A Randomized, Double-blind, Placebo-controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Sponsor: Biohaven Pharmaceuticals, Inc.

PROTOCOL TITLE: A randomized, double-blind, placebo-controlled trial ofadjunctive 
Troriluzole in Obsessive Compulsive Disorder
NCT NUMBER: NCT03299166
DATE: 13-Oct-2022

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 1 of 97 
Draft Version 10; 13 Oct 2022 
DRUG: 
Troriluzole (BHV4157) 
STUDY NUMBER(S): 
BHV4157-202 
PROTOCOL(S) TITLE: 
A randomized, double-blind, placebo-controlled trial of 
adjunctive Troriluzole in Obsessive Compulsive Disorder 
IND NUMBER: 
135590 
SPONSOR: 
Biohaven Pharmaceutical Holding Company Limited 
DRAFT ORIGINAL 
PROTOCOL DATE: 
09 Aug 2017 
VERSION NUMBER: 
V10 
Includes Amendment 01, Amendment 02, Amendment 03, 
Amendment 04, Amendment 05,  Amendment 06, 
Amendment 07, Amendment 08, Amendment 09, and 
Administrative Letter 1 dated: 25Aug17 
VERSION DATE: 
13 Oct 2022 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 2 of 97 
 
Draft Version 10; 13 Oct 2022 
 
SUMMARY OF CHANGES 
 
Version Number Brief description summary of changes 
Date 
Version 06 – 
Amendment 01, 
02, 03, 04 and 05 – 
Incorporates 
Admin Letter 01 
The protocol has been updated to clarify that current SOC 
therapy must be monotherapy. 
Section 5.3:  
2p: Added exclusion criteria that women who are pregnant 
or breastfeeding are excluded from study participation.  
4h: Exclusion has been modified to clarify that, in addition 
to herbal medications, use of herbal supplements is 
excluded within 30 days of randomization and during the 
course of the study. 
Section 5.4:  
Added exclusion for use of cannabidiol (CBD) oil.  
Section 9.1.2:  
Revised to allow for IP temperature excursions between 
15°C and 20°C (59°F -68°F) 
Section 11.4.2: 
Added clarification based on FDA reveiwer’s comment. 
Since the primary intent of this trial is to evaluate the 
effect of the drug when taken as intended in the protocol, a 
hypothetical strategy will be employed for the intercurrent 
event of treatment/study discontinuation (due to any 
reason). Specifically, the assumption will be that had the 
subjects not discontinued, their efficacy would have been 
similar to the efficacy of subjects from the same treatment 
group who did not discontinue. For other intercurrent 
events that do not cause treatment/study discontinuation 
such as modest treatment non-compliance, protocol 
allowed dose adjustments, or initiation or adjustment of 
concomitant medications related to other symptoms all 
observed values will be used. 
3 June 2019 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 3 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Version 07 – 
Amendment 01, 
02, 03, 04, 05 and 
06 – Incorporates 
Admin Letter 01 
Version 08 – 
Amendment 01, 
02, 03, 04, 05, 06 
and 07 – 
Incorporates 
Admin Letter 01 
Added additional window for Week 12 visit in order to 
proactively account for any subjects that may potentially 
be out of visit window due to concerns related to COVID-
19 pandemic. Allowing remote safety visits if needed due 
to COVID-19 concerns. 
Section 4.3 
Added additional guidance regarding remote visits in the 
event that in-office visits are not feasible due to COVID-
19 concerns. 
Footnote B and N modified to address potential extended 
Week 12 visit window and the dispensing/shipment of 
additional study drug 
Section 4.3.2  
Added additional window for Week 12 visit in order to 
proactively account for any subjects that may potentially 
be out of visit window due to concerns related to COVID-
19 pandemic. Allowing remote safety visits if needed due 
to COVID-19 concerns. 
Section 7.7.4 
Added language permitting local safety lab draws in cases 
where subjects may be may potentially be out of visit 
window due to concerns related to COVID-19 pandemic. 
Section 9.2.3:  
Revised to permit extended dosing period between Week 
8 and Week 12, if necessary, due to COVID-19 concerns, 
and to not permit entrance into the Extension Phase until a 
Randomization Phase Week 12 visit is conducted in the 
office. 
Section 9.4:  
Revised to permit overnight shipment of study drug, if 
necessary, due to COVID-19 concerns. 
General typographical errors have been corrected and 
administrative updates have been made throughout.  
16 Mar 2020 
19 Oct 2020 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 4 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Version 09 – 
Amendment 01, 
02, 03, 04, 05, 06 
07, and 08 – 
Incorporates 
Admin Letter 01 
Section 4.3 
Revised Schedule of Assessments to add an Additional 
Expanded Extension Phase, which provides eligible 
subjects with an additional 48 weeks of open-label 
treatment with troriluzole. 
15 Dec 2021 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 5  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Versi o n 1 0  –  
A me n d me nt 0 1, 
0 2, 0 3, 0 4, 0 5, 0 6 
0 7, 0 8 a n d 09  –  
I nc or p orates 
A d mi n Letter 0 1  
St u d y Desi g n a n d St u d y Sc he m atic  
Re vise d St u d y Desi g n secti o ns a n d St u d y Sc he m ati c t o 
a d d a n a d diti o nal 4 8 wee ks of o pe n -la b el tr eat me nt wit h 
tr oril uz ole t o t he A d diti o nal E x pa n de d E xte nsi o n P h ase . 
Secti o n 4. 3  
Re vise d Sc he d ul e of Assess me nts t o a d d a n a d diti o n al 4 8 
wee ks of o pe n -la bel treat me nt wit h tr oril uz ole t o t he 
A d diti o nal E x pa n de d E xte nsi o n P hase  ( Ta ble 7). 
Secti o ns 4. 3, 4. 3. 2, 7. 7. 4 a n d 1 0. 1. 4  
Re vise d t o reflect c ha n ge i n Me dic al M o nit or fr o m  
 
  
 t o 
 
 
Secti o n 1 7. 1 A p pe n di x I  
Re vise d t o reflect c ha n ge i n Me dic al M o nit or fr o m  
 
  
 t o 
  
 a n d a d diti o n of bac k-
u p Me dical M o nit or 
 
 
Ge ner al t y p o gr a p hical err ors ha ve b ee n c orr ecte d a n d 
a d mi nistr ati v e u p dat es ha ve bee n ma de t hr o u g h o ut.  
 
1 3 Oct 2 0 2 2  
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 6 of 97 
 
Draft Version 10; 13 Oct 2022 
 
BHV4157-202 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL 
OF ADJUNCTIVE TRORILUZOLE IN OBSESSIVE COMPULSIVE 
DISORDER  
CONFIDENTIALITY AND INVESTIGATOR STATEMENT 
The information contained in this protocol and all other information relevant to troriluzole are 
the confidential and proprietary information of Biohaven Pharmaceutical Holding Company 
Limited, and except as may be required by federal, state or local laws or regulation, may not be 
disclosed to others without prior written permission of Biohaven Pharmaceutical Holding 
Company Limited. 
I have read the protocol, including all appendices, and I agree that it contains all of the necessary 
information for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in accordance with the regulations stated in the Federal Code of Regulations for 
Good Clinical Practices and International Conference on Harmonization guidelines, and will 
make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Biohaven Pharmaceutical Holding 
Company Limited. or specified designees. I will discuss the material with them to ensure that 
they are fully informed about Biohaven and the study. 
 
 
Principal Investigator Name (printed) 
 
Signature 
 
Date 
 
 
 
 
 
Site Number 
 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
S T U D Y S U M M A R Y ( S Y N O P SI S)  
 
Title:  
A ra n d o mize d, d o u ble -bli n d, plac e b o -c o ntr olle d trial of a dj u ncti ve tr oril uz ole i n 
O bsessi ve C o m p ulsi ve Dis or der  
 
R ati o n ale:  
 
First -li ne tr eat me nt f or O bsessi ve C o m p ulsi ve Dis or der ( O C D ) i ncl udes 
c o g niti v e be ha vi or t hera p y a n d sele cti v e ser ot o ni n r e u pta ke i n hi bit ors ( S S RIs). 
N o net heless, u p t o 6 0 % of patie nts ha ve a n i n a de q uate res p o nse t o c o n v e nti o n al 
p har mac ot hera p y  1. W hile S S RIs a n d cl o mi pra mi ne ha ve bee n a p pr o ve d f or 
O C D, t he maj orit y of  patie nts d o n ot h a ve a n a d e q uate res p o nse t o 
p har mac ol o gic treat me nt, a n d s o me see k i n vasi ve n e ur os ur gical pr oc e d ures t o 
a meli orat e s y m pt o ms.  
T he pr o p ose d st u d y is base d o n re ce nt pre cli nical, cli nical, g e netic a n d 
ne ur oi ma gi n g st u dies t h at i m pli cat e gl u ta mat er gic h y peracti vit y i n t he 
pat h o ge nesis of O C D.  I n m ulti ple p u blis he d cli ni cal case st u dies, t h e use of 
a ge nts t hat m o d ul ate br ai n gl uta mate ha v e bee n s u g g este d t o ha v e effic ac y i n 
patie nts wit h refra ct or y O C D  2 -8 .  
Tr oril uz ole  is a n o v el gl uta mate m o d ulati n g dr u g t hat is bei n g de v el o pe d f or t he 
p ote nti al tr eat me nt of  O C D  as  a dj u ncti ve t hera p y t o sta n dar d of care treat me nts 
i n s u bjects w h o ha ve e x perie n ce d a n i na de q u ate r es p o nse  t o c urre nt 
p har mac ot hera p y .   
Tr oril uz ole  is a tri pe pti de pr o dr u g of t h e gl ut a mate m o d ulati n g a ge nt ril u z ole 
t hat has be e n o pti miz e d f or i m pr o ve d bi oa vaila bilit y, p har mac o ki netics a n d 
d osi n g. Ril uz ol e is c urre ntl y o nl y i n dic ate d f or A L S a n d has a n u m ber of n o n -
desira ble attri b utes t h at ha ve li mite d its cli nic al use. Ke y li mitati o ns of ril uz ole 
i ncl u de: 
•  • P o or or al bi o av ail a bilit y  — W he n ril uz ole is a d mi nistere d i n a ta blet f or m, 
a p pr o xi matel y 4 0 % is eit h er n ot a bs or be d or is m eta b olize d i n t he li ver 
bef ore reac hi n g s yste mi c cir c ulati o n.  
•  • Ne g ative f o o d effect  — Ril u z ole m ust be t a ke n o n a n e m pt y st o m ac h, at 
least o ne h o ur b ef ore or t w o h o urs after a me al. Fail ure t o a d her e t o t h ese 
g ui deli n es res ults i n l o wer dr u g le vels a n d p ote ntiall y decrease d t hera pe utic 
effects.  
•  • Ne g ative eff ect o n liv er  — Ril uz ole has be e n s h o w n t o ha ve d ose -
de pe n de nt li ver effects t h at i n cl u de ele v ati o ns o n li v er f u ncti o n te sts. Ta ki n g 
ril uz ol e nec essitates re g ular l a b orat or y m o nit ori n g of li ver f u ncti o n.  
•  • P h ar m ac oki neti c v ari a bilit y  — D ue t o e xte nsi ve first -pass meta b olis m a n d 
C Y P 1 A 2 meta b olis m.  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 8  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Tr oril uz ole  was de vel o pe d t o a d dr ess li mitati o ns of ril uz ol e t hat ha ve restrict e d 
its br oa der cli ni cal a p plic ati o n. B ase d o n t he pr ecli ni cal fe at ures of tr oril uz ol e 
a n d data fr o m a c o m plet e d  P hase 1 st u d y  of  tr oril uz ole, we a ntici p ate t he 
cli ni cal p h ar mac ol o g y t o offer f a v ora bl e pr o perties as c o m pare d t o a vaila ble 
ril uz ol e:  
•  Tr oril uz ole  is e x p ecte d t o ha ve b ett er or al bi o av ail a bilit y ; 
•  Tr oril uz ole  is e x p ecte d t o ha ve n o f o o d restricti o ns i m p ose d ; 
•  Tr oril uz ole  is desi g n e d t o release ril uz ol e aft er b y passi n g first-pass 
meta b olis m a n d t h us c o nfer l o w er over all dr u g b ur d e n t o t he liv er , w hic h 
ma y tra nsl ate i nt o a b etter saf et y a n d t oler a bilit y pr ofile;  
•  Tr oril uz ole  is e x p ecte d t o ha ve re d u ce d p h ar m ac oki netic v ari a bility a n d be 
d ose d o nly o nce d aily . 
As a n o pti miz e d  pr o dr u g of ril u z ole, th e re g ul at or y p at h wa y f or tr oril uz ol e will 
rel y o n t o xi c ol o g y data wit h tr oril u z ole i n r o d e nts a n d n o n-h u ma n pri m ates, 
cli ni cal e x perie n ce wit h tr oril u z ole i n ot her cli nical dis or ders s uc h as 
s pi n ocere bellar ata xi a, a n d t h e well-c hara cterize d saf et y e x perie nce of ril uz ole, 
w hic h has bee n m ar ke te d gl o ball y f or o ver 2 0 ye ars a n d is c o nsi dere d saf e a n d 
well t ol erat e d.  
T ar get 
P o p ul ati o n:  
Male a n d fe mal e o ut patie nt s u bj ects bet wee n t h e a ges of 1 8 - 6 5  years, 
i ncl usi ve, wit h a pri mar y  D S M -5 dia g n osis of O bsessi ve C o m p ulsi ve Dis or der 
(c o nfir me d b y t he MI NI) w h o ha ve ha d a n i n a de q uat e res p o nse t o Sta n dar d of 
Ca re me dicati o ns, i ncl u di n g t h eir c urre nt sta n dar d of care.  A n i na d e q uate 
res p o nse t o t heir c urre nt sta n d ar d of car e is defi n e d b y a Yale– Br o w n 
O bsessi ve C o m p ulsi ve Scal e ( Y -B O C S) sc ore of 1 9  or gr eater d es pite at le ast 
1 0 wee ks of treat me nt at Baseli ne 8 wit h t he m a xi m u m t oler ate d d ose of a n 
S S RI , cl o mi pra mi ne, ve nlafa xi ne or des ve nl afa xi n e . A d diti o nall y, O C D 
s y m pt o ms i n s u bjects ha d t o be pr ese nt f or ≥ 1  y ear a n d at le ast of m o der ate 
se verit y o n t h e Cli nical Gl o bal I m pressi o n Scale se v erit y of ill ness it e m.  
N u m ber of 
S u bjects:  
A p pr o xi matel y 2 2 6 ra n d o mize d s u bje cts  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
 
O bjecti ves:  
Pri m ar y O bjecti v es  
•  T he pri m ar y o bje cti ve of t he st u d y is t o e val u ate t he effica c y of Tr oril u z ole  
as a dj u ncti ve t h era p y i n s u bje cts wit h O C D  w h o ha ve ha d a n i n a de q uate 
res p o nse t o S S RI , cl o mi pra mi ne, v e nlafa xi ne or des v e nlafa xi ne tr eat m e nt  
Sec o n d ar y O bjecti ves  
•  T o assess t he safet y a n d t olera bilit y of tr oril uz ol e, rel ati ve t o pla ce b o, i n 
s u bjects wit h O C D 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n f u ncti o n al 
disa bilit y  as me as ure d b y t he S he e ha n Disa bilit y Scale ( S D S ) 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n gl o bal 
f u ncti o ni n g as meas ure d b y t he Cli nical Gl o bal I m pr essi o n - Se verit y Scale  
( C GI-S ) 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n o bsessi ve 
s y m pt o mat ol o g y as me as ure d b y t he c ha n ge i n t he Y ale Br o w n O bsessi ve  
C o m p ulsi ve Scale ( Y -B O C S ) o bsessi o ns s u bscale  
E x pl or at or y O bjecti ves  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n de pressi ve 
s y m pt o mat ol o g y as me as ure d b y t he Q ui c k I n ve nt or y of De pressi ve 
S y m pt o mat ol o g y - Self Re p ort ( QI D S -S R ) 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n a n xiet y 
s y m pt o ms as meas ure d b y t he Be c k A n xiet y I n ve nt or y  (B AI ) 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n i nsi g ht 
re gar di n g o bsessi o nal b eli efs as meas ure d b y t h e Br o w n Assess me nt of 
Beliefs Scale ( B A B S ) 
•  T o assess p har mac o d y na mic eff ects of tr oril uz ole vs. place b o o n mar kers of 
s y na ptic pl asticit y as m eas ure d b y plas m a le v els of B D N F a n d pr o B D N F  
•  T o c hara cteri ze t h e p har m ac o ki n eti cs of tr oril u z ole b ase d o n s parse 
sa m pli n g 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 10 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Study 
Design: 
BHV4157-202 is a Phase IIb/III, multicenter, randomized, double-blind, 
placebo-controlled, 2- arm study designed to assess safety, tolerability, and 
efficacy of troriluzole as adjunctive therapy when added to standard of care 
treatment in subjects with Obsessive Compulsive Disorder who failed to 
respond adequately to prior pharmacotherapy. Current treatment failure is 
defined by a Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score of 19 
or greater despite at least 8 weeks of treatment at screening and at least 10 
weeks of treatment at baseline with an adequate dose of an SSRI, clomipramine, 
venlafaxine or desvenlafaxine. 
Subjects who are stable on Standard of Care (SOC) medication and having an 
inadequate response (as defined above) will be randomized to additionally 
receive placebo (QD) or troriluzole (200 mg QD, after four weeks at 140 mg 
QD). 
Dosing will continue for approximately 12 weeks. Eligible subjects will have 
the opportunity to continue in a 48 week open-label extension phase. Those 
subjects not continuing in the 48 week extension will return to the clinic two 
weeks after discontinuing study medication for a follow-up safety visit.  
For subjects entering the Extension Phase, their first in-person extension visit 
will be four weeks after the Week 12 Randomization Phase visit. Subjects will 
undergo visits every fourth week through Week 12 of this phase. Then subjects 
will undergo visits every 12 weeks up to Week 48 of this phase. Subjects who 
complete the 48 week extension may have the opportunity to receive an 
additional 48 weeks of open-label treatment with troriluzole in an Expanded 
Extension Phase depending on when they completed the first 48 weeks. Those 
subjects not continuing in the 48 week Expanded Extension Phase will return to 
the clinic two weeks after discontinuing study medication for a follow-up safety 
visit. 
For subjects completing the initial 48 week Extension Phase and continuing 
directly into the Expanded Extension Phase with no dose interruption, their first 
in-person expanded extension visit will be 12 weeks after the extension week 48 
visit. Subjects will undergo visits every 12 weeks up to Week 96 of this phase. 
Subjects who complete the 48 week Expanded Extension Phase may have the 
opportunity to receive an additional 96 weeks of open-label treatment with 
troriluzole in the Additional Expanded Extension Phase, for a total of 192 
weeks of open-label treatment, depending on when they completed the first 96 
weeks. Those subjects not continuing in the Additional Expanded Extension 
Phase will return to the clinic two weeks after discontinuing study medication 
for a follow-up safety visit. 
Subjects who previously completed the initial 48 week Extension Phase and 
have exited the study will have the opportunity to return and receive an 
additional 48 weeks of open-label treatment with troriluzole provided it has not 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 1 1  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
bee n m ore t ha n 3 m o nt hs si nce t he y c o m pl ete d t he st u d y  a n d t he PI belie ves it 
offers a n acce pta bl e ris k -be nefit pr ofile . All s u bj ects will u n der g o a p ost st u d y 
dr u g ter mi n ati o n visit t w o wee ks after t he last d ose of st u d y dr u g.  
S u bjects w h o c o m pl ete d t he E x p a n de d  E xt e nsi o n P hase a n d ha ve e xite d t he 
st u d y will ha ve t he o p p ort u nit y t o r et ur n a n d re cei v e a n a d diti o nal 4 8  we e ks of 
o pe n -la bel tre at me nt wit h tr oril uz ole i n a n A d diti o n al E x pa n de d E xte nsi o n 
P hase pr o vi de d it h as n ot bee n m ore t ha n 4  we e ks  si nce t he y c o m pl ete d t he 
st u d y a n d t he PI belie ves it offers a n ac ce pt a ble ris k-be nefit pr ofile. S u bj ects 
w h o c o m plet e t he i nitial 4 8  wee ks of t h e A d diti o n al E x pa n de d E xte nsi o n P hase 
will ha ve t he o p p ort u nit y t o c o nti n u e a n d rec ei ve a n a d diti o n al 4 8 wee ks of 
o pe n -la bel tre at me nt pr o vi de d t he PI belie ves it offers a n acce pta ble ris k-be nefit 
pr ofile. All s u bj ects will u n der g o a p ost st u d y  dr u g t er mi nati o n visit t w o wee ks 
after t h e last d ose of st u d y dr u g.  
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 12 of 97 
 
Draft Version 10; 13 Oct 2022 
 
 
STUDY SCHEMATIC* 
   
 
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 13 of 97 
 
Draft Version 10; 13 Oct 2022 
 
TABLE OF CONTENTS 
 
SUMMARY OF CHANGES .........................................................................................................2 
BHV4157-202..................................................................................................................................6 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF 
ADJUNCTIVE TRORILUZOLE IN OBSESSIVE COMPULSIVE DISORDER ..........6 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT ...............................................6 
STUDY SUMMARY (SYNOPSIS) ..............................................................................................7 
STUDY SCHEMATIC* ..............................................................................................................12 
TABLE OF CONTENTS ............................................................................................................13 
LIST OF TABLES .......................................................................................................................16 
LIST OF FIGURES .....................................................................................................................16 
LIST OF ABBREVIATIONS .....................................................................................................17 
1 
INTRODUCTION AND RATIONALE .............................................................................19 
1.1 
Background ......................................................................................................................19 
1.1.1 
Obsessive Compulsive Disorder (OCD) ...................................................................19 
1.1.2 
Rationale for Troriluzole in the Treatment of OCD...............................................19 
1.1.3 
Troriluzole ..................................................................................................................20 
1.1.3.1 
Pre-Clinical Studies .............................................................................................20 
1.1.3.2 
Clinical Experience ..............................................................................................21 
1.1.4 
Potential for Drug-Drug Interactions ......................................................................23 
1.1.5 
Clinical Adverse Event Profile ..................................................................................24 
1.1.5.1 
Troriluzole ............................................................................................................24 
1.1.5.2 
Riluzole..................................................................................................................24 
1.1.6 
Potential Risk to Fetal Development ........................................................................27 
1.2 
Study Rationale ................................................................................................................27 
1.2.1 
Study Design Rationale..............................................................................................27 
1.2.2 
Pharmacokinetics and Dose Selection Rationale ....................................................29 
1.3 
Research Hypothesis ........................................................................................................29 
2 
STUDY OBJECTIVES ........................................................................................................30 
2.1 
Primary .............................................................................................................................30 
2.2 
Secondary..........................................................................................................................30 
2.3 
Exploratory .......................................................................................................................30 
3 
STUDY ENDPOINTS ..........................................................................................................31 
3.1 
Primary .............................................................................................................................31 
3.2 
Secondary..........................................................................................................................31 
3.3 
Exploratory .......................................................................................................................31 
4 
STUDY PLAN .......................................................................................................................32 
4.1 
Study Design and Duration .............................................................................................32 
4.2 
Study Schematic ...............................................................................................................34 
4.3 
Schedule of Assessments ..................................................................................................35 
4.3.1 
Screening Phase ..........................................................................................................49 
4.3.2 
Randomization Phase ................................................................................................49 
4.3.3 
Extension Phase ..........................................................................................................51 
4.3.4 
Expanded Extension Phase (if applicable) ...............................................................51 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 14 of 97 
 
Draft Version 10; 13 Oct 2022 
 
4.3.5 
Additional Expanded Extension Phase (if applicable) ...........................................52 
4.4 
Post Study Access to Therapy (if applicable) ................................................................52 
5 
POPULATION ......................................................................................................................52 
5.1 
Number of Subjects..........................................................................................................52 
5.2 
Inclusion Criteria .............................................................................................................52 
5.2.1 
Informed Consent ......................................................................................................52 
5.2.2 
Age and Sex ................................................................................................................52 
5.2.3 
Target Population ......................................................................................................53 
5.3 
Exclusion Criteria ............................................................................................................55 
5.3.1 
Target Disease Exceptions .........................................................................................55 
5.3.2 
Medical History Exclusions .......................................................................................56 
5.3.3 
Physical and Laboratory Test Findings ...................................................................58 
5.3.4 
Prohibited Treatments and/or Therapies ................................................................59 
5.4 
Prohibited Concomitant Medication ..............................................................................60 
5.5 
Woman of Childbearing Potential ..................................................................................62 
5.6 
Deviation from Inclusion/Exclusion Criteria ................................................................64 
6 
STUDY CONDUCT AND DESCRIPTION OF STUDY PROCEDURES .....................64 
6.1 
Study Materials ................................................................................................................64 
7 
ELIGIBILITY ASSESSMENTS .........................................................................................65 
7.1 
Massachusetts General Hospital-Treatment Response Questionnaire for 
OCD (MGH-TRQ-OCD) .................................................................................................65 
7.2 
Mini Mental State Examination (MMSE) .....................................................................65 
7.3 
MINI International Neuropsychiatric Interview (MINI) .............................................65 
7.4 
Borderline Personality Disorder Module (BPD) ...........................................................65 
7.5 
SAFER Interview .............................................................................................................65 
7.6 
Medical History ................................................................................................................65 
7.7 
Safety Assessments ...........................................................................................................66 
7.7.1 
Vital Signs and Physical Measurements (Height and Weight) ..............................66 
7.7.2 
Electrocardiogram (ECG) .........................................................................................66 
7.7.3 
Physical Exam ............................................................................................................66 
7.7.4 
Laboratory Assessments ............................................................................................66 
7.7.4.1 
BDNF and proBDNF Blood Sample Collection ................................................67 
7.7.4.2 
Pharmacokinetics .................................................................................................68 
7.7.4.3 
Pharmacogenetics ................................................................................................68 
7.7.4.4 
Pregnancy Testing ................................................................................................68 
7.7.4.5 
Evaluation of Laboratory Assessments ..............................................................69 
7.7.5 
Sheehan Suicidality Tracking Scale (Sheehan STS) ...............................................70 
7.8 
Clinical Outcome Assessments........................................................................................70 
7.8.1 
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) .............................................70 
7.8.2 
Sheehan Disability Scale (SDS) .................................................................................71 
7.8.3 
Clinical Global Impression – Severity Scale (CGI-S) .............................................71 
7.8.4 
Brown Assessment of Beliefs Scale (BABS) .............................................................71 
7.8.5 
Quick Inventory of Depressive Symptomatolgy – Self Report (QIDS-SR) ..........72 
7.8.6 
Beck Anxiety Inventory (BAI) ..................................................................................72 
8 
EARLY DISCONTNUATION OF STUDY .......................................................................72 
9 
STUDY DRUG MANAGEMENT .......................................................................................72 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 15 of 97 
 
