve access t o a nti bi otics d uri n g t he trial f or treat me nt of 
s y m pt o ms, if i n dicate d. H o we ver, s u bjects s h o ul d disc o nti n ue t he 
st u d y if t he y recei ve t his t hera p y.
5. M o n ocl o nal a nti b o d y t h era p y (e. g., d u pil u ma b, me p oliz u ma b, 
o m aliz u ma b, be nraliz u ma b, resliz u ma b) s h o ul d n ot be ta ke n 6 m o nt hs 
pri or t o t he Scree ni n g Visit a n d t hr o u g h o ut t he st u d y.
Secti o n 5. 4:  Para gra p h w as u p date d t o f urt her clarif y t he criteria f or 
dail y use me dicati o ns.  T e xt was u p date d fr o m S u bjects wit h dail y use 
of me dicati o ns t o tre at C R S sy m pt o ms are per mitte d t o re mai n o n 
t hera p y pr o vi de d t he y ha ve bee n o n a sta ble d ose f or at least 3 m o nt hs
pri or t o t he B aseli ne Visit (see Secti o n 5. 5). t o S u bjects wit h dail y use 
of me dicati o ns liste d i n Secti o n 5. 5 are per mitte d t o re mai n o n t hera p y 
pr o vi de d t he y ha ve bee n o n a sta ble d ose f or at least 1 m o nt h pri or t o 
t he Scree ni n g Visit. 
Secti o n 5. 5 Dail y a n d Resc ue Me dicati o ns was u p date d t o re d uce t he 
ti me me dicati o ns m ust be sta ble a n d t o clarif y t hat sali ne, as s pecifie d 
i n t he ne w te xt, ma y be use d wit h u p t o t wo t o pical nasal me dicati o ns.  
I n a d diti o n, t he list of me dicati o ns was u p date d a n d clarifie d. 
Secti o n was u p date d fr o m: S u bjects m ay n ot use m ore t h a n 1 of t he 
f oll o wi n g me dic ati o ns. Me dicati o n d oses m ust be st a ble wit hi n 3 
m o nt hs pri or t o t he B aseli ne Visit a n d t hr o u g h o ut t he st u d y. 
D aily me dic ati o ns t h at are per mitte d d uri n g t he st u dy i ncl u de:

D aily me dic ati o ns t h at are per mitte d d uri n g t he st u dy i ncl u de:

T o pic al n a s al c ortic oster oi ds (s pr ay or ri nse; st a ble d osi n g, n ot 
P R N)

T o pic al n as al a nti bi otics a n d a ntif u n g al me dic ati o ns (s pr ay or 
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 1 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate
ri nse; st a ble d osi n g, n ot P R N)

T o pic al n as al a ntic h oli ner gics (s pr ay or ri nse; st a ble d osi n g, n ot 
P R N)

T o pic al a n d or al a nti hist a mi n es ( n o n -se d ati n g; st a ble d osi n g, n ot 
P R N)

S ali ne (s pr ay or ri nse, a d ditives s uc h as deter ge nts or 
m oist urizers are ok)

Or al dec o n gest a nts (st a ble d osi n g, n ot P R N)

Le uk otrie ne m o difiers (st a ble d osi n g, n ot P R N)

Cr o m oly n (st a ble d osi n g, n ot P R N)

M uc olytics (e. g., acetylcystei ne) (st a ble d osi n g, n ot P R N)
After d osi n g wit h st u d y me dicati o n, all ot her p ai n me dicati o n is 
pr o hi bite d d uri n g t he 2 h o urs p ost -d ose. At t he e n d of 2 h o urs after 
d osi n g wit h st u d y me dicati o n (a n d after t he 2 -h o ur assess me nts ha ve 
bee n c o m plete d o n t he e Diar y), s u bjects w ill be per mitte d t o use t he 
f oll o wi n g resc ue me dicati o n: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y), or 
as piri n, i b u pr ofe n, na pr o xe n ( or a n y ot her t y pe of n o n -ster oi dal a nti-
i nfla m mat or y dr u g ( N S AI D)), oral a nti hista mi nes ( n o n-se dati n g), oral 
dec o n gesta nts, t o pical nasal dec o n gesta nts (all u p t o t he dail y 
rec o m me n de d d ose i n dicate d o n t he dr u g pac ka gi n g). T hese are t he 
o nl y me dicati o ns all o we d f or resc ue treat me nt after 2 h o urs p ost d ose 
of st u d y me dicati o n.  
T o: Me dicati o n d oses m ust be st a ble wit hi n o ne m o nt h pri or t o t he 
Scree ni n g Visit a n d t hr o u g h o ut t he st u d y. S u bjects ma y use:

S ali ne a n d ot her n o n -me dic ate d s pr ay/ri nse ( a d ditives s uc h as 
deter ge nts, m oist urizers, m uc olytics are per mitte d) - m ai nt ai n 
d osi n g re gi me n est a blis he d pri or t o t he Scree ni n g Visit
A N D u p t o t w o of t he t o pic al n as al me dic ati o ns (st a ble d osi n g, n ot 
P R N, a ny i n dic ati o n ):