Draft Version 10; 13 Oct 2022 
 
9.1 
Description of Study Drug...............................................................................................72 
9.1.1 
Investigational Product .............................................................................................72 
9.1.2 
Packaging, Shipment and Storage ............................................................................73 
9.2 
Dose and Administration .................................................................................................73 
9.2.1 
Randomization Phase ................................................................................................73 
9.2.2 
Extension Phase ..........................................................................................................73 
9.2.3 
Method of Assigning Patient Identification .............................................................74 
9.2.4 
Selection and Timing of Dose and Administration .................................................75 
9.2.5 
Dose Modifications .....................................................................................................75 
9.3 
Blinding and Unblinding .................................................................................................76 
9.4 
Treatment Compliance ....................................................................................................76 
9.5 
Destruction and Return of Study Drug ..........................................................................77 
10 ADVERSE EVENTS ............................................................................................................77 
10.1 
Serious Adverse Events ...................................................................................................77 
10.1.1 
Definition of Serious Adverse Event (SAE) .............................................................77 
10.1.2 
Definition of Terms ....................................................................................................78 
10.1.3 
Classification of Adverse Events...............................................................................79 
10.1.4 
Collection and Reporting Serious Adverse Events .................................................79 
10.1.5 
Overdose .....................................................................................................................80 
10.1.6 
Pregnancy ...................................................................................................................80 
10.1.7 
Potential Drug Induced Liver Injury (DILI)...........................................................81 
10.2 
Non-serious Adverse Events............................................................................................81 
10.2.1 
Collection and Reporting of Non-Serious Adverse Events ....................................81 
11 STATISTICS .........................................................................................................................82 
11.1 
General Procedures .........................................................................................................82 
11.2 
Sample Size .......................................................................................................................82 
11.3 
Populations for Analysis ..................................................................................................83 
11.4 
Statistical Methods ...........................................................................................................83 
11.4.1 
Demographic and Baseline Characteristics .............................................................83 
11.4.2 
Primary Endpoint(s) ..................................................................................................83 
11.4.3 
Secondary Endpoint(s) ..............................................................................................84 
11.4.4 
Adjustment for Multiplicity ......................................................................................84 
11.4.5 
Missing Data ...............................................................................................................84 
11.4.6 
Analysis of Safety .......................................................................................................84 
11.5 
Schedule of Analyses ........................................................................................................85 
12 ETHICS AND RESPONSIBILITIES .................................................................................85 
12.1 
Data and Safety Monitoring Committee ........................................................................86 
12.2 
Institutional Review Board/Independent Ethics Committee .......................................86 
12.3 
Informed Consent ............................................................................................................86 
12.4 
Case Report Forms ..........................................................................................................87 
12.5 
Records Management and Retention .............................................................................88 
12.6 
Source Documentation.....................................................................................................89 
12.7 
Study Files and Record Retention ..................................................................................89 
13 AMENDMENTS ...................................................................................................................89 
14 STUDY REPORT AND PUBLICATIONS ........................................................................89 
15 STUDY DISCONTINUATION ...........................................................................................90 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 16 of 97 
 
Draft Version 10; 13 Oct 2022 
 
16 CONFIDENTIALITY ..........................................................................................................90 
17 APPENDICES .......................................................................................................................91 
17.1 
APPENDIX I - Names of Study Personnel ....................................................................91 
17.2 
APPENDIX II - Potent and Moderate Inhibitors and Inducers of the 
CYP1A2 Enzyme System* ..............................................................................................92 
18 REFERENCES CITED ........................................................................................................93 
CLINICAL PROTOCOL APPROVAL FORM .......................................................................97 
 
LIST OF TABLES 
 
Table 1: 
Schedule of Assessments and Events - Randomization Phase .........................36 
Table 2: 
Schedule of Assessments and Events - Extension Phase...................................40 
Table 3: 
Schedule of Assessments and Events – Expanded Extension Phase 
(continuing subjects) ............................................................................................42 
Table 4: 
Schedule of Assessments and Events – Expanded Extension Phase (returning 
subjects) ................................................................................................................43 
Table 5: 
Schedule of Assessments and Events – Additional Expanded Extension Phase 
(continuing subjects) ............................................................................................45 
Table 6: 
Schedule of Assessments and Events – Additional Expanded Extension Phase 
(returning subjects) ..............................................................................................46 
Table 7: 
Schedule of Assessments and Events – Additional Expanded Extension Phase 
(all continuing subjects) .......................................................................................48 
 
LIST OF FIGURES 
Figure 1:  
Study Schematic ...................................................................................................34 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 17 of 97 
 
Draft Version 10; 13 Oct 2022 
 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
Bid 
Twice Daily 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
Cmax 
Maximum Plasma Concentration 
CNO 
Certificate of Non-Objection 
CONMED 
Concomitant Medication 
COVID-19 
Coronavirus disease 2019 
CRF 
Case Report Form 
DSMC 
Data and Safety Monitoring Committee 
ECG 
Electrocardiogram 
GCP 
Good Clinical Practice 
HR 
Heart Rate 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
iv 
Intravenous 
kg 
Kilogram 
L 
Liters 
mg 
Milligram 
min 
Minute 
mmHg 
Millimeters Mercury 
NOEL 
No Observed Effect Level 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 18 of 97 
 
Draft Version 10; 13 Oct 2022 
 
NOAEL 
No Observed Adverse Event Level 
PK 
Pharmacokinetic 
po 
By Mouth, Orally 
qd 
Once Daily 
SAE 
Serious Adverse Event 
SOC 
Standard of Care 
SSRI 
Selective Serotonin Reuptake Inhibitor 
ULN 
Upper Limit of Normal 
USPI 
US Package Insert 
WHO 
World Health Organization 
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 19 of 97 
 
Draft Version 10; 13 Oct 2022 
 
1 INTRODUCTION AND RATIONALE 
1.1 
Background 
Biohaven Pharmaceutical Holding Company Limited [Biohaven] is developing a new drug, 
troriluzole, for the treatment of OCD as well as for other neurologic and psychiatric disorders.  
Troriluzole is a novel and optimized prodrug of the glutamatergic agent riluzole. The FDA 
originally approved riluzole (RILUTEK®) 50 mg twice-a-day (NDA #20-599) for the treatment 
of patients with Amyotrophic Lateral Sclerosis (ALS). Riluzole is only indicated for ALS and 
has a number of non-desirable attributes that have limited its clinical use.  Troriluzole is a 
tripeptide prodrug of the glutamate modulating agent riluzole that has been optimized for 
improved bioavailability, pharmacokinetics and dosing. The proposed study in OCD is based on 
recent preclinical, clinical and neuroimaging studies that implicate glutamatergic hyperactivity in 
the pathogenesis of OCD 6-10. Biohaven hypothesizes that the pleiotropic effects of riluzole (e.g., 
glutamate modulation) may target mechanisms underlying pathologic brain function that is 
associated with OCD, and thus provide symptomatic benefit in patients suffering from OCD. 
1.1.1 
Obsessive Compulsive Disorder (OCD) 
Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disease, affecting 2-3% of the 
general population 11. According to the National Comorbidity Survey, approximately half of 
OCD cases are characterized as severe 1. Patients with OCD suffer from intrusive, obsessional 
thoughts that are typically ego-dystonic and commonly engage in time-consuming compulsive 
behaviors in in an attempt to attenuate their anxiety. The anxiety associated with OCD symptoms 
can be intense and persist chronically over time. Existing therapies, including pharmacotherapy 
and well-established cognitive-behavioral techniques, can significantly reduce symptoms in 
many patients. However, persistent residual symptoms are the norm and can lead to markedly 
restricted lives even in treated patients; and a substantial number of patients are treatment 
refractory 12. Indeed, treatment refractory OCD is a sufficiently debilitating condition that it is 
the only psychiatric disease for which psychosurgery still remains an established therapy of last 
resort 13,14. Augmentation strategies with neuroleptic medications can improve the effectiveness 
of selective serotonin inhibitors (SRIs) therapy but do not eliminate OCD symptoms 15,16.  
Additionally, neuroleptic medications are associated with adverse effects including tardive 
dyskinesia, extrapyramidal symptoms and metabolic syndrome. The clinical observation that few 
patients experience a complete response to SRIs or dopamine antagonists suggests that other 
neurochemical systems are involved in the pathophysiology of OCD. Novel pharmacological 
treatments are needed to improve treatment outcomes. 
1.1.2 
Rationale for Troriluzole in the Treatment of OCD 
The proposed study is based on recent preclinical, clinical, genetic and neuroimaging studies that 
implicate glutamatergic hyperactivity in the pathogenesis of OCD 4,5,9,10,17-25. The Glutamate 
transporter gene SLC1A1 has been associated with the transmission of OCD in some studies, 
providing some genetic evidence of the association between altered glutamate neurotransmission 
and OCD 24. Further genome-wide association studies have identified the glutamate related 
SAPAP/DLGAP proteins as additional genes of interest 26,27. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Ne ur oi ma gi n g st u dies ha ve als o c o nsiste ntl y i de ntifi e d i ncre ase d bl o o d fl o w, meta b olis m a n d 
brai n acti vit y i n t h e or bit ofr o ntal c orte x ( O F C), striat u m, a n d t hala m us of i n di vi d uals wit h O C D 
2 8. T he striat u m is t h e pri m ar y i n p ut n u cle us of t he b asal ga n glia, a n et w or k of s u bc ortic al 
str uct ures; t h e O F C is t h e maj or tar g et of c ortical i n p ut t o t he b asal ga n glia a n d t he t hala m us is a 
maj or o ut p ut; it pr oje cts bac k t o t he c orte x, f or mi n g  a fee d ba c k l o o p.  T hese str u ct ures, w hic h 
are h y peracti ve i n O C D, t h us c o nstit ut e part of t he c ortic o -stri at o-t h ala m o-c orti cal ( C S T C) 
circ uitr y.  I nf or mati o n fl o ws t hr o u g h t his circ uitr y i n t w o parall el l o o ps: t he dir ect pat h wa y, 
w hic h pr o vi de s net p ositi ve f ee d bac k t o t he c orte x, a n d t he i n dir ect p at h wa y, w hic h pr o vi d es net 
ne gati v e fee d ba c k.  Acti vit y i n t hese par all el circ uitri es e xists i n a ti g htl y r e g ulate d d y na mic 
bala nc e.  A lea di n g e x pla n at or y m o d el f or O C D s u g gests t hat o ver acti vit y i n t he direct p at h wa y 
relati ve t o t he i n direct p at h wa y res ults i n a disi n hi bit e d t hal a m us a n d t h e creati o n of a self-
per pet uati n g circ uit bet wee n t he t h ala m us a n d t he or bit ofr o ntal c ort e x t hat dri ves O C D 
s y m pt o ms 2 9 ,3 0. Cli ni cal st u dies s u p p ort t his m o d el. C o m pare d t o c o ntr ols, tr eat me nt naï ve O C D 
patie nts ha ve si g nifica ntl y i n crease d gl uta m ater gic a cti vit y as me as ure d b y pr ot o n m a g neti c 
res o na nce s pectr osc o p y ( 1 H-M R S) 
3 1 ,3 2.  M ore o ver, treat m e nt wit h a n S RI was ass ociate d wit h a 
si g nifica nt decli ne i n ca u date gl uta m ate c o nce ntrati o n i n t h ose i n di vi d uals w h o res p o n de d t o S RI 
treat me nt  3 1 -3 4. T h ese cli nical fi n di n gs ar e c o nsiste nt wit h p har ma c ol o gi cal st u dies 
de m o nstrati n g a n S RI -i n d uc e d i n hi biti o n of gl uta mat e rele ase 3 5.  
O pe n la bel d ata a n d s mall cli nical st u dies als o s u g gest be nefit fr o m t he gl uta mate m o d ulat or 
ril uz ol e i n i n di vi d uals wit h O C D 8 ,3 6 ,3 7. I n a st u d y b y E ma m za de hf ar d  4, pati e nts tre ate d wit h 
ril uz ol e a u g m e ntati o n of t he S S RI fl u v o x a mi ne s h o we d si g nifica ntl y gre ater re d u cti o ns i n t heir 
Y -B O C S sc ore a n d m ore pati e nts ac hi e ve d re missi o n c o m pare d t o pla ce b o o ver t h e 1 0 wee k 
c o urse of t he trial. Ril uz ole has se veral m o des of a cti o n; pr o mi ne nt a m o n g t he m, are a n 
i n hi biti o n of pres y na ptic gl uta m ate release a n d i ncr e ase d gl uta mat e c ycli n g d ue t o effects o n t he 
e xcit at or y a mi n o aci d tra ns p ort ers ( E A A Ts) l ocat e d o n glia 3 8. 
1. 1. 3  
Tr oril u z ol e  
1. 1. 3. 1  
Pr e -Cli ni c al St u di e s  
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 1  of 9 7  
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1. 1. 3. 2  
Cli ni c al E x p eri e n c e  
C CI
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 2  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1. 1. 3. 2. 1  
T r oril u z ol e P h a s e  I - St u d y B H V 4 1 5 7 -1 0 1  
1. 1. 3. 2. 2  
B H V 4 1 5 7 P h a s e 2 –  B H V 4 1 5 7 -2 0 1  
B H V 4 1 5 7 -2 0 1 was a P hase 2 b/ 3, m ultic e nter, ra n d o mize d, d o u ble -bli n d, pla ce b o -c o ntr olle d 
parall el -gr o u p st u d y desi g n e d t o assess t he safet y, t ol era bilit y, a n d effica c y of tr oril uz ol e i n 
s u bjects wit h s pi n oc ere bellar ata xi a ( S C A). S u bjects were ra n d o mi ze d t o  re cei v e tr oril uz ol e ( 1 4 0 
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 3  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
m g P O o nce dail y [ Q D]) or plac e b o f or 8 wee ks. A t otal of 1 4 1 s u bje cts were ra n d o mize d i nt o 
t he d o u ble-bli n d ra n d o miz ati o n p hase ( 7 1 s u bj ects i n t he tr oril uz ol e 1 4 0 m g Q D gr o u p a n d 
7 0  s u bjects i n t h e pla ce b o gr o u p).  
D uri n g t he d o u ble -bli n d ra n d o mizati o n p hase, a d mi nistrati o n of tr oril u z ole at 1 4 0 m g Q D f or 
8  wee ks was well t oler ate d i n a d ult s u bj ects wit h S C A. T here were n o deat hs re p orte d d uri n g t he 
ra n d o miz ati o n p h ase of t his st u d y. Tre at m e nt-e mer g e nt S A Es were re p orte d f or 5 ( 3 . 5 5 %) 
s u bjects, i ncl u di n g 4 tr oril uz ole -tre ate d s u bj ects (ast he nia, atrial fi brillati o n, bl o o d cr eati ne 
p h os p h o ki nase i ncre ase d, de h y drati o n, bac k p ai n a n d cere bral i nfarcti o n), a n d 1  plac e b o -tre ate d 
s u bject (c h est disc o mf ort). N o cli ni call y me a ni n gf ul tr e n ds i n la b or at or y val ues were i de ntifi e d 
i n t his st u d y. N o s u bject h a d A S T or A L T la b or at or y a b n or maliti es > 3 X U L N. 
S u bjects c o m pleti n g t he d o u ble -bli n d ra n d o mizati o n p hase were offere d 4 8 wee ks of o pe n -la bel 
treat me nt wit h tr oril uz ol e ( 1 4 0 m g P O Q D) i n a n e xt e nsi o n p hase. O ne h u n dre d a n d t hirt y (1 3 1 ) 
s u bjects c o nti n ue d i nt o t he o p e n-la bel e xt e nsi o n p hase, w hic h was o n g oi n g as of Oct o ber 2 0 1 7.  
At t hat ti me, t he preli mi nar y safet y pr ofile of tr oril u z ole 1 4 0 m g Q D was c o nsiste nt wit h t he 
tr oril uz ole safety pr ofile o bser v e d d uri n g t h e ra n d o mizati o n p hase.  
1. 1. 4  
P ot e nti al f or Dr u g -Dr u g I nt er a cti o n s  
Cli nic al dr u g i ntera cti o n st u dies f or tr oril u z ole h a ve n ot bee n c o n d u cte d y et.  
T r oril uz ole: tr oril u z ole, itself, is n ot e x pecte d t o i nterfere wit h dr u g m eta b olis m a n d its cle a va ge 
via plas m a pe pti dases re n der s it u nli kel y t o be affect e d si g nific a ntl y b y li ver c yt oc hr o m e P 4 5 0 
i n hi bit ors. T r oril uz ole has t h e f oll o wi n g k n o w n p har mac o ki n eti c/ m eta b olis m para met ers:  
•  N ot a n i n hi bit or of C Y P 3 A 4, C Y P 1 A 2, or  C Y P 2 D 6  
•  I n C Y P i n d ucti o n st u di es: 
 
○ T he esti mat e d E C 5 0 a n d E ma x f or C Y P 1 A 2 m R N A was 1. 4 4 μ M a n d 3. 4 7 -f ol d 
i n d ucti o n, res pe cti v el y; 
○ T he esti mat e d E C 5 0 a n d E ma x f or C Y P 2 B 6 m R N A was 1 2. 6 μ M a n d 2 7. 0 -f ol d 
i n d ucti o n, r es pecti vel y; a n d  
○ T r oril uz ole di d n ot i ncr ease C Y P 3 A 4 m R N A at d oses u p t o 3 0  μ M  
Ril uz ol e Meta b olis m: tr oril u z ole meta b oliz es t o ril u z ole. As per t he U S PI, ril uz ol e meta b olis m 
has bee n assesse d i n s pecial p o p ulati o ns, c har act eriz e d b y he patic i m pair me nt ( 2 t o 3 f ol d 
i ncrease i n A U C wit h C hil d-P u g h Sc ores of A a n d B), re nal i m pair me nt ( n o eff ect), a ge ( n o 
effect), g e n der ( n o effe ct), s m o kers ( 2 0 % fast er eli mi nati o n) a n d r ace (Ja pa n ese c o m p are d t o 
Ca ucasia ns: n o effect).  
Effect of ot her dr u gs o n Ril u z ole m eta b olis m: I n vitr o st u dies usi n g h u ma n li ver micr os o mal  
pre parati o ns s u g gest t hat C Y P 1 A 2 is t he pri n ci pal is oz y me i n v ol ve d i n t he i niti al o xi d ati v e 
meta b olis m of ril uz ol e a n d, t h eref ore, p ot e nti al i nter acti o ns m a y occ ur w he n ril uz ol e is gi ve n 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 4  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
c o nc urre ntl y wit h a g e nts t hat affect C Y P 1 A 2 acti vit y. P ote ntial i n hi bit ors of C Y P 1 A 2 (e. g., 
ci pr ofl o x a ci n, e n o x a ci n, fl u v o x a mi n e, m et h o xs al e n, m e xil eti n e, or al c o ntr a c e pti v es, 
t hi a b e n d a z ol e, v e m ur af e ni b, zil e ut o n) c o ul d decr ease t he rat e of ril u z ole eli mi nati o n, w hile 
i n d ucers of C Y P 1 A 2 (e. g., ci garette s m o ke, c harc o al-br o ile d f o o d, rif a m pi ci n, a n d o m e praz ole) 
c o ul d i ncr ease t h e rate of ril uz ole eli mi nati o n.  
Effect of Ril uz ole o n t he Meta b olis m of Ot her Dr u gs: C Y P 1 A 2 is t he pri nci pal is oe nz y me 
i n v ol ve d i n t he i niti al o xi d ati v e meta b olis m of ril uz ole; p ot e nti al i ntera cti o ns ma y o cc ur w he n 
ril uz ol e is gi ve n c o nc urre ntl y wit h ot h er a ge nts w hic h are als o m eta b olize d pri maril y b y 
C Y P 1 A 2 (e. g., t he o p h ylli ne, caffei ne, a n d t acri n e). C urre ntl y, it is n ot k n o w n w het her ril uz ole 
has a n y p ote ntial f or e nz y me i n d ucti o n i n h u m a ns.  
1. 1. 5  
Cli ni c al A d v er s e E v e nt Pr ofil e  
1. 1. 5. 1  
Tr oril u z ol e  
1. 1. 5. 2  
Ril u z ol e  
Cli nic al i nf or mati o n o n ril u z ole, as reflecte d i n t he U S PI, is pre d o mi na ntl y b ase d o n e x perie nce 
fr o m a p pr o xi m atel y 4 0 0 0 patie nts gi ven ril uz ole f or A L S. Refer t o t he U S Prescri bi n g 
I nf or mati o n ( 1 5) w here gr eat er det ails o n t h e a d verse e ve nt pr ofile of ril uz ole ca n be f o u n d.  T he 
f oll o wi n g s u m marizes rele va nt i nf or mati o n. 
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 5  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
O verall, ril uz ol e ta blets ha ve b ee n well t ol erat e d i n p o p ulati o ns wit h A L S a n d di verse 
ne ur o ps yc hiatric c o n diti o ns t h at i ncl u de Maj or De pr essi ve Dis or der ( M D D ), Ge nerali ze d 
A n xiet y Dis or der ( G A D ) a n d s pi n ocer e bellar ata xi a . I n ra n d o miz e d c o ntr olle d trials c o m pari n g a 
1 0 0 m g dail y d ose of ril uz ole wit h place b o, n o A Es occ urre d at rates gre ater t ha n 5 % a n d t wice 
t hat of pl ace b o. T he A Es occ urri n g gr eat er t ha n 5 % a n d at l east 2 % m or e t ha n pl ace b o i ncl u d e d 
ast he nia ( 1 8 % vs 1 2 % pl ace b o) a n d n a usea ( 1 4 % vs 9 %).  T hese t w o A Es s h o we d tre n ds f or a 
d ose res p o nse ( 1 6). T he p u blis he d  lit erat ure o n t he use of ril uz ol e ta blets i n ps yc hiatri c dis or ders, 
w hile ge ner all y c o m pri se d of c ase -series, is c o nsist e nt wit h t his t olera bilit y pr ofil e.  
T he m ost c o m m o nl y o bser v e d A Es ass ociate d wit h t he use of ril uz ole t a blets m ore fre q ue ntl y 
t ha n place b o tr eate d p ati e nts were:  
•  ast he nia;  
•  na usea;  
•  dizzi n ess;  
•  d ecrease d l u n g  f u n cti o n;  
•  diarr hea;  
•  a b d o mi nal pai n;  
•  p ne u m o nia;  
•  v o miti n g;  
•  verti g o;  
•  circ u m or al parest hesi a;  
•  a n ore xia; a n d  
•  s o m n ole nce. 
A p pr o xi matel y 1 4 % ( n = 1 4 1) of t he 9 8 2 i n di vi d u als wit h A L S w h o recei ve d ril uz ole i n pre -
mar keti n g cli nic al trials disc o nti n ue d tr eat me nt b eca use of a n a d verse e x perie nc e. Of t h ose 
patie nts w h o disc o nti n ue d d u e t o a d v erse e ve nts, t h e m ost c o m m o nl y re p ort e d  were: na use a, 
a b d o mi nal pai n, c o nsti pati o n, a n d A L T ele v ati o ns. I n a d ose res p o nse st u d y i n A L S pati e nts, t he 
rates of disc o nti n uati o n of RI L U T E K f or ast he nia, n a usea, a b d o mi nal p ai n, a n d A L T ele v ati o n 
were d ose relate d. T he A Es of ast h e nia, n a usea, dizzi ness, di arr hea, a n ore xi a, verti g o, 
s o m n ole nce, a n d circ u m oral parest h esia were d ose r elate d. Assess me nt of p ul m o nar y A Es is 
c o nf o u n de d b y t he u n d erl yi n g ill n ess, A L S, w hic h is ass ociate d wit h res pirat or y  s y m pt o ms. 
 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 6  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1. 1. 5. 2. 1  
El e v ati o n s i n Li v er F u n cti o n T e st s  
T r oril uz ole has n ot b ee n ass ociate d wit h si g nific a nt c ha n ges i n li v er f u ncti o n or pat h ol o g y i n 
n o ncli ni cal t o xic ol o g y st u dies t o d ate, as reflecte d i n t he I B.  N o cli nicall y si g nifica nt L F T 
c ha n ges were o bser ve d o n st u d y dr u g i n B H V 4 1 5 7 -1 0 1.  I n t he o n g oi n g cli n i cal trial i n S C A, 
L F Ts re mai n bli n de d; h o we ver, n o s u bjects were re q uire d t o disc o nti n ue st u d y me di cati o n d ue t o 
ele vate d L F Ts.   
Ril uz ol e  is ass ociate d wit h ele vati o ns i n a mi n otr a nsferases t hat h a ve bee n r efle cte d i n m o nit ori n g 
preca uti o ns t hat will be f oll o we d wit hi n t his pr ot oc ol. E x perie n ce i n al m ost 8 0 0 A L S patie nts 
i n dicates t hat a b o ut 5 0 % of ril uz ol e-tre ate d p ati e nts will e x perie nc e at l east o ne A L T/ S G P T le vel 
a b o ve t he u p p er li mit of n or mal, a b o ut 8 % will h a ve ele vati o ns > 3 X U L N, a n d a b o ut 2 % of 
patie nts will ha v e el e vati o ns > 5 X U L N. A si n gle n o n -A L S patie nt wit h e pile ps y tre ate d wit h 
c o nc o mita nt car ba m aze pi ne a n d p h e n o bar bital e x perie nce d mar ke d, ra pi d el e vati o ns of li ver 
e nz y mes wit h ja u n di ce ( A L T 2 6 X U L N, A S T 1 7 X U L N, a n d bilir u bi n 1 1 X U L N) f o ur m o nt hs 
after starti n g ril uz ole; t hese r et ur ne d t o n or mal 7 wee ks after tre at m e nt disc o nti n uati o n. 
Ma xi m u m i n creases i n ser u m A L T us u all y o cc urre d wit hi n 3 m o nt hs after t h e start of ril uz ole 
t hera p y a n d were us uall y tr a nsie nt w he n < 5 ti m es U L N. I n trials, if A L T le v els were < 5 ti mes 
U L N, treat m e nt c o nti n ue d a n d A L T le v els us uall y r et ur ne d t o bel o w 2 ti m es U L N wit hi n 2 t o 6 
m o nt hs. Tre at me nt i n st u di es was disc o nti n ue d, h o w e ver, if A L T le vels e xcee d e d 5 X U L N, s o 
t hat t h ere is n o e x p erie nc e wit h c o nti n ue d treat me nt of A L S patie nts o nc e A L T val ues e xce e d 5 
ti mes U L N. T her e were rare i nsta nc es of ja u n di ce. T here is li mit e d e x perie nce wit h rec h all e n ge 
of patie nts w h o ha ve ha d ril uz ole disc o nti n u e d f or A L T > 5 X U L N, b ut t here is t he p ossi bilit y 
of i ncrease d A L T val ues re o cc urri n g. T heref or e, rec halle n g e is n ot re c o m m e n de d. I n p ost -
mar keti n g e x perie nce, cases of cli nic al he p atitis ass ociat e d  wit h ril uz ol e ha ve be e n re p ort e d, 
i ncl u di n g o n e wit h fatal o utc o m e. 
1. 1. 5. 2. 2  
N e utr o p e ni a  
T r oril uz ole has n ot b ee n ass ociate d wit h h e mat ol o gi c fi n di n gs i n n o ncli ni cal t o xic ol o g y st u dies 
t o date.  I n St u d y B H V 4 1 5 7-1 0 1, o ne s u bje ct i n t he 1 7. 5 m g BI D c o h ort e x perie nc e d tra nsie nt 
a n d mil dl y decr ease d w hite bl o o d cell c o u nt aft er t hr ee da ys of tre at me nt; h o we ver, t his s u bject 
e vi de nc e d m o derate de cli n e d uri n g t h e scree ni n g peri o d pri or t o m e dic ati o n a d mi nistrati o n.  T he 
s u bject’s c o u nt i ncre ase d w hile o n c o nti n ue d st u d y dr u g a n d n or malize d wit hi n 6 da ys aft er 
o nset.  
F or ril u z ole , acc or di n g t o t he U S PI, rare c ases of ne utr o pe nia wer e re p orte d. A m o n g 
a p pr o xi matel y 4, 0 0 0 p ati e nts gi ve n ril uz ol e f or A L S i n cli nical tri als, t her e were t hre e cases of 
mar ke d ne utr o pe ni a (a bs ol u te n e utr o p hil c o u nt less t ha n 5 0 0/ m m 3), all se e n wit hi n t he first 2 
m o nt hs of ril uz ole tr eat me nt. I n o ne case, ne utr o p hil c o u nts r ose o n c o nti n u e d tre at me nt. I n a 
sec o n d case, c o u nts r ose after t h era p y was st o p pe d. A t hir d cas e was m ore c o m ple x, wit h mar k e d 
a ne mi a as well as ne utr o pe ni a a n d t h e eti ol o g y of b ot h is u ncertai n. Pati e nts s h o ul d be war ne d t o 
re p ort a n y fe brile ill ness t o t heir p h ysicia ns. T he r e p ort of a fe brile ill ness s h o ul d pr o m pt treati n g 
p h ysicia ns t o c h ec k w hit e bl o o d cell c o u nts.  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1. 1. 5. 2. 3  
I nt er stiti al L u n g Di s e a s e 
T r oril uz ole has n ot b ee n ass ociate d wit h p ul m o nar y fi n di n gs i n n o ncli nic al t o xic ol o g y st u dies t o 
date.  
F or ril u z ole acc or di n g t o t he U S PI, rare c ases of i nterstitial l u n g dise ase ha ve b ee n re p ort e d, 
s o me of t he m se v ere; u p o n f urt her i n vesti gati o n, ma n y of t hese cases were h y perse nsiti vit y 
p ne u m o nitis. If res pirat or y s y m pt o ms de vel o p s uc h as dr y c o u g h a n d/ or d ys p nea, c hest 
ra di o gra p h y s h o ul d be p erf or me d, a n d i n case of fi n di n gs s u g gesti ve of i nt erstitial l u n g disease 
or h y perse nsiti vit y p n e u m o nitis (e. g., bilateral diff use l u n g o paciti es), ril uz ole s h o ul d be 
disc o nti n ue d i m m e diatel y. I n t he maj orit y of t he re p orte d cases, s y m pt o ms res ol ve d after dr u g 
disc o nti n uati o n a n d s y m pt o matic treat me nt. 
1. 1. 6  
P ot e nti al Ri s k t o F et al D e v el o p m e nt  
T r oril uz ole has n ot y et bee n assesse d i n fertilit y a n d fetal d e vel o p me nt st u dies.  
As descri be d i n t he U S PI, oral a d mi nistr ati o n of ril u z ole t o pr e g na nt a ni mals d uri n g t he p eri o d of 
or ga n o ge nesis ca use d e m br y ot o xi cit y i n rats a n d r a b bits at d oses of 2 7 m g/ k g a n d 6 0 m g/ k g, 
res pecti v el y, or 2. 6 a n d 1 1. 5 ti mes, res pe cti v el y, t h e rec o m m e n de d m a xi m u m h u ma n dail y d ose 
o n a m g/ m 2 b asis. E vi de n ce of m ater nal t o xi cit y was als o o bser ve d at t hese d oses. W he n 
a d mi nist ere d t o r ats pri or t o a n d d uri n g mati n g ( m ales  a n d fe males) a n d t hr o u g h o ut gestati o n a n d 
lact ati o n (f e males), ril uz ole pr o d uc e d a d verse effects o n pre g na nc y ( decr ease d i m pla ntati o ns, 
i ncrease d i ntra uteri ne d eat h) a n d offs pri n g via bilit y a n d gr o wt h at a n oral d ose of 1 5 m g/ k g or 
1. 5 ti mes t h e ma xi m u m d ail y d ose o n a m g/ m 2 basis. T here ar e n o a de q uate a n d well -c o ntr oll e d 
st u dies i n pre g na nt w o me n. Ril uz ol e s h o ul d be use d d uri n g pre g na nc y o nl y if t h e p ote ntial 
be nefit j ustifi es t he p ot e nti al ris k t o t he  fet us. 
1. 2  
St u d y  R ati o n al e  
1. 2. 1  
St u d y D e si g n R ati o n al e  
T r oril uz ole is a gl uta mate m o d ulati n g dr u g t h at is bei n g de vel o p e d f or t he p ote ntial tr eat me nt of 
s pi n ocere bellar ata xi a ( S C A) as well as O bsessi ve C o m p ulsi ve Dis or der ( O C D) . T his pr ot oc ol 
re prese nts t he first tri al of tr oril uz ol e i n O C D. 
T r oril uz ole is a n o v el tri pepti de pr o dr u g of t he gl uta mate m o d ulati n g a g e nt ril uz ole. T he 
pr o p ose d st u d y is base d o n rece nt precli nic al, cli ni cal , ge netic a n d n e ur oi ma gi n g st u dies t hat 
i m pli cat e gl ut a mater gic h y p eracti vit y i n t h e pat h o g e nesis of O C D 2 4 ,2 6 ,2 7 ,4 4. W hile  tr oril uz ol e has 
yet t o be st u die d i n O C D , st u dies wit h ril uz ole i n p o p ulati o ns wit h O C D pr o vi de s u p p ort f or t he 
t hera pe utic p ote ntial of tr oril uz ole. I n a d diti o n t o o pe n la bel d ata s u g gesti n g t he b e nefit of 
ril uz ol e i n i n di vi d uals wit h O C D 8 ,3 6 ,3 7, o ne  rece nt pl ace b o -c o ntr oll e d, d o u ble -bli n d tri al of 
ril uz ol e a ug m e ntati o n of S S RI treat me nt i n patie nts wit h refract or y or m o derate t o se v ere O C D 
s h o we d ril uz ole t o be effe cti v e i n a su bset of p ati e nts  4. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 8  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Ril uz ol e has se veral m o des of acti o n; pr o mi ne nt a m o n g t he m, ar e a re d ucti o n i n gl uta mat e 
o utfl o w d ue t o eff ects o n t h e e xcitat or y a mi n o aci d tr a n sp orters  3 8. Gi v e n t he e vi de nc e f or t he 
r ole of el e vat e d brai n gl uta m ate i n O C D, a n d t hat tr oril uz ol e is a pr o dr u g of ril uz ole, it is 
h y p ot hesize d t hat it w o ul d be e x pect e d t o ha v e t her a pe utic v al ue i n O C D as a gl uta mate 
m o d ulati n g a ge nt.  
T r oril uz ole was de vel o pe d t o a d v a nce u p o n t he li mit ati o ns of ril u z ole t hat h a ve restri cte d its 
br oa der cli nic al a p plicati o n. Ril uz ol e ta blets h a v e 6 0 % bi oa vaila bilit y, attri b ute d t o hi g h first -
pass meta b olis m i n t h e li v er. T his is t h o u g ht t o be r el ate d t o met a b olis m b y t he heter o ge ne o usl y 
e x presse d C Y P 1 A 2 e nz y me, w hic h is als o attri b uta bl e t o t he hi g h P K varia bilit y ass ociat e d wit h 
ril uz ol e 8 -1 0. I n a d diti o n, ril u z ole is ass oci ate d wit h re d uce d e x p os ure w he n ta k e n wit h m eals 
(i.e., a ne g ati v e f o o d effect), res ulti n g i n t h e g ui da n c e t o ta k e ril u z ole wit hi n a t hree h o ur fast 
( o ne h o ur bef ore or  t w o h o urs after a me al). 
Ril uz ol e is als o d ose d t wi ce a d a y, has d ose -de pe n de nt effects o n li ver f u ncti o n t ests a n d t he 
dr u g s u bsta nce itself has ot her i ntri nsic li mitati o ns i n cl u di n g: v er y l o w s ol u bilit y i n water, p o or 
oral pal ata bilit y, p H de pe n de nt c he mical sta bilit y a n d i nte nse oral n u m b ness if a d mi nist ere d 
directl y t o t h e oral m uc osa.  
T r oril uz ole is a t hir d ge ner ati o n of pr o dr u g d e vel o p me nt re pr ese nti n g m ulti ple y ears of 
c he mistr y eff ort wit h o pti mize d i n vi v o a n d i n vitr o f eat ures base d o n st a bilit y w hil e tra nsiti n g 
t he di gesti ve s yste m, e n ha nce d g astr oi nt esti nal a bs or pti o n, a v oi d a nce of first pass meta b olis m, 
fa v ora ble safety p har m ac ol o g y, met a b oli c cl ea va g e i n t he plas m a, a n d e n h a nce d 
p har mac o ki netic pr o perties.  
Base d o n t he pre cli nical f eat ur es of tr oril u z ole, we a ntici p ate t he cli ni cal p har mac ol o g y t o offer 
fa v ora ble pr o p erties as c o m pare d t o a vaila ble ril uz ol e: 
•  Im pr o ve d Bi o a v ail a bilit y — T r oril u z ole is a s u bstrat e f or t he g ut tra ns p orters ( Pe p T 1). T his 
is t h o u g ht t o i n crease t he bi o a vaila bilit y of t h e dr u g as c o m pare d t o orall y d ose d ril uz ole, 
mea ni n g t hat m ore of t h e c o m p o u n d is a bs or be d b y t he b o d y i nt o t h e bl o o d stre a m a n d ca n 
ha ve a n a cti v e effect. St u dies ha v e s h o w n t hat a d mi nistrati o n of a ge nts t hr o u g h p e pti d e 
tra ns p orters si g nifi ca ntl y i ncre ases t he a bs or pti o n of dr u gs wit h ot her wise p o or oral 
bi oa vaila bilit y.  
•  N o Ne g ati ve F o o d Effect — T r oril uz ol e s h o ws n o f o o d effect i n h u ma n st u dies, mea ni n g t hat 
t he dr u g will n ot be ass oci ate d wit h s pecial me al restricti o ns, a p h e n o me n o n p ote ntiall y 
attri b uta bl e t o e n h a n ce d u pt a ke b y i ntesti n al tr a ns p orters s pecifi c t o t h e pe pti de -c o nt ai ni n g 
m oiet y of tr o ril u z ole. T his is i n c o ntrast t o oral ril u z ole ta blets, w hic h r e q uire a 3-h o ur 
wi n d o w of fasti n g ar o u n d its t w o dail y d oses t o re ac h t hera pe utic le vels, c urr e ntl y a d ose -
li miti n g fa ct or of ril uz ol e. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 2 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
•  L o wer O ver all Dr u g B ur de n t o t he Li ver — As a pr o dr u g t hat miti g ates first -p ass li ver 
meta b olis m a n d e n ha nces bi oa vaila bilit y, t hera p e uti c c o nce ntr ati o ns of t h e acti ve m eta b olit e 
ril uz ol e ca n b e ac hi e ve d wit h a l o wer m olar dr u g lo a d  as c o m pare d t o ril u z ole t a blets. I n 
a d diti o n, r ele ase of t he a cti v e meta b olite o v er ti me will res ult i n a r e d uce d b ol us he pati c 
c o nce ntr ati o n as c o m pare d t o t hat ass ociate d wit h ril uz ole t a blets. Ta ke n t o get her, we b eli e ve 
t hese attri b ut es of tro ril u z ole will re d uc e t he p ote ntial f or a d verse li ver effe cts. 
•  O pti mize d D osi n g Re gi me n a n d C o m pli a nce — T r oril uz ol e has bee n d e vel o pe d as a 
c o n ve nie nt o nce -dail y d ose, w hic h c o ul d i m pr o ve re gi me n c o m pli a nce f or patie nts. We 
belie v e t hese are i m p orta nt f eat ur es t o o pti miz e l o n g -ter m he alt h o utc o m es i n t he treat me nt 
of patie nts wit h c hr o ni c diseases.   
1. 2. 2  
P h ar m a c o ki n eti c s a n d D o s e S el e cti o n R ati o n al e  
1. 3  
R e s e ar c h H y p ot h e si s  
T r oril uz ole is s u peri or t o plac e b o as a dj u n cti v e t her a p y w he n a d de d t o Sta n d ar d of Care 
Treat me nt o v er a 1 2 wee k peri o d i n patie nts wit h O bsessi ve C o m p ulsi ve Dis or der wit h a n 
i na de q uate res p o nse t o S S RI, cl o mi pra mi ne, ve nlafa xi ne or des ve nl afa xi ne treat me nt. 
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 3 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
2  S T U D Y O B J E C TI V E S  
2. 1  
Pri m ar y  
•  T he pri m ar y o bje cti ve of t he st u d y is t o e val u ate t he effica c y of tr oril u z ole as a dj u ncti ve 
t hera p y i n s u bj ects wit h O C D w h o ha ve ha d a n i na de q uate res p o nse t o S S RI , cl o mi pra mi ne, 
ve nlafa xi ne or des ve nl afa xi n e  tre at m e nt  
2. 2  
S e c o n d ar y  
•  T o assess t he safet y a n d t olera bilit y of tr oril uz ol e, rel ati ve to pla ce b o, i n s u bj ects wit h O C D  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n f u ncti o n al disa bilit y  as me as ure d 
b y t he S D S  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n gl o bal f u n cti o ni n g as me as ure d 
b y t he Cli nical Gl o bal I m pressi o n - Se verit y Scale  ( C GI-S ) 
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n o bsessi ve s y m pt o mat ol o g y as 
meas ure d b y t h e c ha n ge i n t he Y -B O C S o bsessi o ns s u bscale  
2. 3  
E x pl or at or y  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n de pressi ve s y m pt o mat ol o g y as 
meas ure d b y t h e QI D S -S R  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d t o plac e b o o n a n xiet y s y m pt o ms as m eas ure d 
b y t he B AI  
•  E val uate t h e effic ac y of tr oril uz ole c o m pare d to plac e b o o n i nsi g ht re g ar di n g o bsessi o nal 
beliefs as m eas ure d b y t he B A B S  
•  T o assess p har mac o d y na mic eff ects of tr oril uz ole vs. place b o o n mar kers of s y na pti c 
plasticit y  as m eas ure d b y pl as ma le v els of B D N F a n d pr o B D N F  
•  T o c hara cteri ze t h e p har m ac o ki n eti cs of tr oril u z ole b ase d o n s parse sa m pli n g  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 3 1  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
3  S T U D Y E N D P OI N T S  
3. 1  
Pri m ar y  
•  I m pr o ve me nt i n o bsessi ve-c o m p ulsi ve s y m pt o mat ol o g y is assesse d usi n g t he c ha n ge i n t he 
Yale -Br o w n O bsessi ve C o m p ulsi ve Scale ( Y -B O C S) t otal sc or e fr o m base li ne t o t he e n d of 
t he d o u ble-bli n d p hase of t he st u d y  (W e e k 1 2 ).  
3. 2  
S e c o n d ar y  
•  Safet y a n d t olera bilit y are assesse d usi n g t he fr e q ue n c y of u ni q ue s u bje cts wit h: seri o us 
a d verse e ve nts; a d verse e v e nts le a di n g t o disc o nti n u ati o n; a d verse e v e nts j u d ge d t o b e re l ate d 
t o st u d y me di cati o n; a n d cli nicall y si g nifica nt la b orat or y a b n or malities t hat are o bser ve d 
d uri n g t he d o u bl e -bli n d p h ase.  
•  I m pr o ve me nt i n f u ncti o nal disa bilit y is assesse d usi n g t he c ha n g e i n t h e S hee ha n Disa bilit y 
Scale ( S D S) t otal sc or e fr o m baseli ne t o t he e n d of t he d o u ble -bli n d p hase.  
•  I m pr o ve me nt i n gl o b al cli ni cal c o n diti o n is assesse d usi n g t he Cli nical Gl o bal I m pressio n of 
Se verit y  Scale ( C GI-S ) at t h e e n d of t he d o u ble-bli n d p hase of t he st u d y.  
•  I m pr o ve me nt i n o bsessi ve s y m pt o mat ol o g y is assesse d usi n g t he c h a n ge i n t he Y-B O C S 
o bsessi o ns s u bscale sc ore fr o m baseli ne t o t h e e n d of t he d o u ble -bli n d p hase of t he st u d y.  
3. 3  
E x pl or at or y  
•  I m pr o ve me nt i n de pr essi ve s y m pt o m at ol o g y is meas ure d b y t he c h a n ge i n t he Q uic k 
I n ve nt or y of D e pressi ve S y m pt o mat ol o g y-Self Re p ort ( QI D S -S R)  fr o m baseli ne t o t h e e n d 
of t he d o u ble -bli n d p hase.  
•  I m pr o ve me nt i n a n xiet y is assesse d usi n g t he c ha n ge i n t he Be c k A n xiet y I n v e nt or y ( B AI) 
fr o m baseli n e t o t h e e n d of t he d o u ble bli n d p hase. 
•  I m pr o ve me nt of i nsi g ht i nt o o bsessi ve-c o m p ulsi ve b eliefs is m eas ure d b y t h e c ha n ge i n t he 
Br o w n Assess me nt of Beli efs Scale ( B A B S) fr o m baseli ne t o t he e n d of t he d o u b l e-bli n d 
p hase.  
•  T he i m p act o n mar kers of s y na pti c plasticit y is assesse d usi n g t he c ha n g e i n pl as ma B D N F 
a n d pr o B D N F le vels fr o m baseli ne t o t he e n d of t h e d o u ble -bli n d p h ase.  
•  T h e p h ar m a c o ki n eti c  pr ofil e of tr oril uz ol e is c h ar a ct eri z e d b y bl o o d c o n c e ntr atio ns 
o bs er v e d i n tr e at e d s u bj e cts . 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 32 of 97 
 
Draft Version 10; 13 Oct 2022 
 
4 STUDY PLAN 
4.1 
Study Design and Duration 
BHV4157-202 is a Phase IIb/III, multicenter, randomized, double-blind, 2-arm placebo- 
controlled parallel-group study designed to assess safety, tolerability, and efficacy of troriluzole 
as adjunctive therapy in a population of patients with Obsessive Compulsive Disorder who have 
had an inadequate response to Standard of Care treatment. Treatment failure on the subjects’ 
current standard of care is defined by a Yale–Brown Obsessive Compulsive Scale (Y-BOCS) 
score of 19 or greater despite at least 8 weeks of treatment at Screening and 10 weeks of 
treatment, at Baseline, with an adequate dose of an SSRI, clomipramine, venlafaxine or 
desvenlafaxine medication.  
Subjects who are stable on Standard of Care (SOC) medication and are having an inadequate 
response (as defined above) will be randomized to additionally receive once a day dosing of  
troriluzole or matching placebo. 
Subjects will receive either troriluzole (140mg) or Placebo for the first four weeks and then will 
be increased to 200 mg (or matching placebo) for the duration of the study.  Down titration after 
the first four weeks of the Randomization Phase will only be allowed for tolerability purposes.    
Dosing will continue for approximately 12 weeks. Subjects will return to the clinic two weeks 
after discontinuing study medication for a follow-up safety visit. In addition, subjects completing 
the Randomization Phase will be offered approximately 48 weeks of open-label treatment as 
long as the PI believes open-label treatment offers an acceptable risk-benefit profile. Subjects 
who agree to enter the Extension Phase will not complete the follow-up safety visit and should 
continue dosing as specified. 
Subjects entering the Extension Phase will have their first Extension Visit four weeks after the 
Week 12 Randomization Phase visit. Thereafter, subjects will undergo visits every four weeks up 
through week 12 of the Extension Phase as outlined in Table 2 (Schedule of Assessments/Time 
& Events- Extension Phase). Subjects will then undergo visits every 12 weeks up to Week 48 of 
the Extension phase. All subjects will undergo a termination visit two weeks after the last dose of 
study drug. 
Subjects entering the Extension Phase will continue with the same dose taken at the end of the 
Randomization Phase. Subjects on placebo in the Randomization Phase will be switched in a 
blinded manner to 140 mg for the first four weeks and then will be increased to 200 mg for the 
duration of the study. Down titration after the first four weeks of the Extension Phase will only 
be allowed for tolerability purposes.  All Visits after week 4 will be open label.  Subjects who 
enter the Extension Phase on 140 mg due to tolerability issues can be rechallenged to increase to 
200 mg after Extension Week 4 at PI discretion.    
Subjects who complete the 48-week Extension Phase and are continuing directly into the 48-
week Expanded Extension Phase with no dose interruption will have their first visit 12 weeks 
after the Extension Week 48 visit. Therafter, subject will undergo visits every 12 weeks until 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 33 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Week 96 of the Expanded Extension Phase as outlined in Table 3 (Schedule of 
Assessments/Time and Events – Expanded Extension Phase – Continuing Subjects).  
Subjects who previously completed the Extension Week 48 visit and exited the study, will have 
the opportunity to return and receive an additional 48 weeks of open-label treatment with 
troriluzole provided it has not been more than 3 months since they completed the study and the 
PI believes it offers an acceptable risk-benefit profile. Returning subjects who have been off 
study medication for less than 4 weeks will undergo an abbreviated Baseline visit before re-
entering the study. Returning subjects who have been off study medication for 4 weeks or more 
will be required to undergo a full Baseline visit. In addition, for returning subjects, safety 
laboratory assessments will be performed 4 and 8 weeks after re-starting study medication. 
Thereafter, study visits in the Expanded Extension Phase will be every 12 weeks until Week 48 
of the Expanded Extension Phase as outlined in Table 4 (Schedule of Assessments/Time and 
Events – Expanded Extension Phase – Returning Subjects). All subject will undergo a 
termination visit two weeks after the last dose of study drug. 
Subjects entering the Expanded Extension Phase will continue with the same dose taken at the 
end of the initial Extension Phase. Down titration after the first four weeks of the Expanded 
Extension Phase will only be allowed for tolerability purposes.  Subjects who enter the Expanded 
Extension Phase on 140 mg due to tolerability issues can be rechallenged to increase to 200 mg 
after the first 4 weeks at PI discretion.    
Subjects who complete the 48-week Expanded Extension Phase and are continuing directly into 
the 96-week Additional Expanded Extension Phase with no dose interruption will have their first 
visit 12 weeks after the 48th week of the Expanded Extension (EE Week 96 or EE Week 48 as 
identified in protocol version 08). Therafter, subject will undergo visits every 12 weeks until 
Week 96/144/192 of the Additional Expanded Extension Phase as outlined in Table 5 and Table 
7 (Schedule of Assessments/Time and Events – Additional Expanded Extension Phase – 
Continuing Subjects).  
Subjects who previously completed the Expanded Extension Week 48/96 visit and exited the 
study, will have the opportunity to return and receive an additional 48 weeks of open-label 
treatment with troriluzole provided it has not been more than 4 weeks since they completed the 
study and the PI believes it offers an acceptable risk-benefit profile. Returning subjects will 
undergo an abbreviated Baseline visit before re-entering the study. In addition, for returning 
subjects, safety laboratory assessments will be performed 4 and 8 weeks after re-starting study 
medication. Subjects who complete the initial 48 weeks of the Additional Expanded Extension 
Phase will have the opportunity to continue and receive an additional 48 weeks of open-label 
treatment provided the PI believes it offers an acceptable risk-benefit profile. Thereafter, study 
visits in the Additional Expanded Extension Phase will be every 12 weeks until Week 96 of the 
Additional Expanded Extension Phase as outlined in Table 6 (Schedule of Assessments/Time 
and Events – Additional Expanded Extension Phase – Returning Subjects). All subject will 
undergo a termination visit two weeks after the last dose of study drug. 
Subjects entering the Additional Expanded Extension Phase will continue with the same dose 
taken at the end of the Expanded Extension Phase. Down titration after the first four weeks of the 
Expanded Extension Phase will only be allowed for tolerability purposes.  Subjects who enter the 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 34 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Additional Expanded Extension Phase on 140 mg due to tolerability issues can be rechallenged 
to increase to 200 mg after the first 4 weeks at PI discretion.    
Subjects will be assessed at clinic visits per the Schedule of Assessments/Time & Events. 
4.2 
Study Schematic 
Figure 1:  
Study Schematic 
     
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole  ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der 
Pa ge 3 5  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
4. 3  
S c h e d ul e of A s s e s s m e nt s  
E ver y eff ort s h o ul d b e ma de t o  c o n d uct t he st u d y visits as pla n ne d. H o we ver, d u e t o c o nc er ns 
relat e d t o t h e C O VI D-1 9 pa n de mic, st u d y partici pa nts ma y be u na bl e t o c o me i nt o t he offi ce f or 
t heir st u d y sc he d ule d visit, i n or der t o mi ni mi ze a n y p ote nti al ris ks t o st u d y partici pa nt saf et y 
a n d t o c o m pl y wit h g o ver n me nt al a n d l ocal i nstit uti o nal g ui da n ce (e. g., st u d y site has a p olic y 
t hat a cli nical researc h visit m ust b e del a ye d) n ot e t h e f oll o wi n g g ui d a nce : U n der t hese 
circ u mst a nces, t h e i n vesti gat or s h o ul d c o ntact t he s p o ns or me dical m o ni t or t o disc uss t he m ost 
a p pr o priat e c o urse of acti o n. Re m ote saf et y visits will be all o we d o n a case b y case b asis, if a 
patie nt is u na bl e t o c o me t o t he site f or e val u ati o n  a n d t he i n vesti gat or d eter mi nes t hat a re m ote 
visit offers a n a cce pt a ble ris k -be ne fit a p pr oa c h a n d is a p pr o priate f or a parti c ular s u bj ect. T he 
i n vesti gat or s h o ul d disc uss t he s pecific re q uire m e nts f or t he re m ote safet y visit wit h t he s p o ns or 
me dic al m o nit or, w hic h will be b ase d o n t he st u d y visit n u m ber a n d t he cli ni cal st at us of t he 
p artici pa nt. If t he re m ote visit re q uir es la b orat or y testi n g, l oc al l a bs m ust be a ble t o b e o btai n e d, 
re vie we d b y t h e site  a n d a re da cte d v ersi o n f or war de d t o Bi o ha ve n w he n a vaila ble f or r e vie w.  
S hi p pi n g of st u d y dr u g fr o m t he site t o t he patie nt vi a o ver n i g ht trac k e d a n d certifi e d c o uri er will 
als o be all o we d.  
 