T o pic al n as al c ortic oster oi ds (s pr ay or ri nse)

T o pic al n as al a nti bi otics a n d a ntif u n g al me dic ati o ns (s pr ay or 
ri nse)

T o pic al n as al a nti hist a mi nes ( n o n -se d ati n g)

T o pic al n as al cr o m oly n
A N D a ny of t he f oll o wi n g me dic ati o ns (st a ble d osi n g, n ot P R N):
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 2 of 1 0 4
P FI Z E R C O N FI D E N TI A L
Versi o n N u m ber
Brief Descri pti o n S u m m ar y of C h a n ges
D ate

Le uk otrie ne m o difiers 

Cr o m oly n ( or al or i n h al ati o n)

Met hylx a nti nes (e. g., t he o p hylli ne, a mi n o p hylli nes) 

M uc o active a ge nts (e. g., g u aife nesi n, acetylcystei ne) 
S u bjects wit h c o nc o mit a nt ast h m a or C O P D m ay re m ai n o n t heir 
b aseli ne S o C tre at me nt if t hey h ave bee n o n a st a ble d ose f or at le ast 
1 m o nt h pri or t o t he Scree ni n g Visit a n d if n ot s pecific ally liste d i n 
S ecti o n 5. 4 Pr o hi bite d a n d Restricte d C o nc o mit a nt Me dic ati o ns, a n d 
t he d ose is n ot ex pecte d t o c h a n ge d uri n g t he c o urse of t he st u dy. 
S u bjects m ay use t heir resc ue i n h alers a n d/ or ne b ulizers as directe d 
by t heir H C P.
After d osi n g wit h st u d y m e dic ati o n, all ot her C R S me dic ati o n is 
pr o hi bite d d uri n g t he 2 h o urs p ost -d ose. At t he e n d of 2 h o urs after 
d osi n g wit h st u d y me dicati o n (a n d after t he 2 -h o ur assess me nts ha ve 
bee n c o m plete d o n t he e Diar y), s u bjects w ill be per mitte d t o use t he 
f oll o wi n g resc ue me dicati on: aceta mi n o p he n ( u p t o 1 0 0 0 m g/ da y), or 
as piri n, i b u pr ofe n, na pr o xe n ( or a n y ot her t y pe of n o n -ster oi dal a nti-
i nfla m mat or y dr u g ( N S AI D)), oral a nti hista mi nes ( n o n-se dati n g), oral 
dec o n gesta nts, t o pical nasal dec o n gesta nts, t o pic al n as al 
a ntic h oli ner gics (all u p t o t he dail y rec o m me n de d d ose i n dicate d o n 
t he dr u g pac ka gi n g). T hese are t he o nl y me dicati o ns all o we d f or 
resc ue treat me nt after 2 h o urs p ost d ose of st u d y me dicati o n.  
Secti o n 8. 4 Pre g na nc y: T his secti o n i nstr ucti n g w here t o e mail t he 
Pre g na nc y F or m  has a t y p o gra p hical err or.  B H V 3 0 0 0-3 1 4 was 
u p date d t o B H V 3 0 0 0 -3 1 6.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 3 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 7
R E F E R E N C E S
1. 
R ose nfel d R M, Piccirill o J F, C ha n drase k har S S, et al. Cli nical practice g ui deli ne 
( u p date): a d ult si n usitis. Ot olar yn g ol Hea d Nec k S ur g 2 0 1 5; 1 5 2: S 1 -S 3 9.
2. 
B hattac har y ya N, Orla n di R R, Gre b ner J, Marti ns o n M. C ost b ur de n of c hr o nic 
r hi n osi n usitis: a clai ms-base d st u d y . Ot olar yn g ol Hea d Nec k S ur g 2 0 1 1; 1 4 4: 4 4 0 - 5.
3.
Se da g hat A R. C hr o nic R hi n osi n usitis. A m Fa m P h ysicia n 2 0 1 7; 9 6: 5 0 0 - 6.
4.
Bac h ert C, Ge vaert P, Helli n gs P. Bi ot hera pe utics i n C hr o nic R hi n osi n usitis wit h a n d 
wit h o ut Nasal P ol y ps. J Aller g y  Cli n I m m u n ol Pract 2 0 1 7; 5: 1 5 1 2- 6.
5.
S ha h S A, I s hi na ga H, Ta ke uc hi K. Pat h o ge nesis of e osi n o p hilic c hr o nic r hi n osi n usitis. J 
I nfla m m ( L o n d) 2 0 16; 1 3: 1 1.
6.
Ha mil os D L . C hr o nic r hi n osi n usitis: e pi de mi ol o g y a n d me dical ma na ge me nt. J Aller g y 
Cli n I m m u n ol 2 0 1 1; 1 2 8: 6 9 3 -7 0 7; q uiz 8 - 9.
7.
F o k ke ns WJ, L u n d VJ, H o p ki ns C, et al. E ur o pea n P ositi o n Pa per o n R hi n osi n usitis a n d 
Nasal P ol y ps 2 0 2 0. R hi n ol o g y  2 0 20; 5 8: 1 -4 6 4.
8.
S u h J D, Ke n ne d y  D W. Treat me nt o pti o ns f or c hr o nic r hi n osi n usitis. Pr oc A m T h orac S oc 
2 0 1 1; 8: 1 3 2 - 4 0.
9.
Ste ve ns W W, Sc hlei mer R P. As piri n -E xacer bate d Res pirat or y  Disease as a n E n d ot ype of 
C hr o nic R hi n osi n usitis. I m m u n ol Aller g y  Cli n N ort h A m 2 0 1 6; 3 6: 6 6 9 - 8 0.
1 0.
B o nfils P, Hali mi P, Mali n va u d D. A dre nal s u p pressi o n a n d oste o p or osis after treat me nt 
of nasal p ol y p osis. Acta Ot olar y n g ol 2 0 0 6; 1 2 6: 1 1 9 5 - 2 0 0.
1 1.
Sat o I , I m ura K, Mi wa Y, Y os hi da S, S u n o hara M. Distri b uti o ns of calcit o ni n ge ne-
relate d pe pti de a n d s u bsta nce P i n t he h u ma n ma xillar y  si n us of Ja pa nese ca da vers. J 
Cra ni o ma xill ofac S ur g 2 0 1 2; 4 0:e 2 4 9 - 5 2.
1 2.
Sat o T, Sasa hara N, Ka n da N, et al. Distri b uti o n of C G R P a n d T R P V 2 i n H u ma n 
Para nasal Si n uses. Cells Tiss ues Or ga ns 2 0 1 7; 2 0 3: 5 5- 6 4.
1 3.
Ra n gi S P, Sa m ple S, Ser w o ns ka M H, Le na ha n G A, G oetzl EJ. Me diati o n of pr ol o n ge d 
i ncreases i n nasal m uc osal bl o o d fl o w b y calcit o ni n ge ne-relate d pe pti de ( C G R P). J Cli n 
I m m u n ol 1 9 9 0; 1 0: 3 0 4-1 0.
1 4.
Bara ni u k J N, Kali ner M A. Ne ur o pe pti des a n d nasal secreti o n. J Aller g y Cli n Im m u n ol 
1 9 9 0; 8 6: 6 2 0 - 7.
1 5.
Bara ni u k J N, L u n d gre n J D, G off J, et al. Calcit o ni n ge ne-relate d pe pti de i n h u ma n nasal 
m uc osa. A m J P h y si ol 1 9 9 0; 2 5 8: L8 1- 8.
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