S p o ns or Me dic al M o nit or  
Cell:
 
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 36 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 1: 
Schedule of Assessments and Events - Randomization Phase 
 
Visit 
 
Screeninga 
 
Baseline 
 
Week 
2 
 
Week  
4 
 
Week 
6 
 
Week  
8 
Week 12 
or early 
termbc 
Week 2 
Post Last 
Dosed 
Day 
-2 to -42 
0 
 
28 
 
56 
84 
98 
Eligibility Assessments 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Pharmacogenetic Informed Consent 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
MINI 
X 
 
 
 
 
 
 
 
MMSE 
X 
 
 
 
 
 
 
 
Borderline Personality Disorder Module (BPD 
Module) 
X 
 
 
 
 
 
 
 
MGH-TRQ-OCDe 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Demographic Assessment 
X 
 
 
 
 
 
 
 
Disease History 
X 
 
 
 
 
 
 
 
SAFER Interviewf 
X 
 
 
 
 
 
 
 
Safety Assessments 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
 
X 
 
X 
X 
X 
Telephone Check-inm 
 
 
X 
 
X 
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 37 of 97 
 
Draft Version 10; 13 Oct 2022 
 
 
Visit 
 
Screeninga 
 
Baseline 
 
Week 
2 
 
Week  
4 
 
Week 
6 
 
Week  
8 
Week 12 
or early 
termbc 
Week 2 
Post Last 
Dosed 
Day 
-2 to -42 
0 
 
28 
 
56 
84 
98 
Includes AE assessment and concomitant medication 
review 
Laboratory Assessments including urinalysisg 
X 
X 
 
X 
 
X 
X 
 
Serologyh 
X 
 
 
 
 
 
 
 
Pregnancy testingi 
X 
X 
 
X 
 
X 
X 
 
Urine drug testj 
X 
X 
 
 
 
 
X 
 
Physical Exam 
X 
 
 
 
 
 
X 
 
Physical Measurements 
X 
 
 
 
 
 
X 
 
Vital Signs 
X 
X 
 
X 
 
X 
X 
X 
12-Lead ECG 
X 
X 
 
 
 
 
X 
 
Concomitant Medication Review 
X 
X 
 
X 
 
X 
X 
X 
Sheehan Suicidality Tracking Scale (STS) 
X 
X 
 
X 
 
X 
X 
X 
Clinical Outcome Assessments 
 
 
 
 
 
 
 
 
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) 
X 
X 
 
X 
 
X 
X 
 
Clinical Global Impressions-Severity Scale (CGI-S) 
X 
X 
 
X 
 
X 
X 
 
Sheehan Disability Scale (SDS)n 
X 
X 
 
X 
 
X 
X 
 
Quick Inventory of Depressive Symptomatology-Self 
Report (QIDS-SR) 
X 
X 
 
X 
 
X 
X 
 
Beck Anxiety Inventory (BAI) 
X 
X 
 
X 
 
X 
X 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 38 of 97 
 
Draft Version 10; 13 Oct 2022 
 
 
Visit 
 
Screeninga 
 
Baseline 
 
Week 
2 
 
Week  
4 
 
Week 
6 
 
Week  
8 
Week 12 
or early 
termbc 
Week 2 
Post Last 
Dosed 
Day 
-2 to -42 
0 
 
28 
 
56 
84 
98 
Brown Assessment of Beliefs (BABS) 
X 
X 
 
 
 
 
X 
 
Biomarker and Other Assessments 
 
 
 
 
 
 
 
 
BDNF and proBDNF Blood Sample 
 
X 
 
 
 
 
X 
 
Pharmacokinetics Blood Samplek 
 
 
 
X 
 
X 
X 
 
Pharmacogenomics Blood Sample 
 
X 
 
 
 
 
X 
 
Clinical Drug Supply 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Dispense Study Drugl 
 
X 
 
X 
 
X 
Xb, o 
 
Drug Accountability 
 
 
 
X 
 
X 
X 
 
 
*Visit Window is +/- 2 days during the Randomization Phase 
a Screening window is minimum of 2 days to maximum of 42 days. Screening can be as short as 2 days as long as the subjects has been on at least 8 weeks of 
their current SOC OCD therapy at an adequate dose at Screening and at least 10 weeks of their current SOC OCD therapy (SSRI, clomipramine, venlafaxine or 
desvenlafaxine) at an adequate dose by the Baseline Visit. 
b Study drug will be dispensed at Week 12 if subject is deemed eligible and agreed to participate in the Extension Phase. Subjects will not be allowed to transition 
to the Extension Phase until they have an in-person Week 12 visit. 
cEvery effort should be made to conduct the Week 12 visit and maintain the +/- 7 day window. However, due to concerns related to the COVID-19 pandemic, the 
Week12 visit window may be modified beyond the +/- 7 day window, in order to minimize any potential risks to study participant safety and to comply with 
governmental and local institutional guidance (e.g., study site has a policy that a clinical research visit must be delayed) note the following guidance. Under these 
circumstances, the last visit window may be extended up to 6 weeks (up to a maximum treatment duration of 18 weeks), but every attempt should be made to 
conduct the visit as close to the date the visit is due as possible. If the visit window is modified, and the investigator determines that a remote visit offers an 
acceptable risk-benefit approach and is appropriate for a particular subject, participants should be evaluated remotely for safety only (e.g., via phone) at the time 
of the scheduled Week 12 visit to perform and document appropriate safety assessments including the Sheehan Suicidality Tracking Scale (STS). If the remote 
visit requires laboratory testing, local labs must be able to be obtained, reviewed by the site and a redacted copy submitted to the study Medical Monitor.  Study 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 3 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
me dicati o n ma y be s e nt t o t he partici pa nt via trac ke d a n d certifie d c o urier. F or a n y s uc h cases, t he i n vesti gat or s h o ul d dis c uss t he s pecific circ u msta nces of eac h 
cas e wit h t he s p o ns or me dical m o nit or: 
; C ell
d   O nl y  f or s u bjects N O T e nteri n g t he E xte nsi o n P has e.  S u bjects e nteri n g t he E xte nsi o n P has e will n ot re q uire t he 2 -wee k p ost d os e visit.  
e  T he s u bject m ust ha ve a n i na de q uate res p o ns e t o t he sta n dar d of care treat me nt, as defi ne d i n t he pr ot oc ol . T he M G H -T R Q -O C D will be us e d t o ca pt ure 
i nf or mati o n o n past treat me nts. 
f  T he  S A F E R I nter vie w will be c o n d ucte d re m otel y wit h t he s u bject b y a C R O s h ortl y after t he s cree ni n g visit.  A S A F E R pass is nece ssar y f or ra n d o mizati o n. 
g   La b orat or y assess me nts are n ot re q uire d t o be fasti n g.   
h   H Bs A g, H C V , HI V a nti b o d y , R P R 
i Ser u m pre g na nc y test ( b -hc g) c o n d ucte d at s cree ni n g. Uri ne pre g na nc y test c o n d ucte d at s u bs e q ue nt visits. T o be d o ne p ri or t o d osi n g at bas eli ne.  T he site ma y 
test a patie nt at a n y ti me if pre g na nc y is s us pecte d. 
jUri ne dr u g test t o be c o n d ucte d at s cree ni n g, bas el i ne a n d E O S visit a n d at u ns c he d ule d visit at t he dis creti o n of t he i n vesti gat or.  R efle x c o nfir mat or y dr u g 
testi n g will be c o n d ucte d b y t he la b ve n d or f or all p ositi ve uri ne dr u g s cree n s a m ples. 
k  Plas ma sa m ples f or P K will be c ollecte d at ra n d o m at Wee k s 4 , 8  a n d 1 2 .  Date a n d ti me of d os es o n t he da y of visits a n d da y pri or will be c ollecte d i n cas e 
re p ort f or ms al o n g wit h ti me of last meal. P K s a m ples s h o ul d als o be dra w n w he n t here are a n y S A Es or s e vere A Es t hat are p ossi bly  dr u g relate d.  S u bjects w h o  
are a ble t o s c h e d ule a m or ni n g visit f or Wee k 4 a n d Wee k 8  ca n be i nstr ucte d t o h ol d t heir d os e of st u d y dr u g t hat m or ni n g u ntil after a P K tr o u g h s a m ple is 
o btai ne d, if p ossi ble a n d a p pr o priate . 
l St u d y Dr u g will be dis pe ns e d at t he bas eli ne visit. S u bje cts s h o ul d ta ke t he first d os e i n t he m or ni n g t he da y after t he bas eli ne visit.    
m  T ele p h o ne calls t o s u bjects will be ma de bet wee n visits d uri n g t he first a n d s ec o n d m o nt hs of t he R a n d o mizati o n P has e ( Wee ks 2 a n d 6) t o m o nit or s u bject 
c o n diti o n, a n y ne w c o nc o mita nt me dicati o ns  a n d a d verse e ve nts.  
n If a s u bject c hec ks t he “ n ot w or ki n g” b o x f or t he W or k/ Sc h o ol ite m o n t he S D S , y o u M U S T 
c hec k c o m plia nce t o t his i nstr ucti o n, bef ore t he visit e n ds.  
o If t he st u d y site nee ds t o s e n d dr u g o ver ni g ht via certifie d a n d trac ke d c o urier a n d t his is acce pta ble t o t he i nstit uti o n be ca us e a visit is a bs ol utel y n ot p ossi ble 
beca us e of t he C O VI D -1 9 pa n de mic, t his is per missi ble per st u d y. T he s p o ns or s h o ul d be c o n s ulte d pri or t o s hi p pi n g dr u g.  
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 40 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 2: 
Schedule of Assessments and Events - Extension Phase 
Visit 
Ext 
Wk 2 
Ext
Wk4 
Ext 
Wk 6 
Ext 
Wk 8 
Ext 
Wk 
12 
Ext
Wk 
24 
Ext 
Wk 
36 
Ext 
Wk 48 
or 
early 
term 
Wk2 Post last 
dose 
Safety Assessments 
 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
 
X 
 
X 
X 
X 
X 
X 
X 
Telephone Check-inb 
Includes AE assessment and concomitant 
medication review 
X 
 
X 
 
 
 
 
 
 
Laboratory Assessments 
 
X 
 
X 
X 
X 
X 
X 
 
Pregnancy testinga 
 
X 
 
X 
X 
X 
X 
X 
 
Urine drug test 
 
X 
 
X 
X 
X 
X 
X 
 
Physical Exam 
 
 
 
 
 
 
 
X 
 
Physical Measurements 
 
 
 
 
 
X 
 
X 
 
Vital Signs 
 
X 
 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
 
X 
 
 
X 
X 
X 
X 
 
Concomitant Medication Review 
 
X 
 
X 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking Scale 
(STS) 
 
X 
 
X 
X 
X 
X 
X 
X 
Clinical Outcome Assessments 
 
 
 
 
 
 
 
 
 
Yale-Brown Obsessive Compulsive 
Scale (Y-BOCS) 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Clinical Global Impressions-
Severity Scale (CGI-S) 
 
X 
 
X 
X 
X 
X 
X 
 
Sheehan Disability Scale 
(SDS)c 
 
X 
 
X 
X 
X 
X 
X 
 
Quick Inventory of Depressive 
Symptomatology-Self Report 
(QIDS-SR) 
 
X 
 
X 
X 
X 
X 
X 
 
Beck Anxiety Inventory (BAI) 
 
X 
 
X 
X 
X 
X 
X 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 41 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Brown Assessment of Beliefs 
(BABS) 
 
X 
 
 
X 
 
 
 
 
Biomarker and Other Assessments 
 
 
 
 
 
 
 
 
 
BDNF and proBDNF Blood Sample 
 
 
 
 
 
 
 
X 
 
Clinical Drug Supply 
 
 
 
 
 
 
 
 
 
Dispense Study Drug 
 
X 
 
X 
X 
X 
X 
 
 
Drug Accountability 
 
X 
 
X 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the extension phase.  
aIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Extension Phase. *Note: test will be sent home at 
Week 12 and at Week 24 and should be performed once between each visit. Subjects should be instructed to contact 
the study doctor if they become pregnant at any time during the study. Site should also contact the subject in 
between the 3-month office visits to remind them of the pregnancy testing requirement, as applicable.  
b Telephone calls to subjects will be made between visits during the first and second months of the Extension Phase 
(Weeks 2 and 6) to monitor subject condition, any new concomitant medications and adverse events. 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 42 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 3: 
Schedule of Assessments and Events – Expanded Extension Phase 
(continuing subjects) 
Visit 
Exp Ext 
Wk 60 
Exp Ext 
Wk 72 
Exp Ext 
Wk 84 
Exp Ext 
Wk 96 or 
early term 
Wk2 Post 
last dose 
Safety Assessments 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
Laboratory Assessments 
 
X 
 
X 
 
Labs: LFT tests only: (ALT, AST, BILI, GGT) 
X 
 
X 
 
 
Pregnancy testinga 
X 
X 
X 
X 
 
Urine drug test 
X 
X 
X 
X 
 
Physical Exam 
 
X 
 
X 
 
Physical Measurements 
 
X 
 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
X 
 
Concomitant Medication Review 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking Scale (STS) 
X 
X 
X 
X 
X 
Clinical Outcome Assessments 
 
 
 
 
 
Yale-Brown Obsessive Compulsive Scale (Y-
BOCS) 
 
X 
 
X 
 
X 
 
X 
 
 
Clinical Global Impressions-Severity Scale 
(CGI-S) 
X 
X 
X 
X 
 
Sheehan Disability Scale (SDS)b 
X 
X 
X 
X 
 
Clinical Drug Supply 
 
 
 
 
 
Dispense Study Drug 
X 
X 
X 
 
 
Drug Accountability 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the expanded extension phase.  
aIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Expanded Extension Phase. *Note: test will be sent 
home at Week 60, Week 72  and at Week 84 and should be performed once between each visit. 
b If a subject checks the “not working” box for the Work/School item on the SDS, you MUST 
check compliance to this instruction, before the visit ends. 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 43 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 4: 
Schedule of Assessments and Events – Expanded Extension Phase 
(returning subjects) 
Visit 
Baseline 
Visita 
Abbreviated 
Baseline 
Visitb 
Exp 
Ext Wk 
4 
Exp 
Ext Wk 
8 
Exp 
Ext 
Wk 12 
Exp 
Ext 
Wk 24 
Exp 
Ext Wk 
36 
Exp Ext 
Wk 48 / 
early 
term 
Wk2 
Post last 
dose 
Eligibility Assessments 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
X 
 
 
 
 
 
 
 
Safety Assessments 
 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
X 
 
 
 
 
X 
 
X 
 
Lab: LFT tests only (ALT, 
AST, BILI, GGT) 
 
 
X 
X 
X 
 
X 
 
 
Pregnancy testingc 
X 
 
 
 
X 
X 
X 
X 
 
Urine drug test 
X 
 
 
 
X 
X 
X 
X 
 
Physical Exam 
X 
 
 
 
 
X 
 
X 
 
Physical Measurements 
X 
 
 
 
X 
X 
X 
X 
 
Vital Signs 
X 
X 
 
 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
 
 
 
X 
X 
X 
X 
 
Concomitant Medication 
Review 
X 
X 
 
 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking 
Scale (STS) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Outcome 
Assessments 
 
 
 
 
 
 
 
 
 
Yale-Brown Obsessive 
Compulsive Scale (Y-
BOCS) 
X 
 
 
 
X 
X 
X 
X 
 
Clinical Global Impressions-
Severity Scale (CGI-S) 
X 
 
 
 
X 
X 
X 
X 
 
Sheehan Disability Scale 
(SDS)d 
X 
 
 
 
X 
X 
X 
X 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 44 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Clinical Drug Supply 
 
 
 
 
 
 
 
 
 
Re-enter subject in IWRS 
X 
X 
 
 
 
 
 
 
 
Dispense Study Drug 
X 
X 
 
 
X 
X 
X 
 
 
Drug Accountability 
 
 
X 
X 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the expanded extension phase. 
aBaseline Visit is needed for returning subjects who completed dosing in the initial Extension Phase ≥ 4 weeks prior 
to returning to the study and entering the Expanded Extension Phase.  
bAbbreviated Baseline Visit only needed for returning subjects who completed dosing in the initial Extension Phase 
< 4 weeks prior to returning to the study and entering the Expanded Extension Phase.  
cIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Expanded Extension Phase. *Note: A test will be sent 
home at Week 12, 24 and at Week 36 and should be performed once between each visit. 
d If a subject checks the “not working” box for the Work/School item on the SDS, you MUST 
check compliance to this instruction, before the visit ends. 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 45 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 5: 
Schedule of Assessments and Events – Additional Expanded 
Extension Phase (continuing subjects) 
Visit 
Add’l Exp 
Ext 
Wk 
60/108 
Add’l Exp 
Ext 
Wk 
72/120 
Add’l Exp 
Ext         
Wk 
84/132 
Add’l Exp 
Ext 
Wk 96/144 
or early 
term 
Wk2 
Post last 
dose 
Safety Assessments 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
Laboratory Assessments 
 
X 
 
X 
 
Labs: LFT tests only: (ALT, AST, BILI, GGT) 
X 
 
X 
 
 
Pregnancy testinga 
X 
X 
X 
X 
 
Urine drug test 
X 
X 
X 
X 
 
Physical Exam 
 
X 
 
X 
 
Physical Measurements 
 
X 
 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
X 
 
Concomitant Medication Review 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking Scale (STS) 
X 
X 
X 
X 
X 
Clinical Outcome Assessments 
 
 
 
 
 
Yale-Brown Obsessive Compulsive Scale (Y-
BOCS) 
X 
X 
X 
X 
 
Clinical Global Impressions-Severity Scale 
(CGI-S) 
X 
X 
X 
X 
 
Sheehan Disability Scale (SDS)b 
X 
X 
X 
X 
 
Clinical Drug Supply 
 
 
 
 
 
Dispense Study Drug 
X 
X 
X 
Xc 
 
Drug Accountability 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the additional expanded extension phase.  
aIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Additional Expanded Extension Phase. *Note: test will 
be sent home at Week 60/108, Week 72/120  and at Week 84/132 and should be performed once between each visit. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 46 of 97 
 
Draft Version 10; 13 Oct 2022 
 
b If a subject checks the “not working” box for the Work/School item on the SDS, you MUST 
check compliance to this instruction, before the visit ends. 
c Only subjects continuing in the Additional Expanded Extension Phase for an additional 48 weeks of Open-Label 
treatment will be dispensed IP at this visit.  
 
Table 6: 
Schedule of Assessments and Events – Additional Expanded 
Extension Phase (returning subjects) 
Visit 
Abbreviated 
Baseline 
Visita 
Add’l 
Exp Ext 
Wk 4 
Add’l 
Exp Ext 
Wk 8 
Add’l 
Exp Ext 
Wk 12 
Add’l 
Exp Ext 
Wk 24 
Add’l 
Exp Ext 
Wk 36 
Add’l 
Exp Ext 
Wk 48 / 
early 
term 
Wk2 
Post last 
dose 
Eligibility Assessments 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Safety Assessments 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
 
 
 
 
X 
 
X 
 
Lab: LFT tests only (ALT, 
AST, BILI, GGT) 
 
X 
X 
X 
 
X 
 
 
Pregnancy testingb 
 
 
 
X 
X 
X 
X 
 
Urine drug test 
 
 
 
X 
X 
X 
X 
 
Physical Exam 
 
 
 
 
X 
 
X 
 
Physical Measurements 
 
 
 
X 
X 
X 
X 
 
Vital Signs 
X 
 
 
X 
X 
X 
X 
X 
12-Lead ECG 
 
 
 
X 
X 
X 
X 
 
Concomitant Medication 
Review 
X 
 
 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking 
Scale (STS) 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Outcome 
Assessments 
 
 
 
 
 
 
 
 
Yale-Brown Obsessive 
Compulsive Scale (Y-
BOCS) 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 47 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Clinical Global Impressions-
Severity Scale (CGI-S) 
 
 
 
X 
X 
X 
X 
 
Sheehan Disability Scale 
(SDS)c 
 
 
 
X 
X 
X 
X 
 
Clinical Drug Supply 
 
 
 
 
 
 
 
 
Re-enter subject in IWRS 
X 
 
 
 
 
 
 
 
Dispense Study Drug 
X 
 
 
X 
X 
X 
Xd 
 
Drug Accountability 
 
X 
X 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the additional expanded extension phase. 
aAbbreviated Baseline Visit is needed for returning subjects who completed dosing in the Additional Expanded 
Extension Phase < 4 weeks prior to returning to the study and entering the Additional Expanded Extension Phase.  
bIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Additional Expanded Extension Phase. *Note: A test 
will be sent home at Week 12, 24 and at Week 36 and should be performed once between each visit. 
c If a subject checks the “not working” box for the Work/School item on the SDS, you MUST 
check compliance to this instruction, before the visit ends. 
d Only subjects continuing in the Additional Expanded Extension Phase for an additional 48 weeks of Open-Label 
treatment will be dispensed IP at this visit.  
 
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 48 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Table 7: 
Schedule of Assessments and Events – Additional Expanded Extension Phase 
(all continuing subjects) 
Visit 
Add’l Exp 
Ext 
Wk 
60/108/156 
Add’l Exp 
Ext 
Wk 
72/120/168 
Add’l Exp 
Ext         
Wk 
84/132/180 
Add’l Exp 
Ext 
Wk 
96/144/192 
or early 
term 
Wk2 
Post last 
dose 
Safety Assessments 
 
 
 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
X 
Laboratory Assessments 
 
X 
 
X 
 
Labs: LFT tests only: (ALT, AST, BILI, GGT) 
X 
 
X 
 
 
Pregnancy testinga 
X 
X 
X 
X 
 
Urine drug test 
X 
X 
X 
X 
 
Physical Exam 
 
X 
 
X 
 
Physical Measurements 
 
X 
 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
X 
 
Concomitant Medication Review 
X 
X 
X 
X 
X 
Sheehan Suicidality Tracking Scale (STS) 
X 
X 
X 
X 
X 
Clinical Outcome Assessments 
 
 
 
 
 
Yale-Brown Obsessive Compulsive Scale (Y-
BOCS) 
X 
X 
X 
X 
 
Clinical Global Impressions-Severity Scale 
(CGI-S) 
X 
X 
X 
X 
 
Sheehan Disability Scale (SDS)b 
X 
X 
X 
X 
 
Clinical Drug Supply 
 
 
 
 
 
Dispense Study Drug 
X 
X 
X 
 
 
Drug Accountability 
X 
X 
X 
X 
 
Visit window is +/- 7 days during the additional expanded extension phase.  
aIn addition to urine pregnancy tests conducted at each study visit, subjects will be provided with urine pregnancy 
tests to take in between every 3-month office visit during the Additional Expanded Extension Phase. *Note: test will 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 4 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
be s e nt h o me at Wee k 6 0/ 1 0 8 / 1 5 6, Wee k 7 2/ 1 2 0 / 1 6 8  a n d at Wee k 8 4/ 1 3 2 / 1 8 0 a n d s h o ul d be perf or me d o nce 
bet wee n eac h visit.  
b If a s u bject c hec ks t he “ n ot w or ki n g” b o x f or t he W or k/ Sc h o ol ite m o n t he S D S, y o u M U S T 
c hec k c o m plia nce t o t his i nstr ucti o n, bef ore t he visit e n ds.  
 
4. 3. 1  
S cr e e ni n g P h a s e  
T he Scree ni n g P hase will r a n ge fr o m a mi ni m u m of 2 da ys t o a ma xi m u m of 4 2 . T he p ur p ose of 
t he Scree ni n g Visit is t o e ns ure t hat t he a p pr o priat e p atie nts are e ntere d i nt o t he trial. Scree ni n g 
ca n be as s h ort as 2 da ys as l o n g as t he s u bject has b ee n o n at least 8 wee ks of t h eir c urr e nt S O C 
O C D t hera p y at a n a de q uat e d ose at Scr ee ni n g a n d at least 1 0 wee ks of t h eir c urre nt S O C O C D 
t hera p y ( S S RI, cl o mi pra mi ne , ve nlafa xi n e or des ve nl afa xi ne) at a n a d e q uat e d ose b y t he b as eli n e 
visit .  T he i n vesti g at or will det er mi n e t hat t he patie nt meets eli gi bilit y criteri a a n d will c oll ect 
de m o gra p hi c a n d m e dical dat a prese nti n g a f ull c har acterizati o n of t he p ati e nt.  All att e m pts 
s h o ul d be ma de t o o btai n me dical a n d p har m ac y re c or ds t o c o nfir m t h e s u bject’s me dic al a n d 
me dic ati o n treat me nt hist or y. It is esti m ate d a p pr o xi matel y 3 7 0 s u bjects will e nter t h e scree ni n g 
p hase of t he  tri al. 
T h e S A F E R i nt er vi e w will b e c o n d u ct e d r e m ot el y wit h t h e s u bj e ct b y a C R O s h ortl y aft er 
t h e s cr e e ni n g visit.  A S A F E R p ass is n e c ess ar y f or t h e s u bj e ct f or r a n d o mi z ati o n.  
Please refer t o t he Sc he d ule of Assess me nts/ Ti me & E ve nts f or det ails o n Scre e ni n g Pr oce d ures.   
4. 3. 2  
R a n d o mi z ati o n P h a s e  
S u bjects w h o are deter mi ne d t o be eli gi ble f or t he st u d y will e nt er t he R a n d o mi zati o n P hase. 
S u bjects will r ecei ve tr oril uz ol e (2 0 0 m g Q D)  or pla ce b o ( Q D) (i n a 1: 1 rati o)  i n a d diti o n t o t heir 
S O C  me dicati o n . S u bjects will re cei v e 1 4 0 m g  or pla ce b o f or t he first f o ur ( 4) w ee ks a n d will 
t he n be i n crease d t o 2 0 0 m g or pla ce b o f or t h e d urati o n of t he st u d y.  D o w n titrati o n t o 1 4 0 m g 
will o nl y be all o we d t o a d dress  t ol era bilit y iss ues 
D osi n g will c o nti n u e f or 1 2 wee ks. S u bjects will ret ur n t o t he cli ni c t w o wee ks after 
disc o nti n ui n g st u d y me di cati o n f or a f oll o w -u p safet y visit  ( u nless t he y are c o nti n ui n g i n t he 
E xte nsi o n P hase) . T ele p h o n e calls will be ma de t o t h e s u bject at t h e wee k  2 a n d 6  ti me p oi nts 
d uri n g t his p hase.  T h e p ur p ose of t he tele p h o n e cal l is t o c hec k o n t he s u bje ct’s s y m pt o ms, a n y 
ne w c o nc o mita nt me di cati o ns  a n d t he p ossi bilit y of a d verse e ve nts.  
S u bjects c o m pleti n g t he R a n d o mi zati o n P hase will b e offere d a p pr o xi mat el y 9 6 wee ks of o pe n -
la bel treat me nt as l o n g as t he PI belie v es o pe n-la b el treat m e nt offers a n a cce pta bl e ris k-be nefit 
pr ofile.   
•  S u bjects s h o ul d ta k e t heir me dicati o n i n t he m or ni n gs.  I f t olera bilit y iss ues arise please r efer 
t o Secti o n  9. 2. 5 . 
Please refer t o t he Sc he d ule of Assess me nts/ Ti me & E ve nts f or det ails o n pr oc e d ures d uri n g t he 
Ra n d o miz ati o n P hase. T here is a visit wi n d o w of +/ - 2 da y visit wi n d o w d uri n g t h e 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Ra n d o miz ati o n P hase of t he st u d y. It is esti m ate d t hat a p pr o xi m atel y 2 2 6  s u bjects will e nter t his 
p hase of t he trial.  
E ver y eff ort s h o ul d b e ma de t o c o n d uct t he Wee k 1 2 visit a n d m ai nt ai n t h e +/ - 2 da y wi n d o w. 
H o we ver, d ue t o c o ncer ns relat e d t o t h e C O VI D -1 9 pa n de mi c, t he Wee k 1 2 visit wi n d o w ma y be 
m o difie d b e y o n d t he +/ - 2 da y wi n d o w, i n or der t o mi ni mi ze a n y p ote ntial ris ks t o st u d y 
partici pa nt saf et y a n d t o c o m pl y w it h g o ver n m e ntal a n d l ocal i nstit uti o n al g ui d a nce (e. g., st u d y 
site has a p olic y t h at a cli nical r esearc h visit m ust b e dela ye d)  n ote t h e f oll o wi n g g ui da nce . 
U n der t hese cir c u msta nc es, t he visit wi n d o w ma y be e xte n de d ( u p t o a m a xi m u m treat me nt 
d urati o n of  1 8 wee ks), b ut e ver y atte m pt s h o ul d be ma de t o c o n d uct t he visit as cl ose t o t he date 
t he visit is d ue as p ossi ble. If t h e visit wi n d o w is m o difie d, a n d t he i n v esti gat or deter mi nes t h at a 
re m ote visit offers a n acce pta bl e ris k-be nefit a p pr o ac h a n d is a p pr o priate f or a partic ular s u bje ct, 
partici pa nts s h o ul d be e val uate d re m otel y (e. g., vi a p h o ne) at t h e ti me of t h e sc he d ule d Wee k 1 2 
visit t o perf or m a n d d oc u me nt a p pr o priat e safet y assess me nts. If t he re m ote visit re q uires 
la b orat or y testi n g, l ocal la bs m ust b e a ble t o be o bt ai ne d a n d re vi e we d b y t he site.  St u d y 
me dic ati o n ma y be se nt t o t h e parti ci pa nt via trac k e d a n d certifie d c o urier. F or a n y s uc h c ases, 
t he i n vesti gat or s h o ul d disc uss t he s pecific cir c u msta nces of eac h c ase wit h t h e s p o ns or me dic al 
m o ni t or. 
S p o ns or Me dic al M o nit or  
 
Cell: 
 
 
 
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 51 of 97 
 
Draft Version 10; 13 Oct 2022 
 
4.3.3 
Extension Phase  
Subjects will have visits in the Extension Phase every four weeks through Week 12 and then 
every 12 weeks thereafter up to Week 48. All subjects will undergo a termination visit two 
weeks after the last dose of study drug. Telephone calls will be made to the subject at the week 2 
and 6 time points during this phase.  The purpose of the telephone call is to check on the 
subject’s symptoms, any new concomitant medications and the possibility of adverse events. 
Subjects entering the Extension phase will continue on the same dose that was taken at the end of 
the Randomization phase.  Subjects receiving placebo in the randomization phase will be 
switched in a blinded manner to 140mg for the first 4 weeks, and will then be increased to 
200mg (at the Week 4 visit). Down titration will only be allowed to address tolerability issues. 
All visits starting at week 4 of the Extension Phase will be open-label.  Subjects who enter the 
Extension Phase on 140 mg due to tolerability issues can be rechallenged to increase to 200 mg 
beginning at Extension Week 4 at PI discretion. If a subject has to delay the Randomization 
Phase Week 12 visit due to concerns about COVID-19, the site should contact the Sponsor 
immediately upon learning about the cancelation so that the Sponsor can provide instruction on 
providing study drug. Subjects will not be allowed to transition to the Extension Phase until they 
have an in-person Week 12 visit.  
Please refer to the Schedule of Assessments/Time & Events for details on procedures during the 
Extension Phase. There is a visit window of +/- 7 days during the Extension Phase of the study.  
4.3.4 
Expanded Extension Phase (if applicable) 
Subjects who complete the initial 48 week Extension Phase and are continuing directly into the 
Expanded Extension Phase with no dose interruption will have visits every 12 weeks until Week 
96 of the Expanded Extension Phase. Subjects who previously completed the initial 48 week 
Extension Phase and who have left the study will have the opportunity to re-enter the study 
provided it has not been more than 3 months since completing the study. Returning subjects who 
have been off study medication for less than 4 weeks, will have an abbreviated Baseline visit 
before re-entering the study. Those who have been off study medication for 4 weeks or more will 
undergo a full Baseline Visit. In addition, for returning subjects, safety laboratory assessments 
will be performed 4 and 8 weeks after re-starting study medication. Thereafter, study visits in the 
Expanded Extension Phase will be every 12 weeks until Week 48. Please refer to the Schedule of 
Assessments/Time & Events for details on procedures during the Expanded Extension Phase. 
There is a visit window of +/- 7 days during this phase of the study. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 2  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
4. 3. 5  
A d diti o n al E x p a n d e d E xt e n si o n P h a s e (if a p pli c a bl e)  
S u bjects w h o c o m pl ete t he 4 8 wee k E x p a n de d E xte nsi o n P hase a n d are c o nti n ui n g directl y i nt o 
t he A d diti o n al  E x p a n de d E xte nsi o n P hase wit h n o d ose i nterr u pti o n will h a ve t h eir first visit 1 2 
wee ks after t h e 4 8 t h wee k of t he E x pa n de d E xte nsi o n ( E E We e k 9 6 or E E W ee k 4 8 as i d e ntifie d 
i n Pr ot oc ol versi o n 0 8). T here after, s u bje cts will u n d er g o visits e ver y 1 2 we e ks u ntil Wee k 
9 6/ 1 4 4 / 1 9 2 of t he A d diti o nal E x pa n d e d E xt e nsi o n P hase . S u bjects w h o pre vi o usl y c o m pl ete d t he 
E x pa n de d E xte nsi o n W ee k 4 8/ 9 6 a n d w h o ha v e left t he st u d y will ha v e t he o p p ort u nit y t o re -
e nter t h e st u d y a n d rec ei ve a n a d diti o nal 4 8 wee ks of o pe n la bel tre at me nt pr o vi de d it has n ot 
bee n m ore t ha n 4  wee ks  si nce c o m pl eti n g t he st u d y. Ret ur ni n g s u bje cts will h a ve a n a b bre viate d 
Baseli ne visit bef or e re -e nt eri n g t h e st u d y. I n a d diti o n, f or ret ur ni n g s u bje cts, safet y la b orat or y 
assess me nts will be perf or me d 4 a n d 8 wee ks after re -starti n g st u d y m e dic ati o n. T hereafter, 
st u d y visits i n t he A d diti o nal E x pa n d e d E xt e nsi o n P hase will be e ver y 1 2 wee ks u ntil We e k 9 6 . 
Please refer t o t he Sc he d ule of Assess me nts/ Ti me & E ve nts f or det ails o n pr oc e d ures d uri n g t he 
A d diti o nal E x pa n de d E xte nsi o n P hase. T here is a visit wi n d o w of +/ - 7 da ys d uri n g t his p hase of 
t he st u d y.  
All s u bjects will u n der g o a t er mi nati o n visit t w o wee ks after t he last d ose of st u d y dr u g.  
4. 4  
P o st St u d y A c c e s s t o T h er a p y (if a p pli c a bl e)  
T here is a n e xte nsi o n p h ase , a n e x pa n d e d e xt e nsi o n p hase  a n d a n a d diti o n al e x pa n d e d e xt e nsi o n 
p hase  of t his tri al f or u p t o 1 9 2  we e ks of o pe n -la bel treat m en t as descri be d i n Secti o n s 4. 3. 3 , 
4. 3. 4  a n d 4. 3. 5 . N o ot her st u d y dr u g ac cess is a vail a ble aft er t he e xte nsi o n.  
5  P O P U L A TI O N  
5. 1  
N u m b er of S u bj e ct s  
A p pr o xi matel y 2 2 6  s u bjects are e x pe cte d t o be ra n d o mize d i n t his st u d y.  
5. 2  
I n cl u si o n Crit eria  
5. 2. 1  
Inf or m e d C o n s e nt  
a. S u bjects ( or le g all y acce pta bl e re prese ntati ve as re q uire d b y t he  I R B/I E C) m ust 
pr o vi de a writte n si g ne d i nf or me d c o nse nt f or m/f or ms (I R B/ E C s pecific) pri or t o t he 
initi ati o n of a n y pr ot oc ol re q uire d  pr o ce d ures . 
5. 2. 2  
A g e a n d  S e x  
a. Male a n d fe mal e o ut patie nt s u bj ects bet wee n t h e a ges of 1 8 - 6 5 , i ncl usi ve. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 3  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
5. 2. 3  
T ar g et P o p ul ati o n  
a. Pri mar y dia g n osis of o bsessi ve -c o m p ulsi ve dis or der ( O C D) as per Dia g n ostic a n d 
Statisti cal Ma n u al of Me nt al Dis or ders, Fift h E diti o n  as c o nfir me d b y t he MI NI  at 
Scree ni n g;  T he d urati o n of t he s u bj ect’s ill ness m ust be ≥ 1 year;  
b.  S u bjects m ust be c urre ntl y e x peri e nci n g n o n -r es p o nse or i na de q u ate res p o nse t o 
t heir c urr e nt Sta n d ar d of Care ( S O C)  me di cati o n de fi ne d as: 
1.  S u bjects Y -B O C S t otal sc ore m ust be ≥ 1 9 at Scre e ni n g a n d Baseli ne, 
reflecti n g m o d erate or se v ere O C D s y m pt o ms. 
2.  S u bjects m ust c urr e ntl y b e o n a sele cti v e ser ot o ni n r e u pta ke i n hi bit or ( S S RI ) 
or cl o mi pr a mi n e , ve nl afa xi ne or d es ve nlaf a xi ne m o n ot hera p y tr eat me nt f or a n 
a de q uat e d urati o n  a n d at a n a de q u ate d ose  d efi ne d  as: 
a. A de q uate D urati o n:  At l east 8 wee ks at scr ee ni n g a n d 1 0 wee ks of S S RI , 
cl o mi pr a mi n e, ve nl afa xi ne  or d es ve nlaf a xi ne at Baseli ne. 
b.  A de q u ate D ose: Defi ne d b y t he U S PI la beli n g . Refer t o ta bl e bel o w : 
 
Ge neric  
Bra n d  
Class  
D os e R a n ge 3 
Cit al o pr a m 1, 2 
Cele xa  
S S RI  
2 0 -4 0 m g  
Es cit al o pr a m 2 
Le xa pr o  
S S RI  
1 0 -2 0 m g  
Fl u o xeti ne  
Pr ozac  
S S RI  
2 0 -6 0 m g  
Fl u v o x a mi ne  
L u v o x  
S S RI  
1 0 0 -3 0 0 m g  
P ar o xeti ne  
Pa xil  
S S RI  
4 0 -6 0 m g  
Sertr ali ne  
Z ol oft  
S S RI  
5 0 -2 0 0 m g  
Cl o mi pr a mi ne  
A nafra nil  
T C A  
1 0 0 -2 5 0 m g  
Ve nl af a xi ne 2 
Effe x or X R  
S N RI  
7 5 -2 2 5 m g  
Des ve nl af a xi ne 2 
Pristi q  
S N RI  
5 0 m g  
1D os es a b o ve 4 0 m g/ da y  
C ital o pra m are n ot rec o m me n de d d ue t o t he ris k of Q T pr ol o n gati o n. 2 0 m g/ da y of cital o pra m is t he 
ma xi m u m rec o m me n de d d os e f or patie nts w h o are greater t ha n 6 0 years of a ge, s u bjects wit h he patic 
i m pair me nt, a n d f or C Y P 2 1 9 p o or meta b olizers or t h os e s u bjects ta ki n g ci meti di ne or a n ot her C Y P 2 C 1 9 
i n hi bit or.  
2Cital o pra m, es cital o pra m , ve nlafa xi ne, a n d des ve nlafa xi ne are n ot F D A a p pr o ve d f or O C D.  A P A 
g ui deli nes f or O C D i n cl u de t he use of cital o pra m, es cital o pra m a n d ve nlafa xi ne . D os es liste d are f or maj or 
de pressi ve dis or d er.  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 4  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
3 Hi g her d os es of S S RI (e xce pt f or cital o pra m), cl o mi pra mi ne, ve nlafa xi ne  or  des ve nlafa xi ne are all o we d 
pr o vi de d t he d os e has bee n sta ble, is well t olerate d a n d t here are n o s afet y c o ncer ns. T his ass ess me nt 
s h o ul d be d oc u me nte d i n t he s o urce d oc u me nt. 
c. S u bjects m ust be o n st a ble d oses of ot h er ps yc h otr o pic me dicati o n ( wit h 
e xcl usi o ns s pecifie d bel o w) f or at le ast 1 2  wee ks pri or t o scree ni n g;  
d.  C GI -S sc ore of ≥ 4 at scree ni n g a n d b aseli ne;  
e. Deter mi n e d b y t he i n vesti g at or t o be me di call y sta bl e at 
b aseli ne/ra n d o mizati o n as assesse d b y me di cal hist or y, p h ysical 
e xa mi n ati o n, la b orat or y tes t res ults, a n d el ectr o car di o gra m testi n g. 
S u bjects m ust be p h ysi call y a bl e a n d e x pe cte d t o c o m plet e t he trial  as 
desi g ne d;  
f. Mi ni m u m of 6 ye ars of e d ucati o n  or e q ui v ale nt  a n d s ufficie ntl y fl u e nt i n 
E n glis h  t o c o m plete ne cessar y scales a n d u n d ersta n d c o nse nt f or ms; 
g.  S u bjects m ust ha v e a de q u ate he ari n g, visi o n, a n d la n g ua ge s kills t o 
perf or m ne ur o ps yc hi atric testi n g a n d i nt er vie ws as s pecifi e d i n t h e 
pr ot oc ol;  
h.  S u bjects m ust be a ble t o u n dersta n d a n d a gree t o c o m pl y wit h t h e 
prescri be d d osa ge re gi me ns a n d pr o ce d ures; r e p ort f or re g ularl y sc h e d ule d 
office visits; a n d relia bl y c o m m u nicate wit h st u d y p ers o n nel a b o ut  a d verse 
e ve nts a n d c o n c o mita nt  me dicati o ns;  
i. It is re q uire d t hat all w o m e n of c hil d -b eari n g p ote nti a l (W O C B P ) w h o are 
se x uall y a cti v e a gree t o use t w o met h o ds of c o ntra ce pti o n f or t he d ur ati o n 
of t he st u d y (i.e. b e gi n ni n g 3 0 d a ys pri or t o baseli ne a n d e xte n di n g t o 3 0 
da ys after t he last d ose of st u d y dr u g). T he t w o met h o ds s h o ul d i ncl u de: 
1)  o ne barrier met h o d (e. g. dia p hra g m wit h s per mici d e, 
c o n d o m wit h s per mici d al gel, i ntr a uteri n e de vi ces, 
cer vic al ca p) ; 
2)  a n d o ne ot her met h o d. T he ot her met h o d c o ul d i n cl u de 
h or m o nal  c o ntrac e pti ves (e. g. or al c o ntrac e pti v es, 
i njecta bl e c o ntra ce pti ves or c o ntr ace pti ve i m pl a nt) or 
a n ot her barrier met h o d ( Secti o n  5. 5 ); 
j. W o me n of c hil d be ari n g p ote ntial m ust ha v e a ne g ati ve ser u m pre g na n c y 
test at scr ee ni n g a n d a ne gati ve uri ne pre g n a nc y t est pri or t o d osi n g  at 
Baseli ne ;  
k.  It is re q uire d t hat me n w h o are se x uall y a cti v e wit h W O C B P a gree t o use 
t w o met h o ds of c o ntr ace pti o n f or t he d ur ati o n of t he st u d y ( be gi n ni n g at 
first treat me nt a n d e xte n di n g t o 90 d a ys after t he l ast d ose of st u d y dr u g).  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 5  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
5. 3  
E x cl u si o n Crit eri a  
5. 3. 1  
T ar g et Di s e a s e  E x c e pti o n s  
a. S u bjects s h o ul d be e x cl u de d wit h a hist or y of  m ore t ha n t w o ( 2) pre vi o us faile d 
treat me nt trials of S S RIs, cl o mi pra mi ne, ve nl afa xi n e, or des ve nlafa xi ne, ( n ot 
i ncl u di n g t he c urr e nt S S RI trial) gi ve n f or a n a de q uate d urati o n at a n a de q uate 
d ose as defi ne d b y t h e foll o wi n g criteria t a ke n fr o m t he M G H-T R Q -O C D as:  
i. Trea tme nt f ail ure / n o n -res p o nse:  As per t he M G H-T R Q -O C D, t here 
has bee n mi ni mal or n o me a ni n gf ul cli ni cal b e nefit as percei ve d b y t he 
patie nt des pit e a n a de q u ate d ose a n d d urati o n of tre at me nt;  
ii. A de q uate d urati o n: At least 1 0 wee ks of tr eat me nt wit h S S RI, 
cl o mi pr a mi n e, ve nl afa xi ne or d es ve nlaf a xi ne  
iii. A de q uate d ose: Defi ne d b y t he U S PI la beli n g.  Ref er t o t he t a ble b el o w:  
 