B H V 3 0 0 0 ( P F -0 7 8 9 9 8 0 1) (ri me ge pa nt)
Pr ot oc ol B H V 3 0 0 0 -3 1 6 ( C 4 9 5 1 0 1 5) 
Fi nal Pr ot oc ol Versi o n 4. 0, A me n d me nt 3, 1 4 J ul y 2 0 2 3
Pa ge 1 0 4 of 1 0 4
P FI Z E R C O N FI D E N TI A L
1 6.
Br o ka w JJ, W hite G W. Calcit o ni n ge ne -relate d pe pti de p ote ntiates s u bsta nce P-i n d uce d 
plas ma e xtra vasati o n i n t he rat trac hea. L u n g 1 9 9 2; 1 7 0: 8 5 - 9 3.
1 7.
Ca m bri d ge H, Brai n S D. Calcit o ni n ge ne -relate d pe pti de i ncreases bl o o d fl o w a n d 
p ote ntiates plas ma pr otei n e xtra vasati o n i n t he rat k nee j oi nt. Br J P har mac ol 1 9 9 2; 1 0 6: 7 4 6 - 5 0.
1 8.
G uar naccia S, Bara ni u k J N, Bella nti J, D ui na M. Calcit o ni n ge ne-relate d pe pti de nasal 
pr o v ocati o n i n h u ma ns. A n n Aller g y  1 9 9 4; 7 2: 5 1 5- 9.
1 9.
Lacr oi x J S, K urt A M, P oc h o n N, Brett o n C, L u n d ber g J M, Des h usses J. Ne utral 
e n d o pe pti dase acti vit y a n d c o nce ntrati o n of se ns ory ne ur o pe pti de i n t he h u ma n nasal m uc osa. 
E ur Arc h Ot or hi n olar y n g ol 1 9 9 5; 2 5 2: 4 6 5 - 8.
2 0.
Bella m y J L,  Ca dy R K, D ur ha m P L . Sali var y le vels of C G R P a n d VIP i n r hi n osi n usitis 
a n d mi grai ne patie nts. Hea dac he 2 0 0 6; 4 6: 2 4 - 3 3.
2 1.
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0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)

D o c u m e nt A p pr o v al R e c or d
D o c u m e nt N a m e:
D o c u m e nt Titl e:
Si g n e d B y:
D at e( G M T)
Si g ni n g C a p a cit y
0 9 0 1 7 7 e 1 9 e 2 9 2 2 5 8\ A p pr o v e d\ A p pr o v e d O n: 2 8- J ul- 2 0 2 3 1 5: 5 7 ( G M T)
P P D
P P D