Ge neric  
Bra n d  
Class  
D os e R a n ge 3 
Cit al o pr a m 1 
C ele xa  
S S RI  
2 0 -4 0 m g  
Es cit al o pr a m 1, 2 
Le xa pr o  
S S RI  
1 0 -2 0 m g  
Fl u o xeti ne  
Pr ozac  
S S RI  
2 0 -6 0 m g  
Fl u v o x a mi ne  
L u v o x  
S S RI  
1 0 0 -3 0 0 m g  
P ar o xeti ne  
Pa xil  
S S RI  
4 0 -6 0 m g  
Sertr ali ne  
Z ol oft  
S S RI  
5 0 -2 0 0 m g  
Cl o mi pr a mi ne  
A nafra nil  
T C A  
1 0 0 -2 5 0 m g  
Ve nl af a xi ne  
Effe x or X R  
S N RI  
7 5 -2 2 5 m g  
Des ve nl af a xi ne  
Pristi q  
S N RI  
5 0 m g  
1D os es a b o ve 4 0 m g/ da y of cital o pra m are n ot rec o m me n de d d ue t o t he ris k of Q T pr ol o n gati o n.  2 0 
m g/ da y of  
C ital o pra m is t he ma xi m u m rec o m me n de d d os e f or patie nts w h o are greater t ha n 6 0 years of a ge, s u bjects 
wit h he patic i m pair me nt, a n d f or C Y P 2 1 9 p o or meta b olizers or t h os e s u bjects ta ki n g ci me ti di ne or a n ot her 
C Y P 2 C 1 9 i n hi bit or.  
2Cital o pra m, es cital o pra m, ve nlafa xi ne, a n d des ve nlafa xi ne are n ot F D A a p pr o ve d f or O C D.  A P A 
g ui deli nes f or O C D i ncl u de t he use of cital o pra m, es cital o pra m  a n d ve nlafa xi ne. D os es liste d are f or maj or 
de pressi ve dis or d er.  
3 Hi g her d os es of S S RI (e xce pt f or cital o pra m), cl o mi pra mi ne, ve nlafa xi ne  or  des ve nlafa xi n e  are all o we d 
pr o vi de d t he d os e has bee n sta ble, is well t olerate d a n d t here are n o s afet y c o ncer ns. T his ass ess me nt 
s h o ul d be d oc u me nte d i n t he s o urce d oc u me nt. 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 6  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
b.  S u bjects s h o ul d be e x cl u de d at scree ni n g or baseli ne if a n y me dical or 
ps yc hiatri c c o n diti o n ot h er t ha n O C D, as s pecifi e d i n t he i ncl usi o n criteri a, 
c o ul d pre d o mi na ntl y e x pl ai n or c o ntri b ute si g nific a ntl y t o t h e s u bjects’ 
s y m pt o ms or t hat c o ul d c o nf o u n d assess me nt of O C D s y m pt o ms; 
c. M M S E sc ore of < 2 4  at S cree ni n g;  
d.  C urre nt or pri or hist or y , p er D S M-5 criteria,  of bi p ol ar I or II dis or der, 
sc hiz o p hre ni a or ot her ps yc h otic dis or ders, sc hi z oaff ecti v e dis or der, a utis m or 
a utisti c s pectr u m dis or ders, b or derli n e pers o nalit y dis or der , a ntis oci al 
pers o nalit y dis or der, b o d y d ys m or p hic dis or der, h oar di n g dis or der  (s y m pt o ms 
of h oar di n g dis or der as part of t he O C D dia g n osis ar e all o we d, b ut a pri mar y 
dia g n osis of h oar di n g dis or der is e xcl u d e d); a c urr e nt dia g n osis of T o urette’s 
dis or der is als o e xcl u de d ; 
e. A n y eati n g dis or der wit hi n t h e last 1 2 m o nt hs;  
f. Pri mar y acti ve maj or de pr essi ve e pis o de or pri mar y acti v e a n xi et y dis or der 
wit hi n t he p ast 6 m o nt hs. N ote: S u bjects o n a sta bl e mai nt e na nc e d ose of a n o n -
tric yclic, n o n-m o n oa mi ne o xi dase i n hi bit or ( M A OI) a nti d e pr essa nt me dicati o n  
ma y be eli gi ble if t he s u bject has bee n treate d wit h a sta ble d ose f or at le ast 3 
m o nt hs pri or t o ra n d o miz ati o n a n d n o d ose c ha n ges are e x pe cte d t hr o u g h o ut 
t he ra n d o mizati o n p hase of t h e st u d y;  
g.  Ac ute s uici d alit y or s uici d e atte m pt or self i nj uri o us be ha vi or i n t he l ast 1 2 
m o nt hs.  
h.  Sc ore of > 0 o n t he S hee h a n S uici d alit y Trac ki n g Scale f or t he p eri o d of 6  
m o nt hs  pri or t o scre e ni n g  a n d at b aseli ne;  
i. Br o w n Assess me nt of Beli efs ( B A B S)  sc ore > 1 7  at scree ni n g a n d b aseli ne;  
j. Patie nts w h o ma y h a ve re cei ve d a n o n -bi ol o gical i n v esti gati o nal a ge nt i n a n y 
cli ni cal trial wit hi n 3 0 d a ys or a bi ol o gical a ge nt wit hi n 9 0 da ys pri or t o 
scree ni n g; 
k.  Hist or y of ps yc h os ur ger y, Dee p Brai n Sti m ulati o n ( D B S) or Electr oc o n v ulsi ve 
T hera p y ( E C T) . 
5. 3. 2  
M e di c al Hi st or y E x cl u si o n s  
a. Hist or y of s u bsta nce use dis or der  ( dr u g or al c o h ol) i n t he last 1 2 m o nt hs, wit h t h e 
e xce pti o n of t o ba cc o, as defi n e d b y D S M-5  criteria;  
b.  P ositi ve uri ne dr u g scr ee ni n g f or  c a n na bis  ( b ot h me dical a n d recre ati o n al use of 
ca n n abis ar e pr o hi bite d ; s u bj e cts will  b e  e x p e ct e d  t o r efr ai n fr o m us e  d uri n g  
t h e p eri o d  of  t h e st u d y), a m p het a mi n es (i ncl u di n g M D M A/ecstas y), c ocai ne, 
bar bit urate, P C P , a n d/ or o pi ates  at scree ni n g or b aseli ne ; 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
c. Pri or or c urre nt ge n eral m e dic al c o n diti o n t hat ma y c o nf o u n d a bilit y t o i nter pret 
safet y a n d efficac y r es ults as det er mi n e d b y t he I n v esti gat or ; 
d.  Cli nic al hist or y of str o k e , seiz ur e dis or der, tra u matic brai n i nj ur y wit h o n g oi n g  
se q uelae.  
e. B o d y mass i n de x > 4 0 k g/ m 2 ; 
f. Acti ve li ver dise ase or a hist or y of he p ati c i nt olera n c e t o me dicati o ns t hat, i n t h e 
i n vesti gat or’s j u d g me nt, is me dicall y si g nifica nt;  
g.  Vita mi n B 1 2 or f olat e defi cie nc y N ot e: S u bje cts wit h a B 1 2 deficie nc y ca n 
partici pat e i n t h e st u d y if t h e y are o n sta bl e Vit a mi n B 1 2 re plac e me nt f or at l east 
3 m o nt hs pri or t o ra n d o miz ati o n a n d t heir B 1 2 le vels are wit hi n n or mal li mits 
pri or t o ra n d o mizati o n;  
h.  He mat ol o gic or s oli d mali g na nc y dia g n osis wit hi n 5 years pri or t o scree ni n g. 
N ote: S u bjects wit h a hist or y of l ocalize d s ki n ca nc er, basal cell or s q ua m o us 
cell carci n o ma, m a y be e nr olle d i n t he st u d y as l o n g as t he y are ca ncer fr ee pri or 
t o ra n d o mi zati o n. S u bjects wit h ot her l ocalize d ca nc ers ( wit h o ut metastatic 
s prea d) w h o ha ve pre vi o usl y c o m plete d t h eir c o urse of treat me nt m ore t ha n 5 
years pri or t o scree ni n g, are n ot c urre ntl y re cei vi n g treat m e nt a n d h a ve bee n i n 
re missi o n ma y b e e nr olle d o nl y if, i n t he o pi ni o n of t he i n vesti g at or, t h ere is n o 
e x pect ati o n f or re c urre nc e or f urt her ca ncer treat me nt d uri n g t he st u d y p eri o d. 
A nti h or m o nal t hera p y ( e. g., ta m o xife n) is all o we d if t he s u bject's c a ncer is i n 
re missi o n a n d t h e s u bject is o n sta bl e mai nte na n ce t h era p y t o re d u ce t heir ris k of 
rec urre nce;  
i. A n y u nsta ble car di o vasc ular (i ncl u d es u nc o ntr olle d h y perte nsi o n), p ul m o nar y, 
gastr oi ntesti nal, or h e patic disease 3 0 d a ys pri or t o s cree ni n g;  
j. E n d -sta ge c ar di o vasc ul ar disease ( e. g., C o n gesti v e Heart Fail ure Ne w Y o r k 
Heart Ass ociati o n/ C H F N Y H A Class III or I V or u nsta ble a n gi na);  
k.  P ositi ve s y p hilis ser ol o g y i ncl u di n g ra pi d plas ma r ea gi n [ R P R] test a n d p ositi ve 
c o nfir mat or y testi n g;  
l. Hist or y of c hr o nic p ul m o nar y dise ase or c hr o nic p ul m o nar y s y m pt o ms ; 
m.  I m m u n oc o m pr o mise d s u bje cts. N ote: S u bj ects t a ki n g a s yste mic 
i m m u n os u p pressi ve a g e nt m a y be ra n d o mize d o nl y if t he y are o n a sta ble 
d ose, ha ve n o cli nic all y rele va nt i m m u n os u p pressi o n, a n d ha ve a w hite bl o o d 
c o u nt ( W B C) wit hi n n or mal  li mits; 
n.  Hist or y of me dic all y si g nific a nt  gastr oi ntesti n al ( GI) ill nesses  i ncl u di n g: 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 8  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
i. A c urre nt dia g n osis of a cti ve, p e pti c ulc erati o n or  gastr oi ntesti n al 
blee di n g wit hi n t h e last 6 m o nt hs a n d/ or c hr o nic i nfl a m mat or y b o wel 
disease at  scree ni n g; 
ii. A hist or y of a n y gastr oi nt esti nal s ur ger y t hat i m pa ct s t he a bs or pti o n of 
st u d y dr u g;  
iii. C hr o nic or fre q ue nt e pis o des of l o ose  st o ols; 
o.  Hist or y or e vi de nc e of a n y me dical, ne ur ol o gical or ps yc h ol o gical c o n diti o n t h at 
w o ul d e x p ose t he s u bje ct t o a n u n d ue ris k of a si g nifica nt a d verse e ve nt or 
i nterfer e wit h assessme nts of safet y a n d effi cac y  d uri n g t he c o urse of t h e tri al as 
deter mi ne d b y t h e cli nical j u d g m e nt of t h e i n vesti gat or . 
p.  W o me n w h o are pre g n a nt or bre astfee di n g.  
5. 3. 3  
P h y si c al a n d L a b or at or y T e st Fi n di n g s  
a. U nc o ntr olle d h y p erte nsi o n at scree ni n g (e. g., re p eat e d diast olic 
meas ure m e nts ≥ 9 6  m m H g);  
b.  Dia g n osis of h y p ot h yr oi dis m b y a scr ee ni n g t h yr oi d sti m ulati n g h or m o n e ( T S H) 
val ue > t h e u p per li mit of n or mal ( U L N) a n d free t h yr o xi ne ( T 4) < t h e l o wer 
li mit of n or mal ( N ote: S u bj ects wit h hist or y of h y p ot h yr oi dis m ma y p arti ci pate 
i n t he st u d y, pr o vi d e d t he y are e ut h yr oi d o n sta bl e t h yr oi d re pla ce m e nt t her a p y 
f or at le ast 3 m o nt hs pri or t o scree ni n g, a n d t her a p y is e x pecte d t o re m ai n sta bl e 
d uri n g t he c o urse of  t h e st u d y; 
c. He patic test a b n or malities at scree ni n g ( ma y b e re pe ate d o ne ti m e f or 
c o nfir mati o n i n scr ee ni n g pri or t o  baseli n e):  
i. As partate A mi n otra nsferase ( A S T), Ala ni n e  
A mi n otra nsferase ( A L T) or G G T > 1. 5 ti mes t he 
u p per li mit of n or m al;  or  
ii. T otal bilir u bi n > 2 ti mes t he u p p er li mit of n or mal ( U L N ; u nless 
s u bject has d oc u me nt e d hist or y of Gil bert’s S y n dr o me i n w hic h case 
s u bject m a y be e nr olle d wit h per missi o n of t h e S p o ns or).  
d.  P -A m ylase or  Li pase v al ues greater t h a n 1. 5 ti mes t h e u p per li mit of 
n or mal at scree ni n g ( U L N) ( ma y be re p eat e d o ne ti m e f o r c o nfir m ati o n i n 
scree ni n g pri or t o baseli ne);  
e. H b A 1 C ≥ 7. 0 %  at scree ni n g; 
f. Pat h ol o gic r e nal fi n di n gs at scre e ni n g as defi ne d b y t he prese nce of  eit her 
of t he f oll o wi n g  criteri a:  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 5 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
i. Esti mate d gl o mer ul ar filtrati o n r ate ( e G F R) a cc 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 dific ati o n of Diet i n Re n al 
Disease ( M D R D) St u d y e q uati o n < 3 0 ml/ mi n/ 1. 7 3 m 2; T he M D R D 
esti mati o n is c alc ulat e d as f oll o ws: e G F R ( m L/ mi n/ 1. 7 3 m 2) = 1 7 5 x 
(sta n dar diz e d Scr)-1. 1 5 4 x ( A ge) -0. 2 0 3 x ( 0. 7 4 2 if fe male) x ( 1. 2 1 2 if 
Blac k). [ Scr: St a n dar di ze d ser u m  creati ni n e];  
ii. Creati ni ne ≥ 2 m g/ d L  
g.  He mat ol o gic a b n or maliti es at  scree ni n g: 
i. He m o gl o bi n < 1 0 g/ d L;  or  
ii. W B C < 3. 0 x 1 0
3/ m m3 ; or  
iii. Platel et c o u nt <  1 0 0, 0 0 0/ m m 3. 
h.  H u ma n I m m u n o defici e nc y Vir us ( HI V) p ositi ve at s cree ni n g (i n d ic ate d b y 
p ositi ve c o nfir mat or y Wester n  Bl ot);  
i. H Bs A g or H C V p ositi ve at  scre e ni n g; 
j. Q Tc F  ( Fri derici a) i nt er val ≥ 4 7 0 msec d uri n g t he  scr ee ni n g or baseli ne  
peri o d or u nc o ntr olle d arr h yt h mi a or fre q ue nt pre m at ure ve ntri c ular 
c o ntracti o n ( P V Cs) ( > 5/ mi n ut e) or M o bitz T y pe II s ec o n d or t hir d d e gree 
atri o ve ntric ular ( A V) bl oc k or left b u n dle br a nc h bl o c k, or ri g ht b u n dl e 
bra nc h bl oc k wit h a Q R S d urati o n ≥ 1 5 0 msec or i n tr a ve ntri c ular 
c o n d ucti o n d efect wit h a Q R S d urati o n ≥ 1 5 0 msec or e vi de nc e of ac ut e  or 
s u b-ac ute m y o car dial i nfar cti o n or  isc he mia or ot her E C G fi n di n gs t hat, i n 
t he i n vesti gat or’s o pi ni o n, w o ul d precl u de partici p ati o n i n t he st u d y. 
5. 3. 4  
Pr o hi bit e d Tr e at m e nt s a n d/ or  T h er a pi e s  
a. Be ha vi oral t her a p y  (c o g niti ve be h a vi oral t her a p y or e x p os ure res p o nse 
pre ve nti o n t hera p y) f or O C D t hat h as bee n i niti ate d wit hi n 3 m o nt hs pri or 
t o scree ni n g  a n d e x pecte d t o c ha n ge d uri n g t he 1 2 -w ee k tre at m e nt peri o d 
( n ote: C ha n ges i n be ha vi oral t hera p y d uri n g t he o pe n la bel p h ase are 
acce pta bl e  after E xte nsi o n ( or E x pa n de d E xte nsi o n) wee k 4 ); 
b.  Pre vi o us treat me nt wit h ril u z ole ; if s u bject is re-e nteri n g t he st u d y i n t he 
E x pa n de d E xte nsi o n P hase, t h e n n o use of ril uz ole wit hi n 1 2 h o urs of 
starti n g tr oril uz ole. 
c. Use of tric yclic a nti de pressa nts a n d m o n o -a mi ne-o xi dase ( M A O) i n hi bit ors are 
pr o hi bite d 3 0 d a ys pri or t o ra n d o mizati o n ( baseli ne visit) a n d d uri n g t he  st u d y 
( wit h t he e x ce pti o n of cl o mi pra mi ne); 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
d.  Us e of a  sti m ul a nt, n e ur ol e pti c  ( a nti ps y c h oti c), mo o d sta bilizer a n d gl ut a m at e  
a g e nt  ( e. g. t o pir a ma t e, l a m otri gi n e, N - a c et yl c yst ei n e,  k et a mi n e,  m e m a nti n e, 
s o di u m v al pr o at e) is pr o hibite d wit hi n  t h e 4  w e e ks  pri or t o s cr e e ni n g  a n d 
d uri n g t h e st u d y ;  
e. T h e us e of a d e p ot n e ur ol e pti c is pr o hi bit e d 6 m o nt hs pri or t o r a n d o mi z ati o n 
( b as eli n e visit); 
f. Us e of v ar e ni cli n e ( C h a nti x) is pr o hi bit e d 3 0 d a ys pri or t o r a n d o mi z ati o n 
( b as eli n e visit) a n d d uri n g t h e ra n d o mi z ati o n p h as e of t h e st u d y;  
g.  C urr e nt  d ail y  a n xi ol yti c  or  b e n z o di a z e pi n e  us e  is pr o hi bit e d  N ot e:  L o w  d os e 
a n xi ol yti c pr e -m e di c ati o ns pri or t o n e c e ss ar y m e di c al di a g n osti c t esti n g pr n 
ar e all o w e d as ar e n o n -b e n z o di a z e pi n e h y p n oti cs  f or slee p if us e d  pr n , a n d 
l o w d os e b e n z o di a z e pi n es ( Ati v a n u p t o 1 m g/ d a y or a p pr o xi m at el y 
e q ui v al e nt  b e n z o di a z e pi n e ) f or sl e e p or a n xi et y if us e d at a st a bl e d os e pr n 
f or at l e ast 3 m o nt hs pri or t o s cr e e ni n g; 
h.  Her bal me dicati o n  a n d her b al s u p ple me nt use wit hi n 3 0 da ys of ra n d o miz ati o n 
a n d d uri n g t he c o urse of t he st u d y is pr o hi bite d ;  
i. Tra nscra ni al Ma g netic Sti m ulati o n ( T M S) is pr o hi bit e d wit hi n t hr ee m o nt hs 
pri or t o scree ni n g a n d d uri n g t he st u d y.  
5. 4  
Pr o hi bit e d C o n c o mit a nt M e di c ati o n  
Pri or use of ril uz ol e is pr o hi bite d  
T he use of t he f oll o wi n g m e dicati o ns is pr o hi bite d 3 0 da ys pri or t o ra n d o mizati o n ( baseli ne visit) 
a n d d uri n g t he E N TI R E st u d y. S u bje cts s h o ul d ha ve n o pla ns t o start t hese m e dic ati o ns d uri n g 
t he st u d y: 
•  Me dical  or recreati o nal marij ua na  
•  Ca n na bi di ol ( C B D) oil  
•  T ric yclic a nti d e pressa nts ( wit h t he e xce pti o n of cl o mi pra mi n e) 
•  M o n o a mi ne-o xi d as e ( M A O) i n hi bit ors  
T h e us e of t h e f oll o wi n g m e di c ati o ns is pr o hi bit e d 4 w e e ks pri or t o s cr e e ni n g  a n d d uri n g t h e 
st u d y: sti m ul a nts, n e ur ol e pti cs,  m o o d sta bilizer a n d gl ut a m at e  a g e nts  ( e. g. t o pir a ma t e, 
l a m otri gi n e, N - a c et yl c yst ei n e,  k et a mi n e,  m e m a nti n e,  s o di u m v al pr o at e) . 
T r oril uz ole s h o ul d b e us e d wit h c a uti o n wit h m e di c ati o ns t h at ar e i n hi bit ors or i n d u c er s of 
t h e C Y P 1 A 2 e n z y m e s yst e m d u e t o t h e p ot e nti al f or dr u g i nt er a cti o ns.  S u bj e cts s h o ul d b e 
m o nit or e d a p pr o pri at e l y w h e n t a ki n g a C Y P 1 A 2 i n hi bit or or i n d u c er .  T h e  f oll o wi n g 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 1  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
m e di c ati o ns  ar e  pr o hi bit e d  at  l e ast 5  h alf -li v es pri or  t o r a n d o mi z ati o n a n d  d uri n g t he st u d y 
(A p p e n di x II, S e cti o n 1 7. 2 ):  
•  Str o n g t o m o d er at e C Y P 1 A 2 i n hi bit ors w hi c h m a y i n cr e as e t h e ris k of ril u z ol e 
ass o ci at e d a d v ers e e v e nts.  
•  Str o n g t o m o d er at e C Y P 1 A 2 i n d u c ers w hi c h m a y r es ult i n d e cr e as e d effi c a c y  
•  H e p at ot o xi c dr u gs ( e. g. all o p uri n ol, m e t h yl d o p a, s ulf as z al zi n e) w hi c h m a y i n cr e as e t h e 
ris k f or h e p at ot o xi cit y 
N ot e: fl u v o x a mi n e (C Y P 1 A 2 i n hi bit or) is all o w e d .  A pri or st u d y i n O C D us e d ril u z ol e as 
a dj u n cti v e tr e at m e nt t o fl u v o x a mi n e  4 .  Or al c o ntr a c e pti v es w hi c h c o nt ai n et hi n yl estr a di ol  
( C Y P 1 A 2 i n hi bit or) ar e als o all o w e d.    
S u bj e cts e nt eri n g t his st u d y m ust h a v e b e e n o n a st a n d ar d of c ar e m e di c ati o n, d efi n e d as a n 
S S RI , cl o mi pr a mi n e , v e nl af a xi n e or d es v e nl af a xi n e, f or t h eir O C D.  T h e y  m ust  h a v e  b e e n  o n  
a  st a bl e t h er a p e uti c d os e  of  t his m e di c ati o n wit h a n i n a d e q u at e r es p o ns e f or at l e ast 8 w e e ks 
at s cr e e ni n g a n d at l e ast 1 0 w e e ks at b as eli n e . N o  c h a n g es  i n t he d ose of t he S S RI , 
cl o mi pra mi ne, ve nlafa xi ne or des ve nlafa xi ne  ar e  all o w e d  t hr o u g h o ut t h e R a n d o mi z ati o n P h as e  
of  t h e st u d y. 
H y p n oti c Us e: N e w us e of h y p n oti cs s h o ul d b e a v oi d e d. F or t h e m a n a g e m e nt of p ersist e nt 
sl e e pi n g diffi c ulti es  or  i ns o m ni a, s u bj e cts m a y  r e c ei v e t h e f oll o wi n g m e di c ati o ns  at  n o  hi g h er 
t h a n t h e i n di c at e d d os es  s u c h as:   
•  Z ol pi d e m  t artr at e ( A m bi e n): u p  t o 1 0  m g  at  b e dti m e  ( H S) as  n e e d e d  ( pr n); 
o  Z ol pi d e m  t artr at e e xt e n d e d -r el e as e ( A m bi e n C R):  u p t o 1 2. 5  m g  at  H S  pr n;  
o  Z al e pl o n ( S o n at a): u p t o 2 0 m g at H S pr n  
o  Es z o pi cl o n e ( L u n est a): u p t o 3 m g at H S pr n.  
L o w d ose  a n xi ol ytic pre-me dic ati o ns pri or t o nec essar y me di cal dia g n osti c testi n g pr n are 
all o we d.  Ati v a n ( u p t o 1 m g/ da y ) or e q ui v ale nt be nz o di aze pi ne f or slee p a n d a n xi et y is all o we d 
if use d pr n at a st a ble d ose f or at le ast 3 m o nt hs pri or t o scree ni n g.  S u bj ects s h o ul d be 
e nc o ura ge d t o a v oi d ta ki n g a b e nz o di aze pi ne t h e m or ni n g of a st u d y visit.  B e nz o di aze pi nes 
s h o ul d n ot be i nitiate d d uri n g t he Ra n d o miz ati o n p hase of t he st u d y. 
T he d ose of t he S O C  s h o ul d n ot be c ha n ge d d uri n g t he Ra n d o mi zati o n P hase of t he trial.  T he 
S O C  d ose ma y be c ha n ge d d uri n g t he E xte nsi o n ( or E x pa n de d E xte nsi o n) P hase if n ee de d b ut n o 
s o o ner t ha n aft er t wel ve we e ks of treat me nt d uri n g t h e E xte nsi o n  ( or E x pa n de d E xte nsi o n)  
p hase.  S u bjects w h o e nt er t he E xte nsi o n  ( or E x p a n d e d E xte nsi o n) P hase o n 1 4 0 m g d ue t o 
t olera bilit y iss ues ca n be re c halle n ge d t o i ncr ease t o 2 0 0 m g be gi n ni n g at E xte nsi o n  ( or 
E x pa n de d E xte nsi o n) W ee k 4 at PI discr eti o n.   

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 2  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Ot her me di cati o ns:  Ot her me dicati o ns n ot e x plicitl y call e d o ut her ei n are all o we d d uri n g t he 
Ra n d o miz ati o n P hase, pr o vi de d t h e y ( 1) ha ve be e n prescri be d f or a s ufficie nt d ur ati o n ( at l east 
3 0 da ys)  t hat t h e i n vesti gat or ca n a de q u atel y assess t olera bilit y a n d dee ms t he m t o be well -
t olerate d; ( 2) d o n ot li mit s u bj ect’s a bilit y t o perf or m ke y rati n g sc ales b y t h e i m pressi o n of t h e 
i n vesti gat or ; a n d, ( 3) t he re gi me n a n d d ose (± 2 5 %) ha ve bee n st a ble f or at le ast 3 0 da ys pri or t o 
scree ni n g a n d are n ot a ntici pat e d t o c h a n ge d uri n g t h e Ra n d o mi zati o n P hase ; ( 4) c o ul d a d versel y 
affect assess me nt of safet y or  effica c y.   
A n y me dicati o n a dj ust me nts or t he i niti ati o n of ne w me dic ati o ns ar e rec o m me n de d t o be 
a d dresse d d uri n g t he E xte nsi o n ( or E x p a n de d E xte nsi o n) P hase, prefera bl y n o s o o ner t ha n aft er  
f o ur w ee ks of treat me nt d uri n g t his p hase s o as n ot t o c o nf o u n d assess me nt of safet y /  
t olera bilit y. 
Me dicati o ns f or t he s h ort t er m tre at m e nt of i nterc urr e nt ill ness are all o we d if ne e de d, pr o vi d e d 
t he y are n ot ot her wise e x cl u de d as n ote d a b o v e. 
A n y ne w me dicati o ns i nitiate d d uri n g t he st u d y  s h o ul d als o be c o nsist e nt wit h t he U S PI f or t he 
sta n dar d of care S S RI a n d ot her c o nc o mit a nt m e dic ati o ns  ta ke n b y t he s u bje ct.   
L oraz e pa m u p t o 1 m g/ da y ( or e q ui vale nt be nz o diaze pi ne) ca n be use d pr n d uri n g t he E xte nsi o n  ( or 
E x pa n de d E xte nsi o n) P hase w he n cli nicall y re q uir e d per i n vesti gat or j u d ge me nt. S u bjects s h o ul d be 
e nc o ur a ge d t o a v oi d ta ki n g t hese me dicati o ns wit hi n 8 h o urs of sc he d ule d effic ac y assess me nts.  
T he ge neric na me ( w here p ossi ble), st art date, e n d d ate a n d d osi n g i nf or mati o n f or a n y 
me dic ati o n ( pr escri pti o n or n o n -prescri pti o n) ta k e n wit hi n 1 m o nt h pri or t o t h e scree ni n g visit 
will be re c or de d i n t he c o nc o mit a nt m e dic ati o n ele ctr o nic case r e p ort f or m.  
I n or der t o e ns ure t h at a p pr o pri ate c o nc o mita nt t her a p y is a d mi nist ere d, it is esse nti al t h at 
s u bjects be i nstr u cte d n ot t o t a ke a n y m e dic ati o n, eit her n o n-prescri pti o n or prescri pti o n t her a p y 
prescri be d b y a n ot her p h ysici a n, wit h o ut pri or c o ns ultati o n wit h t h e i n vesti gat or.  
Patie nts s h o ul d n ot u n d er g o a n y electi ve me dic al pr o ce d ure wit h o ut pri or c o ns ultati o n wit h t he 
I n vesti gat or. A n electi ve pr oc e d ure ( mi n or s ur ger y, de ntal s ur ger y, ort h o pe di c s ur ger y etc …) 
t hat mi g ht re q uire h os pit ali zati o n or a nest hesi a s h o ul d be deferre d u ntil after t h e st u d y w he ne ver 
cli ni call y a p pr o pri ate.  
5. 5  
W o m a n of C hil d b e ari n g P ot e nti al  
W o me n of c hil d be ari n g p ote ntial ( W O C B P) i ncl u d e a n y fe male w h o has e x peri e nce d me nar c he 
a n d w h o has n ot u n der g o ne s uccessf ul s ur gic al sterili zati o n ( h yst erect o m y, bilater al t u b al 
li gati o n, or bil ater al o o p h orect o m y) or is n ot p ost me n o pa usal. P ost-me n o pa us al is defi n e d as: 
•  A me n orr hea greater t h a n or e q ual t o 1 2 c o nse c uti v e m o nt hs wit h o ut a n ot her c a use a n d a 
d oc u me nt e d ser u m f ollicle sti m ulati n g h or m o ne ( F S H) le vel > 3 5 mI U/ m L or;  
•  W o ma n wit h irre g ul ar me nstr ual peri o ds a n d a d oc u me nte d ser u m  f ollicle sti m ulati n g 
h or m o ne ( F S H) le v el > 3 5 mI U/ m L or;  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 3  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
•  N O T E: 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 he a of great er t ha n or e q ual t o o ne  y ear;  
W o ma n o n h or m o n e re pl ace m e nt t h era p y  ( H R T). 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 4  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
T he re q uisite dr u g i nteracti o n st u di es t o det er mi n e t h e i nter acti o n of tr oril uz ole wit h oral 
c o ntrac e pti v es ha ve n ot be e n c o m plet e d  t o date. It is t heref ore n ot p ossi ble t o d eter mi ne t h e 
effica c y of oral c o ntrac e pti v es as a n effe cti ve met h o d of c o ntrac e pti o n f or W O C B P w h o are 
partici pati n g i n t his st u d y. Oral estr o ge n a n d pr o g esti n h or m o nal c o ntrac e pti ves as a s ol e met h o d 
of c o ntrac e pti o n are t her ef ore pr o hi bite d. It is re q uir e d t hat all W O C B P use t w o met h o ds of 
c o ntrac e pti o n f or t he d urati o n of t he st u d y ( i.e. be gi n ni n g at 3 0 da ys pri or t o baseli ne) t hr o u g h 3 0 
da ys after t he last d ose of st u d y dr u g. T he t w o met h o ds s h o ul d i ncl u de o ne b arrier met h o d (e. g. 
dia p hra g m wit h s per mi ci dal gel, c o n d o m wit h s per mici dal gel, i ntra uteri ne d e vic es, cer vi cal ca p) 
a n d o ne ot her met h o d. T he ot her met h o d c o ul d i n cl u de oral c o ntrace pti ves (e. g. or al 
c o ntrac e pti v es, i njecta bl e c o ntr ace pti ves or c o ntrace pti ve i m pla nt) or a n ot h er barrier met h o d.  
A n y male w h o has a fe male p art ner of W O C B P has t o a v oi d bec o mi n g pre g n a nt w hile 
part ici pati n g i n t his st u d y. If mal e s u bjects ar e se x uall y acti ve a n d n ot vasect o miz e d f or at least 6 
m o nt hs, a n d if t h e s u bject’s fe male part n er is n ot s ur gicall y sterile or is n ot p ost - me n o pa usal, 
t he n o ne of t h e f oll o wi n g acce pte d m et h o ds of c o ntr ace pti o n s h o ul d be use d t hr o u g h o ut t he st u d y 
a n d f or 9 0 da ys after t he last st u d y dr u g  a d mi nistrati o n:  
•  Si m ulta n e o us use of mal e c o n d o m, a n d f or t he fe mal e part ner, h or m o nal c o ntrac e pti v es (e. g., 
birt h c o ntr ol pills, i m pl a nts, pat c h, de p ot i nje cti o n, use d si nce  at least 4 wee ks) or i ntra -
uteri ne c o ntra ce pti v e de vi ce ( pl ace d si n ce at least 4 wee ks) bef ore se x ual i nterc o urse;  
•  Si m ulta n e o us use of mal e c o n d o m, a n d f or t he fe mal e part ner, dia p hra g m wit h i ntr a va gi n all y 
a p plie d s per mici de. 
5. 6  
D e vi ati o n fr o m I n cl u si o n/ E x cl u si o n  Crit eri a  
A n y si g nifica nt e ve nt t hat d o es n ot c o m pl y wit h t he i ncl usi o n e xcl usi o n criteri a, st u d y c o n d uct, 
or st u d y pr oce d ures will b e d oc u me nte d as a d e viati o n. De viati o ns will be d oc u me nt e d a n d 
re p orte d t hr o u g h t he cli nic al 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 n c y re q uire d b y y o ur I R B/ E C. T h ere will b e n o pr ot oc ol e xce pti o ns gra nte d b y t he 
S p o ns or f or I ncl usi o n/ E xcl usi o n crit eria.  
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 s p o ns or will pr o vi de i n vesti g ati o n al pr o d uct w hi c h will i n cl u de tr oril u z ole (1 4 0  m g  a n d 6 0 
m g ) ca ps ules a n d mat c hi n g pla ce b o.  
Sites will als o be pr o vi de d wit h a Re g ulat or y bi n der, a n d IW R S Ma n ual. S o urce d o c u me nt 
creati o n is t he r es p o nsi bilit y of t he s ite. I nstr ucti o ns o n all s peci me ns c olle cte d will be pr o vi d e d 
b y a ce ntr al l a b orat or y.  
All sites will use a n El ectr o nic Data C a pt ure ( E D C) t o ol t o s u b mit st u d y d ata. Ele ctr o ni c Case 
Re p ort F or ms (e C R Fs) will be pre p are d f or all dat a c ollecti o ns.  
S ites will be pr o vi de d wit h a Bi o ha v e n a p pr o ve d pr ot oc ol a n d a n y a m e n d me nts.  

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 65 of 97 
 
Draft Version 10; 13 Oct 2022 
 
The investigator will be required to have a centrifuge, a secure locked cabinet or similar (for 
drug storage) as well as appropriate containers and dry ice for shipment and storage of blood and 
plasma samples. Enough dry ice, when indicated, should be utilized to allow samples to arrive at 
their designated laboratory in a frozen state. 
7 ELIGIBILITY ASSESSMENTS 
7.1 
Massachusetts General Hospital-Treatment Response Questionnaire for 
OCD (MGH-TRQ-OCD) 
The MGH-TRQ-OCD is a clinician rated questionnaire used to assess the subject’s response 
to standard of care treatment for OCD at screening. The subject must have an inadequate 
response to the standard of care treatment, as defined in the protocol, as documented on the 
MGH-TRQ-OCD at screening. 
7.2 
Mini Mental State Examination (MMSE) 
The MMSE is a 30-point (11-question) measure of commonly used tests to measure cognitive 
impairment. It tests five areas of cognitive function including orientation, registration, attention, 
and calculation, recall and language. 
7.3 
MINI International Neuropsychiatric Interview (MINI) 
The MINI is a structured interview for the diagnosis of psychiatric disorders that will be 
conducted at screening to confirm the diagnosis of OCD and assess for the presence of other 
major psychiatric conditions. 
7.4 
Borderline Personality Disorder Module (BPD) 
The Borderline Personality Disorder Module is a structured interview that will be conducted 
at screening to confirm the diagnosis of Borderline Personality Disorder. 
7.5 
SAFER Interview 
The SAFER Interview is a structured interview conducted remotely by a CRO (telephone 
call to subject) shortly after the screening visit is completed to confirm the diagnosis, 
treatment history and OCD severity. A SAFER pass is necessary for randomization. It will 
be conducted by trained personnel who are qualified psychiatrists and psychologists. 
Additional details about this interview will be provided in the Informed Consent Form. 
7.6 
Medical History 
A full medical history will need to be obtained at the screening visit. This will include but is not 
limited to: smoking history, cardiovascular disease, family history of OCD, and history of tic 
disorder if available. 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 6  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
7. 7  
S af et y A s s e s s m e nt s  
Safet y a n d  t olera bilit y will b e e val u ate d b y r e p ort of a d verse e ve nts ( A E) a n d b y e val u ati o n of 
a b n or maliti es a n d cli nicall y si g nifica nt c ha n g es i n p h ysical e x a mi n ati o ns, E C Gs, vit al si g ns, a n d 
la b orat or y tests. 
7. 7. 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 vital si g n meas ure me nts (t e m perat ure, bl o o d press ure, a n d heart rate) will be re c or de d 
d uri n g t he sc he d ule d visits as s pecifie d i n t he Sc h e d ule of Assess me nts/ Ti m e & E v e nts a n d as 
me dic all y n ecessar y.  
B o d y wei g ht a n d hei g ht will be re c or de d at sc h e d ule d visits. T he f oll o wi n g g ui deli nes will ai d i n 
t he sta n dar dizati o n of t hese meas ure me nts: 
1.  T he sa me sc ale s h o ul d b e use d t o wei g h a gi ve n s u bj ect t hr o u g h o ut t he  st u d y; 
2.  A  s u bject s h o ul d v oi d  j ust pri or  t o bei n g  wei g he d;     
3.  Wei g ht s h o ul d b e  rec or de d b ef ore a meal (if a p plic a ble) a n d at a p pr o xi matel y t he sa me ti me 
eac h da y; a n d    
4.  A s u bject s h o ul d be mi ni m all y cl ot h e d (i.e., n o s h oes or hea v y  gar m e nts).  
7. 7. 2  
El e ctr o c ar di o gr a m ( E C G)  
A 1 2 -Lea d E C G will b e rec or de d d uri n g t he sc h e d ul e d visits as s pecif ie d i n t he Sc he d ule of 
Assess me nts/ Ti me & E ve nts a n d as me di call y necessar y.  
7. 7. 3  
P h y si c al E x a m  
S u bjects will u n d er g o a c o m plete p h ysical e xa m i n b ot h t he Ra n d o miz ati o n a n d E xt e nsi o n P hase 
of t he st u d y. T he P h ysic al E x a m s h o ul d i n cl u de at le ast t he f oll o wi n g c o m p o n e nts: H E E N T 
( hea d, e yes, ears, n ose, a n d t hr oat), n ec k, l y m p h n o d es, l u n gs, car di o vasc ular, a b d o m e n, s ki n, 
a n d m usc ul os kel etal e val uati o n b y t he Pri nci pal I n v esti gat or or a me di call y q ualifie d dele gate .  If 
a s u bject is disc o nti n u e d f or a n y reas o n, a n att e m pt s h o ul d be ma d e t o c o n d u ct a fi n al p h ysic al 
e xa m.  
7. 7. 4  
L a b or at or y A s s e s s m e nt s  
La b orat or y  testi n g will i n cl u de t he f oll o wi n g: 
a) He mat ol o g y: he m o gl o bi n, he mat o crit, platelets, C B C wit h differe ntial a n d a bs ol ute 
ne utr o p hil  c o u nt  
b)  Ser u m C he mistr y: s o di u m, p ot assi u m, c hl ori de, c alci u m, A L T, A S T, L D H, al kali ne 
p h os p hatase, G G T, p h os p h or o us, bic ar b o nate, C P K, t otal pr otei n, al b u mi n, t ot al bilir u bi n 
(if great er t ha n 2 m g/ dl bilir u bi n will be fr acti o nat e d), gl uc ose, cre ati ni ne, B U N, uric 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
aci d, a n d pr e g na nc y t esti n g ( W O C B P). A d diti o n all y,  at scree ni n g, t ot al c h olester ol, L D L, 
H D L, tri gl yceri des, f olate, H b A 1 C, P -A m ylase or Li pase, T S H, a n d  T 4;  
c) Uri nal ysis: ma cr osc o pic e xa mi n ati o n, p H, s pecific gr a vit y, ket o nes, nitrites, ur o bili n o ge n, 
le u k oc yt e ester ase, pr otei n, creati ni n e, gl uc ose, a n d occ ult bl o o d will b e perf or me d 
d uri n g t he sc he d ule d visits as s pecifie d i n t he Sc h e d ule of Assess me nts/ Ti m e & E v e nts 
a n d as me di call y necessar y. If bl o o d, pr otei n, or le u k oc ytes, are p ositi ve micr osc o pi c 
e xami n ati o n will be p erf or me d o n a b n or mal  fi n di n gs; 
d)  S er u m pr e g n a n c y t est will b e c o n d u ct e d at s cr e e ni n g.  Uri n e pre g na nc y tests will b e 
perf or me d p ri or t o d osi n g at B aseli ne a n d at sc h e d ul e d visits, at st u d y visits w here l a b 
assess me nts are n ot perf or me d, or at t he discr eti o n of t he  I n vesti gat or.  S u bj ects will be 
pr o vi de d wit h uri n e pre g na nc y tests t o t a ke i n b et we e n e ver y 3 -m o nt h office visit d uri n g 
t he E xt e nsi o n (a n d E x p a n de d E xt e nsi o n) P hase;  
e) H Bs A g, H C V , HI V a nti b o d y detecti o n , a n d R P R (reflex  testi n g will b e d o ne f or a n y 
p ositi ve R P R)  will b e perf or m e d at scre e ni n g.  
f) Uri ne Dr u g Scree n f or ca n na bis ( me di cal a n d recr eati o nal), a m p het a mi n es (i ncl u di n g  
M D M A/ecstas y), c ocai ne, bar bit urate, P C P, be nz o di aze pi n es, tric y clic a nti d e pressa nts, 
a n d/ or o pia tes at scr ee ni n g a n d b aseli n e. Refl e x c o nfir mat or y testi n g will be c o n d uct e d 
o n all p ositi ve uri n e dr u g scree n sa m ples.  
A n y la b val ue o utsi de of t h e n or mal r a n ge m ust b e br o u g ht t o t he att e nti o n of a p h ysici a n 
(I n vesti gat or or S u b-I n vesti gat or) at t he site. T h e I n v esti gat or will i n dicate w het her or n ot a 
fla g ge d val ue is of cli nic al si g nifica n ce. I n a d diti o n, if warra nte d re p eat la bs ca n b e dra w n. 
If a partici pa nt is u na ble t o c o me i n t o t he st u d y site a n d nee ds t o ha ve safet y la bs c o n d ucte d l ocall y 
t his is acce pta bl e. T he st u d y site s h o ul d pr o vi de t he parti ci pa nt or l oc al la b or at or y wit h a 
re q uisiti o n a n d s h o ul d c olle ct t he res ults. W he n r es ults are o btai n e d, i n a d diti o n t o e nteri n g t he m 
i nt o t h e E D C, t he site s h o ul d r e dact t h e re p ort of all patie nt i d e ntifyi n g i nf or mati o n a n d se n d t he 
res ults directl y t o t he S p o ns or Me dical M o nit or.  
S p o ns or Me dic al M o nit or  
Cell: 
 
7. 7. 4. 1  
B D N F  a n d pr o B D N F  Bl o o d S a m pl e C oll e cti o n  
A bi o mar ker sa m ple will als o be c olle cte d f or plas m a brai n -deri ve d ne ur otr o p h ic fa ct or ( B D N F) 
a n d pr o B D N F . Brai n -deri ve d ne ur otr o p hic fa ct or ( B D N F) is a ne ur otr o p hi c fact or t hat r e g ulates 
s y na pse de vel o p m e nt a n d plasticit y. It is secret e d fr o m tar get cells i n a n acti vit y -de p e n de nt 
ma n ner  a n d is i nitiall y s y nt hesiz e d as a prec urs or ( pr o B D N F), w hic h is pr ote ol ytic all y pr o cesse d 
P P D
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 68 of 97 
 
Draft Version 10; 13 Oct 2022 
 
into mature factor. Measurement of both forms of neurotrophic factor may provide an assessment 
of potential effects of troriluzole on synaptic plasticity. 
Samples should be collected via antecubital venipuncture between the hours of 10 am and 2 pm, 
to minimize potential diurnal variability. Serum will be collected at the admission (baseline), and 
Week 12 of the Randomization Phase in all subjects. If subjects enter the Extension Phase of the 
study, a BDNF sample will be collected at Week 48 of the Extension Phase. BDNF samples are 
not collected in the Expanded Extension Phase. A blood sample (5 mL) will be collected in 
anticoagulant-free tubes and kept at room temperature for 30 minutes, and then spun to isolate 
serum at 1000g Å~ 15 min at room temperature. Serum will be collected and kept at -20°C 
before shipping on dry ice.  
7.7.4.2 
Pharmacokinetics 
A pharmacokinetic sample will be collected at Week 4, Week 8,  and Week 12 of the 
Randomization Phase. Subjects should take their dose at their routine time on the days of these 
visits. Date and time of doses on the day of visits and day prior will be collected in case report 
forms along with time of last meal for entry into the eDC system. Subjects who are able to 
schedule a morning visit for Week 4 and Week 8 can be instructed to hold their dose of study 
drug that morning until after a PK trough sample is obtained, if possible and appropriate. 
Additionally, PK samples should be drawn if there are any SAEs that could possibly be drug-
related or severe AEs that could be drug-related. 
7.7.4.3 
Pharmacogenetics 
A pharmacogenetics blood sample will be obtained at baseline and end of study (Week 12 
Randomization Phase) for possible future exploratory analysis investigating how genetic 
variation may determine troriluzole efficacy and safety.  All subjects will sign a 
pharmacogenomics ICF indicating whether they are consenting to or not consenting to provide a 
pharmacogenetic blood sample.  All subjects will be informed that consenting to provide a blood 
sample for pharmacogenetic analysis is optional and does not affect participation in the study.    
DNA samples will be stored indefinitely from subjects who have provided written informed 
consent unless a written request for destruction of the sample is provided by the subject to the 
site which conducted the Biohaven-sponsored clinical trial.  This written request provided by the 
subject requesting destruction of the subject’s pharmacogenetic samples should be provided by 
the site to the sponsor. 
7.7.4.4 
Pregnancy Testing 
Pregnancy testing should be performed on all women of childbearing potential (WOCBP) during 
both the Randomization Phase and Extension Phase of the study. Refer to the Schedule of 
Assessments/Time & Events for detailed time points in which serum pregnancy tests and urine 
pregnancy tests are required. Urine pregnancy testing may also be done at the discretion of the 
Investigator at any time during the study. Subjects should not continue in the study if the 
pregnancy test is positive at any time. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 6 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
7. 7. 4. 5  
E v al u ati o n of L a b or at or y A s s e s s m e nt s  
T he ma n a ge m e nt of a b n or m al L F Ts ar e descri b e d herei n. Sc he d ul e d L F Ts ( A L T, A S T, bilir u bi n, 
al kali ne p h os p hat ase) at W ee k 4 a n d t hr o u g h We e k 4 8 visits (see Sc he d ul e of Assess me nts f or 
details) will be e val u ate d b y a p h ysi cia n or ot her q ualifie d me di cal p ers o n ne l.  
If A S T or A L T val ues are bet wee n 3 x U L N a n d < 5 x U L N, t he i n vesti g at or will me dicall y 
e val uate t h e s u bject.  Me dical assess me nt of t h e s u bje ct ca n i ncl u d e t he f oll o wi n g:  
•  M ust i ncl u de re p eat L F T assess me nts ( A L T, A S T, t otal a n d direct bilir u bi n, al kali n e  
p h os p hatase, P T, a P T T, I N R) wit hi n 1 wee k a n d f oll o w u ntil res ol uti o n. T he fr e q ue nc y  of t h e 
re peat tests will b e cli nicall y base d o n traj ect or y of c ha n ge (e. g., i m pr o vi n g, sta ble vs 
i ncreasi n g). T hese tests ca n be perf or me d eit her at a l ocal, or pr efera bl y, ce ntr al l a b  
•  Assess me nt of A Es, usa ge of c o nc o mit a nt me dicati o ns, e x p os ure t o p ote ntial h e patic  t o xi ns, 
ris k fact ors f or he patitis or alc o h olic li ver dise ase 
•  Base d o n o verall cli nical prese nt ati o n (se v erit y a n d e xte nt of l a b a b n or m alities; rate of  
c ha n ge of l a b val ues), a d diti o n al e v al uati o ns (as o utli ne d u n der t h e sce nari o of  A L T/ A S T > 
5 x U L N) ma y be c o nsi dere d.  
If t he We e k 4  or Wee k 8  visit s h o ws A L T or A S T > 5 x U L N, t he  i n vesti g at or will assess t his as a 
p ote nti al S A E . T he s u bj ect will be ma na ge d as a p pr o priate, i ncl u di n g: 
•  St u d y me dic ati o n m ust be disc o nti n ue d i m m e diatel y  
•  Bri n g s u bject i n f or p h ysical e xa m a n d e val uati o n.  
○ Assess f or ri g ht heart fail ure, h y p ote nsi o n, a n d si g ns/s y m pt o ms of alc o h ol  a b use  
○ A ssess f or e x p os ure t o t o xic diet ar y/ her bal s u p ple m e nts a n d/ or prescri pti o ns  dr u gs t hat 
are ass ociate d wit h he p ati c effe cts, s uc h as ac eta mi n o p he n;  
○ A ssess f or p ote ntial e x p os ure t o e n vir o n me ntal t o xi ns 
○ E val uate f or a b d o mi nal p ai n, s ple n o me gal y, he pat o me gal y  
•  Re peat L F Ts ( A S T, A L T, t otal a n d dire ct bilir u bi n, al k ali n e p h os p hatase) as s o o n a s 
p ossi ble, wit h eit her a l ocal la b or pref era bl y ce ntr al la b; a n d, f oll o w t o res ol uti o n;  
•  Or der ot her la bs t ests t o r ule -o ut ot her c a uses of la b a b n or maliti es a n d t o assess e xte nt  of 
he pati c effects  
○ c oa g ulati o n fa ct ors ( P T, a P T T , I N R) 
○ He patitis A, B a n d C ser ol o gies  
○ E bstei n -Barr vir us ser ol o g y  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 7 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
•  Assess A Es  
•  C o nsi der gall bla d der or d u ctal i ma gi n g st u dies if pr ese ntati o n s u g gests p ote ntial f or  g all 
st o nes. 
E ntr y i nt o t he E xte nsi o n ( or E x p a n de d E xt e nsi o n) P hase re q uires c o nti n ue d i m pr essi o n t hat 
o pe n -la bel tre at me nt offers a n a cce pta bl e ris k -be nefit pr ofile. If la b a b n or malities i n t he 
Ra n d o miz ati o n P hase are  p ote ntiall y cli ni call y si g nifica nt t he n tr eat me nt wit h st u d y dr u g i n t he 
E xte nsi o n P hase s h o ul d  n ot b e gi n u ntil s uc h l a bs near n or mal li mits or i n t he case of el e vat e d 
tra nsa mi n ases ( A L T or A S T) are wit hi n 3 x U L N. If r es ults fr o m t he sc h e d ule d Wee k 1 2  
assess me nt s h o w e mer ge nce of  p ote ntiall y cli nic all y si g nifica nt la b a b n or malities a n d t he s u bj ect 
has alrea d y st arte d o pe n -la bel tr oril uz ol e, t he n la bs m ust be re pe ate d a n d t he i n v esti gat or, base d 
o n cli ni cal i m pressi o n c o n cer ni n g t h e  nat ur e a n d se v erit y of res ults, ma y de ci de t o c o nti n u e 
tr oril uz ole. I n t h e case of A S T or A L T > 5 x U L N, r e -c halle n ge wit h st u d y dr u g will n ot be 
all o we d.  
7. 7. 5  
S h e e h a n S ui ci d alit y Tr a c ki n g S c al e ( S h e e h a n S T S)  
T he S hee ha n S T S ( S -S T S) is a pr os pecti ve, patie nt s elf -re p ort e d or cli nici a n a d mi nister e d rati n g 
scale t h at c o ntai ns 1 6 q uesti o ns t o trac k b ot h tre at m e nt-e mer g e nt s uici dal i deati o n a n d be h a vi ors 
4 6 ,4 7. T he S-S T S will be c o m plete d o n a p a per f or m at t he sit e. At t he scr ee ni n g visit, t h e recall 
peri o d f or c o m pleti n g t he S -S T S is 6 m o nt hs pri or; a t all ot her visits, t he re call peri o d f or 
c o m pleti n g t h e S -S T S is si nce t he last visit. S u bjects w h o ha ve a S -S T S sc ore > 0 s h o ul d be 
e val uate d b y t h e i n vesti gat or.  If t h e i n vesti gat or d eter mi nes t hat a s u bje ct is at ris k of s uici de or 
self-har m, a p pr o pri ate meas ures t o e ns ure t he s u bj ect’s safet y a n d o btai n me ntal he alt h 
e val uati o n m ust b e i m ple m e nte d. T h e s u bject m ust i m me di atel 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 d e 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 S p o ns or. 
7. 8  
Cli ni c al O ut c o m e A s s e s s m e nt s  
Trai ni n g will be pr o vi de d f or all cli nic al o ut c o me assess me nts t hr o u g h eit her di d actic , vi de o 
certificati o n, a n d/ or o nli ne trai ni n g.   
T he or der of t h e tests s h o ul d i n cl u de t h e a d mi nistrati o n of t he Y -B O C S pri or t o ot her cli ni cal / 
safet y o utc o me assess me nts, f oll o we d b y t he ot h er cli nical o utc o me assess me nts .   
7. 8. 1  
Y al e -Br o w n O b s e s si v e C o m p ul si v e S c al e ( Y -B O C S)  
T he Y -B O C S is a cli ni cia n -a d mi nistere d scale use d e xte nsi vel y i n resear c h a n d cli nic al pra cti ce 
t o b ot h rat e se verit y of O C D a n d t o m o nit or i m pr o ve me nt d uri n g treat me nt. It is desi g n e d t o rat e 
t he se verit y of o bsessi o ns a n d c o m p ulsi o ns as well as t he  t y pe of s y m pt o ms i n patie nts wit h 
O C D. T he scale c o nsists of 1 0 ite ms, t h e first 5 ite ms assess o bsessi o ns a n d t he last 5 ite ms 
assess c o m p ulsi o ns. S u bscale sc ore s ca n be cal c ulate d f or o bsessi o ns a n d c o m p ulsi o ns, eac h o n a 
scale of 0 –  2 0. A t ot al sc ore ra n gi n g fr o m 0 –  4 0 c a n t he n be c orr elate d t o o ver a ll se v erit y.  T he 
Y -B O C S S y m pt o m C hec klist will be use d as a n ai d f or i de ntif yi n g c urre nt s y m pt o ms.  

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 71 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Raters must be trained and pre-approved by sponsor or sponsor representative (i.e. CRO) to rate 
subjects on the Y-BOCS.  Raters must complete training and receive their certification prior to 
administering the Y-BOCS to study subjects.  
7.8.2 
Sheehan Disability Scale (SDS) 
The Sheehan Disability Scale (SDS) is a patient-rated measure of functional disability in 
domains of work, social and family life.  The SDS has demonstrated sensitivity to treatment 
effects in numerous randomized controlled trials in populations with varied diagnoses (70).  The 
assessment is a three item questionnaire measuring disease-related disruption of work, social life 
and family life.  Respondents evaluate impairment on an 11 point scale from 0 -10 with anchor 
definitions. The 3 items can also be summed into a single dimensional measure of global 
functional impairment that rages from 0 (unimpaired) to 30 (highly impaired).  
Subjects may indicate that item 1 of the SDS (Work/School) is not applicable to them by 
checking a box labeled “I have not worked / studied at all during the past week for reasons 
unrelated to the disorder.” For these subjects item 1 of the SDS is not scored. However, subjects 
that were unable to work or study due to reasons related to the disorder must complete item 1. 
If a subject checks the “not working” box for the Work/School item, you MUST check 
compliance to this instruction, before the visit ends. 
7.8.3 
Clinical Global Impression – Severity Scale (CGI-S) 
The CGI-S is a clinician rated assessment of the subject’s current illness state on a 7 point 
scale. A higher score is associated with greater illness severity.  The CGI-S will be 
conducted at screening and baseline and subsequent study visits as indicated in the Schedule 
of Assessments and Events. 
7.8.4 
Brown Assessment of Beliefs Scale (BABS) 
The BABS is a semi-structured, rater-administered scale that assesses insight/delusionality both 
dimensionally (as a continuum of insight) and categorically (i.e., dichotomously – for example, 
delusional vs. nondelusional) regarding patient beliefs. These beliefs include the delusions as 
well as the beliefs that may underlie obsessional thinking. The BABS is a 7-item scale that 
assesses insight/delusionality during the past week.  
BABS items assess the person’s conviction that their belief is accurate, perception of others’ 
views of the belief, explanation for any difference between the person’s and others’ views of the 
belief, whether the person could be convinced that the belief is wrong, attempts to disprove the 
belief, insight (recognition that the belief has a psychiatric/psychological cause), and 
ideas/delusions of reference related to the belief. The first six items are summed to create a total 
score that ranges from 0 to 24; higher scores indicate poorer insight. Item 7 is not included in the 
total score, because referential thinking is characteristic of some but not all disorders.  

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 72 of 97 
 
Draft Version 10; 13 Oct 2022 
 
7.8.5 
Quick Inventory of Depressive Symptomatolgy – Self Report (QIDS-SR) 
The QIDS-SR is a self-report, 16 item questionnaire that subjects will use to rate symptoms 
of depression.  Each item is rated 0-3.  For symptom domains that require more than one 
item, the highest score of the item relevant for each domain is taken.  Total scores range 
from 0-27 and are obtained by adding the scores for each of nine symptom domains.  Higher 
scores indicate higher levels of depression.  
7.8.6 
Beck Anxiety Inventory (BAI) 
The BAI is a 21 question multiple choice self-report questionnaire that subjects will use to rate 
symptoms of anxiety using a 4 point Likert scale.  Scores on the BAI range from 0 to 63.  Higher 
scores indicate higher levels of anxiety symptoms. 
8 EARLY DISCONTNUATION OF STUDY 
All subjects who discontinue study treatment early should complete the 2-Week Post Dose Visit. 
The only exception to this requirement is when a subject withdraws consent for all study 
procedures or loses the ability to consent freely (i.e. is imprisoned or involuntarily incarcerated 
for the treatment of either a psychiatric or physical illness). 
9 STUDY DRUG MANAGEMENT 
9.1 
Description of Study Drug 
9.1.1 
Investigational Product 
An investigational product, also known as investigational medicinal product in some regions, is 
defined as follows: 
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a 
clinical study, including products already with a marketing authorization but used or assembled 
(formulated or packaged) in a way different from the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form. 
The investigational product should be stored in a secure area according to the local regulations. It 
is the responsibility of the investigator to ensure that the investigational product is only 
dispensed to study patients. The investigational product must be dispensed only from official 
study sites by authorized personnel according to local regulations. 
In this protocol, the investigational products are: troriluzole capsules 140 mg and 60 mg and 
matching placebo during the randomization phase. 
During the first 4 weeks of extension phase study drug will remain blinded. Subjects who were 
on troriluzole during the Randomization phase will continue on their same dose during the 
Extension Phase.  Subjects re-entering the study in the Expanded Extension Phase will continue 
on the same dose as the initial 48 week Extension Phase. All subjects who were on placebo 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 7 3  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
d uri n g t he Ra n d o miz ati o n P hase will rec ei ve 1 4 0 m g tr oril uz ole f or t h e first f o ur wee ks of t he 
E xte nsi o n P hase f oll o we d b y 2 0 0 m g.   tr oril uz ole will be pr o vi de d as a f or m ulate d ca ps ul e.  
9. 1. 2  
P a c k a gi n g, S hi p m e nt a n d St or a g e  
Cli nic al Trial Materi als s h o ul d be st ore d at c o ntr olle d te m per at ure b et wee n 2 0 °C a n d 2 5 ° C ( 6 8 °F 
-7 7 °F) , wit h e xc ursi o ns per mitte d bet wee n 1 5 °C a n d 2 0 ° C ( 5 9 °F -6 8 °F), i n a se c ure, t e m per at ure 
c o ntr oll e d, li mit e d ac cess area.  
T he  me dicati o ns will b e st ore d i n a l oc ke d, e n vir o n m e ntall y -c o ntr olle d me dic ati o n r o o m wit h 
restrict e d acc ess. C o ntai ner(s) will bear a la b el c o ntai ni n g at least t he na me of t he st u d y dr u g, l ot 
a n d/ or bat c h n u m ber  a n d st ora ge c o n diti o ns .  
9. 2  
D o s e a n d A d mi ni str ati o n  
9. 2. 1  
R a n d o mi z ati o n P h a s e  
D uri n g t he ra n d o mizati o n p hase, all s u bje cts will b e ra n d o miz e d t o re cei ve 1 4 0 m g or pla ce b o, 
Q D, f or t he first f o ur ( 4) w ee ks of t he Ra n d o mizati o n P hase.  S u bjects will t he n be i ncrease d t o 
2 0 0 m g ( pr o vi de d as o ne b ottl e  of 1 4 0  m g a n d o ne b ottle of 6 0  m g) or matc hi n g place b o f or t he 
d urati o n of t h e Ra n d o mizati o n P hase.   D o w n titrati o n bac k t o 1 4 0 m g will o nl y b e all o we d t o 
a d dress  t olera bilit y iss ues. If a s u bject d o w n titrates t he y will ne e d t o sta y o n t hat d ose f or t he 
d urati o n of t h e R a n d o mizati o n P hase.  
It is rec o m me n de d t hat all patie nts i n gest st u d y dr u g o nce e ver y d a y i n t he m or ni n g 
(a p pr o xi matel y at t h e sa me ti me eac h d a y), wit h o ut  r e gar d t o m eals.  
•  If s u bjects ha ve diffic ult y t olerati n g m or ni n g d osi n g (s uc h as e x perie nci n g se dati o n) t he n t he 
i n vesti gat or ma y p er mit t he s u bj ect t o s witc h t o ni g ht ti m e d osi n g (a n d d oc u me nt t his c ha n g e 
i n t he s u bje ct’s rec or ds). 
9. 2. 2  
E xt e n si o n P h a s e  
S u bjects c o m pleti n g t he R a n d o mi zati o n P hase will b e offere d a p pr o xi mat el y 4 8  wee ks of  
tr oril uz ole tr eat me nt as l o n g as t he PI belie ves o pe n-la bel treat me nt offers a n ac ce pt a ble ris k- 
be nefit pr ofile. S u bj ects w h o a gree t o e nt er t he E xte nsi o n P hase will r ec ei ve tr oril uz ole.   
I n or der t o mai ntai n t he bli n d of t he Ra n d o mi zati o n P hase a n d t o safel y i ncrease all s u bj ects t o 
2 0 0  m g after E xte nsi o n P hase Wee k 4 , t h e first 4 we e ks of t he E xt e nsi o n P hase will r e mai n 
bli n de d.  
If a s u bject was o n acti ve treat me nt in t h e Ra n d o miz ati o n P hase, t h e y will st art t h e E xt e nsi o n 
P hase o n t he sa me d ose t hat t he y were t a ki n g at We e k 1 2 of t he Ra n d o mizati o n  P hase.    
If a s u bject r ecei v e d pla ce b o i n t he R a n d o miz ati o n P hase , t he y will be s witc h e d i n a bli n de d 
ma n ner t o 1 4 0 m g f or t he first 4 wee k s of t he E xte nsi o n P hase .  

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 74 of 97 
 
Draft Version 10; 13 Oct 2022 
 
After Extension Phase Week 4 all subjects will be on open label troriluzole 200 mg. Down 
titration will only be allowed to address tolerability issues. Subjects who enter the Extension 
Phase on 140 mg due to tolerability issues can be rechallenged to increase to 200 mg beginning 
at Extension Week 4 at investigator discretion. 
Subjects who complete the 48-week Extension Phase and will be continuing directly into the 48-
week Expanded Extension Phase with no dose interruption will have their first visit 12 weeks 
after the Extension Week 48 visit. Therafter, subject will undergo visits every 12 weeks until 
Week 96 of the Expanded Extension Phase as outlined in Table 3 (Schedule of 
Assessments/Time & Events – Expanded Extension Phase).  
Subjects who previously completed the Extension Week 48 visit and exited the study, will have 
the opportunity to return and receive an additional 48 weeks of open-label treatment with 
troriluzole in the Expanded Extension Phase provided it has not been more than 3 months since 
they completed the study and the PI believes it offers an acceptable risk-benefit profile. 
Returning subjects who have been off study medication for less than 4 weeks will undergo an 
abbreviated Baseline visit before re-entering the study. Returning subjects who have been off 
study medication for 4 weeks or more will be required to undergo a full Baseline visit. In 
addition, for returning subjects, safety laboratory assessments will be performed 4 and 8 weeks 
after re-starting study medication. Thereafter, study visits in the Expanded Extension Phase will 
be every 12 weeks until Week 48. All subject will undergo a termination visit two weeks after 
the last dose of study drug. 
Subjects entering the Expanded Extension Phase will continue with the same dose taken at the 
end of the initial Extension Phase. Down titration after the first four weeks of the Expanded 
Extension Phase will only be allowed for tolerability purposes.  Subjects who enter the Expanded 
Extension Phase on 140 mg due to tolerability issues can be rechallenged to increase to 200 mg 
after the first 4 weeks at PI discretion.    
Due to the change of dose throughout the study it is imperative that subjects are educated and 
reminded to take one capsule from each bottle for each dose. 
9.2.3 
Method of Assigning Patient Identification 
The investigator or designee will need to access an Interactive Web-based Response System 
(IWRS) in order to register each subject in each study phase. Initially the investigator or designee 
will enter the subject into the study at the Screening Visit after informed consent is obtained and 
a subject number is assigned. After completion of all screening evaluations, all eligible subjects 
will be randomized, in a 1:1 ratio to receive either placebo (QD) or  troriluzole. Treatment 
assignments will be obtained by the investigator (or designee) via the IWRS system. 
Investigational sites will access the IWRS at each scheduled study visit throughout the 
Randomization Phase. The IWRS system will assign specific bottle numbers for all blinded study 
drug to be dispensed to the subject. Once a bottle has been assigned it cannot be dispensed to 
another study subject. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 75 of 97 
 
Draft Version 10; 13 Oct 2022 
 
Once a subject completes the Randomization Phase or if a subject is discontinued early from the 
study, the investigator or designee must access the IWRS to discontinue the patient from 
participation in the study.  
Subjects who complete 12 weeks of treatment in the Randomization Phase may be eligible for an 
Extension Phase of the study. The investigator or designee must access the IWRS to enter the 
subject in the Extension Phase, or the Expanded Extension Phase if the subject previously 
completed the initial 48-Week Extension Phase, left the study, and is re-entering the study within 
3 months for an additional 48 weeks of open-label treatment with truriluzole. Investigational 
sites will access the IWRS at each scheduled study visit throughout the Extension Phase and 
Expanded Extension Phase) to track patient enrollment. If a subject has to delay the 
Randomization Phase Week 12 visit due to concerns about COVID-19, the subject should remain 
on current blinded drug until the subject is in the office. Subjects will not transition to extension 
phase until completing the Week 12 visit in person. If study site needs to send drug via certified 
and tracked courier (and this is acceptable to the institution) because an in person visit is not 
possible due to COVID-19 concerns, this is permissible per study. Site should contact Sponsor 
for IWRS instructions to dispense blinded drug that may be needed for subjects who are unable 
to come into the office for Week 12 visit and require drug to be shipped. 
Study medication will be assigned via the IWRS system in the Extension Phase (and Expanded 
Extension Phase). The first 4 weeks of treatment in the Extension Phase will be blinded in order 
to maintain the blind in the randomization phase.  From Extension Phase Week 4 on, the study 
will be open-label. Sites will be responsible for recording the bottle numbers dispensed to the 
subject on the Drug Accountability Form provided in the Regulatory Binder, as well as ensure 
appropriate documentation of dispensation in the subject’s medical record.  Once a subject 
completes the Extension Phase (or Expanded Extension Phase) or if a subject is discontinued 
early from the Extension Phase of the study, the investigator or designee must access the IWRS 
to document the discontinuation of the subject from participation in the study. 
9.2.4 
Selection and Timing of Dose and Administration 
During the randomization phase of the study, subjects will be randomized to receive placebo 
(QD) or troriluzole (200 mg QD). Open label troriluzole will be provided during the extension 
(and Expanded Extension) phase.  Study Drug will be dispensed at the baseline visit. Subjects 
should take the first dose the day after the baseline visit.  Study medication should be 
administered in the morning without regard to meals. 
9.2.5 
Dose Modifications 
Randomization Phase:  Subjects will receive 140 mg or Placebo for the first four (4) weeks and 
will then be increased to 200 mg or placebo for the duration of the study.  Down titration to 140 
mg will be allowed after Week 4, only in order to address tolerability issues. If a subject is down 
titrated they will need to remain at 140 mg for the remainder of the Randomization Phase. 
Extension Phase: Subjects entering the Extension phase will continue on the same dose that was 
taken at the end of the Randomization phase.  Subjects receiving placebo in the randomization 
phase will be switched in a blinded manner to 140 mg for the first 4 week, and will then be 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 76 of 97 
 
Draft Version 10; 13 Oct 2022 
 
increased to 200 mg (at the Week 4 visits).  Down titration to 140 mg will only be allowed to 
address tolerability issues. Subjects who enter the Extension Phase on 140 mg due to tolerability 
issues can be rechallenged to increase to 200 mg beginning at Extension Week 4 at PI discretion.  
All visits after week 4 will be open-label. Subjects re-entering the study in the Expanded 
Extension Phase will continue on the same dose as the initial 48 week Extension Phase. 
For subjects who do not tolerate their study treatment (140 mg or 200 mg), the investigator may 
permit them to switch to night time dosing if there is reason to believe that may help tolerability. 
Any such changes must be documented by the investigator.  If the subject is receiving 140 mg 
and this switch in dosing time does not result in acceptable tolerability then dosing should be 
discontinued.  
9.3 
Blinding and Unblinding 
Blinding is critical to the integrity of this clinical study. However, in the event of a medical 
emergency or pregnancy in an individual subject, in which knowledge of the investigational 
product is critical to the subject’s management, the blind for that patient may be broken by the 
treating physician. 
Before breaking the blind of an individual subject’s treatment, the investigator should have 
determined that the information is necessary, i.e., that it will alter the subject’s immediate 
management. In many cases, particularly when the emergency is clearly not investigational 
product related, the problem may be properly managed by assuming that the subject is receiving 
active product without the need for unblinding. Unblinding will be managed via the IWRS 
system.  
A pharmacokineticist, IWRS randomization vendor, and pharmacovigilance role may be 
unblinded before data are more generally unblinded after the Randomized Phase of the study. 
Except as noted above, other members of the BHV research team will remain blinded. 
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt to 
preserve the blind is made. 
9.4 
Treatment Compliance 
Responsible study personnel will dispense the study drug. Accountability and compliance 
verification should be documented in the subject’s study records. 
Subjects will be counseled on the importance of taking the study drug as directed at all study 
visits. If poor compliance continues, (i.e., multiple missed doses resulting in less than 80% 
overall compliance during the Randomization Phase), discontinuation of the subject from the 
trial should be considered. 
If the study site needs to send drug overnight via certified and tracked courier and this is 
acceptable to the institution because a visit is absolutely not possible to be completed due to the 
COVID-19 pandemic, this is permissible per study. The Sponsor should be consulted prior to 
shipping drug.  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 7 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
9. 5  
D e str u c ti o n a n d R et ur n of St u d y Dr u g 
All u n use d a n d/ or partiall y use d st u d y dr u g ca n b e se nt bac k t o t he dr u g de p ot  f or destr ucti o n 
o nl y  after b ei n g i ns pe cte d a n d r ec o ncile d b y t he res p o nsi ble B H V St u d y m o nit or or t h e s p o ns or’s 
desi g nee.  
If it is site p olic y t o destr o y st u d y dr u g o n sit e, it is t he i n vesti g at or’s res p o nsi bilit y t o e ns ure t hat 
arra n ge m e nts ha ve be e n ma d e f or t he dis p osal, p r oce d ures f or pr o per dis p osal ha ve be e n 
esta blis he d acc or di n g t o t he a p pli ca bl e re g ul ati o ns, g ui deli n es a n d i nstit uti o n al pr oc e d ures, a n d 
a p pr o priat e rec or ds of t he dis p osal ha ve b ee n d oc u m e nte d. T h e u n use d st u d y dr u gs ca n o nl y be 
destr o ye d aft er bei n g i ns pecte d a n d rec o n cil e d b y t he res p o nsi ble B H V St u d y m o nit or or t h e 
s p o ns or’s desi g nee. 
1 0  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 w ar d me di cal o cc urre nc e or w orse ni n g of a 
pre -e xisti n g me di cal c o n diti o n i n a patie nt or cli nic al i n vesti ga ti o n patie nt a d mi nister e d a n 
i n vesti gati o nal ( me dici n al) pr o d uct a n d t hat d oes n ot necessaril y h a ve a c a usal relati o ns hi p wit h 
t his treat me nt. A n A E ca n t her ef ore be a n y 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 x a m pl e)  s y m pt o m, or disease te m p orall y ass ociat e d wit h t h e 
use of t he i n vesti gati o nal pr o d u ct, w het her or n ot c o nsi dere d rel ate d  t o t he i n v esti gati o nal 
pr o d uct.  
A d verse e ve nts ca n be s p o nt a ne o usl y re p orte d or elicite d d uri n g a n o pe n -e n d e d q uesti o ni n g, 
e xa mi n ati o n , or e val uati o n of a p ati e nt. I n or der t o pr e ve nt re p orti n g bi as, patie nts s h o ul d n ot be 
q uesti o ne d re g ar di n g t h e s pecifi c occ urr e nce of o n e or m ore A Es. 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 h e i nitiati o n of st u d y dr u g.  
1 0. 1  S eri o u s A d v er s e E v e nt s  
T here ar e 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).  
1 0. 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 S A E is a n y e ve nt t hat me ets a n y of t he f oll o wi n g criteri a at a n y d ose:  
•  Deat h;  
•  Life -t hr eat e ni n g; 
•  I n patie nt h os pitaliz ati o n or pr ol o n gati o n of e xisti n g h os pitali zati o n;  
•  Persiste nt or si g nifi ca nt  disa bilit y/i nc a pacit y;  
•  C o n ge nital a n o m al y/ birt h def ect i n t he offs pri n g of a s u bject w h o rec ei ve d  tr oril uz ole; 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 7 8  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
•  Ot her: I m p ort a nt m e dical e ve nt s t hat ma y n ot r es ult i n deat h, be life-t hreat e ni n g, or re q uir e 
h os pitali zati o n, ma y b e c o nsi dere d a n S A E w he n, base d u p o n a p pr o priat e me dical j u d g me nt, 
t he y ma y je o par dize t h e s u bject a n d m a y re q uir e me dical or s ur gi cal i nter ve nti o n t o pr e ve nt 
o ne of t he o ut c o mes liste d i n t his defi niti o n. E xa m pl es of s uc h e ve nts are ( b ut n ot li mite d  t o): 
○ I nte nsi ve tr eat me nt i n a n e m er ge nc y r o o m or at h o m e f or aller gi c br o nc h os pas m;  
○ Bl o o d d yscrasias or c o n v ulsi o ns t h at d o n ot r es ult i n i n pati e nt h os pit ali zati o n;  
○ De vel o p me n t of dr u g de pe n de n c y or dr u g a b use;  
○ P ote ntial dr u g i n d uc e d li v er i nj ur y (see se cti o n  1 0. 1. 7 ). 
1 0. 1. 2  
D efi niti o n of T er m s  
Life t hr eat e ni n g: A n A E is life t hre ate ni n g if t h e s u bj ect was at i m m e diate ris k of deat h fr o m t h e 
e ve nt as it occ urre d; i.e., it d oes n ot i ncl u d e a re acti o n t hat if it ha d o cc urre d i n a m ore seri o us 
f or m mi g ht h a ve c a use d deat h. F or e x a m pl e, dr u g i n d uce d he patitis t hat r es ol ve d wit h o ut 
e vi de nc e of he patic fail ure w o ul d n ot be c o nsi d ere d life t hre ate ni n g e ve n t h o u g h dr u g i n d uce d 
he patitis ca n b e fatal.  
H os pitaliz ati 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 ni cal pr o ce d ures t h at ar e n ot t he r es ult of a n A E (e. g., ele cti v e 
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 der e 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 oc e d ur e, t hat o cc urre nc e m ust be r e p orte d as a n 
A E, eit her 'seri o us' or ' n o n -seri o us' ac c or di n g t o t he us ual crit eria.  
I n ge neral, h os pitalizati o n si g nifies t hat t he s u bje ct h as bee n det ai ne d ( us uall y i n v ol vi n g at least 
a n o ver ni g ht st a y) at t he h os pit al or e m er ge nc y war d f or o bser vat i o n a n d/ or treat me nt t hat w o ul d 
n ot ha ve be e n a p pr o priate i n t he p h ysicia n's office or o ut pati e nt setti n g. W h e n i n d o u bt as t o 
w het her ' h os pitalizati o n' occ urre d or w as ne cessar y, t he A E s h o ul d be c o nsi der e 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 B H V 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 g e nc y r o o m or ot her h os pital de part me nt < 2 4 h o urs t h at d oes n ot r es ult i n 
a n a d missi o n ( u nl ess 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 dic al/s ur gical  pr oc e d ure;  
•  R o uti ne he alt 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 nter e d f or a n ot her life ci rc u msta nc e t hat c arries n o beari n g o n he alt h a n d 
re q uires n o me dical i nter v e nti o n (i.e., l ac k of h o usi n g, care-gi v er res pite, f a mil y 
circ u mst a nces).  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 7 9  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
Disa bilit y/i nc a pacitati n g: A n A E is i n ca pacitati n g or disa bli n g if t he e x p erie nc e 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 n cti o ns.  
1 0. 1. 3  
Cl a s sifi c ati o n of A d v er s e E v e nt s  
T he se verit y of all A Es m ust be rec or d e d i n t h e e C R F a n d o n t h e S A E F or m, if a p plica ble. T h e 
se verit y or i nte nsity of a n A E refers t o t h e e xt e nt t o w hic h it aff ects t h e s u bject’s dail y a cti viti es. 
T he se verit y of e ve nts s h o ul d be gra de d as mil d, m o derate or se v ere .  
T he I n vesti g at or’s assess me nt of a n A Es rel ati o ns hi p t o st u d y dr u g is part of t h e d oc u m e ntati o n 
pr ocess b ut is n ot a fa ct or  i n d eter mi ni n g w hat is or is n ot re p orte d i n t he st u d y. If t h ere is a n y 
d o u bt as t o w het her a cli nical o bser vati o n is a n A E, t he e ve nt s h o ul d b e re p orte d. T he 
relati o ns hi p or ass ociati o n of t h e st u d y dr u g i n ca usi n g or c o ntri b uti n g t o t h e A E will b e 
c haracteriz e d  as eit her n ot r elate d  or r elate d.  
1 0. 1. 4  
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 patie nt’s writte n c o nse nt t o p artici pat e 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 n cl u di n g t h ose t h o u g ht t o b e ass ociate d wit h 
pr ot oc ol -s pecific pr oc e d ures. All S A Es m ust be c olle cte d t h at oc c ur d uri n g t he scr ee ni n g p eri o d 
a n d wit hi n 3 0 da ys of disc o nti n uati o n of d osi n g. T h e i n vesti gat or s h o ul d re p ort a n y S A E 
occ urri n g after t hese ti m e peri o ds t h at is  belie v e d t o be relate d t o st u d y dr u g or pr ot oc ol -s pecific 
pr oce d ures.  
A n S A E re p ort s h o ul d be c o m pl ete 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 i n vesti gat or b eli e ves t hat a n S A E is n ot rel ate d t o t he st u d y dr u g, b ut is p ote ntiall y rel ate d 
t o t he c o n diti o ns of t h e st u d y (s uc h as a wit h dra wal of pre vi o us t hera p y or a c o m plicati o n relat e d 
t o st u d y pr oce d ure), t he rel ati o ns hi p s h o ul d b e s pecifie d i n t h e narrati ve secti o n of t h e S A E 
Re p ort F or m.  
S A Es, w het her relat e d or n ot rel ate d t o st u d y dr u g, o ver d ose, p ote ntial dr u g i n d uce d li ver i nj ur y 
a n d pre g na ncies m ust be re p orte d wit hi n 2 4 h o urs of t he I n vesti g at or be c o mi n g a war e of t he 
e ve nt. F or t his st u d y we will be c a pt uri n g S A Es t hr o u g h electr o nic d ata c a pt ure ( E D C) a n d o n 
t he S A E f or m.  
T he I n vesti g at or is res p o nsi bl e f or re p orti n g all S A Es a n d all Ot her I m p orta nt Me dical E ve nts 
t o 
 i m me diatel y via t ele p h o n e, u p o n o bser vi n g or lear ni n g of t he e ve nt. 
 will t he n 
i m me diat el y n otif y t he Bi o ha ve n Me dical M o nit or of t he e ve nt.  T he S A E f or m m ust t he n be 
s u b mitte d t o 
 wit hi n o ne w or ki n g da y. T h e I n vesti gat or is res p o nsi ble f or s u b mitti n g all 
a p plic a ble e ve nts t o t he I n de pe n d e 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 m e nts. A d diti o n all y, t he I n vesti gat or, or desi gnate d staff, is res p o nsi ble  f or e nt eri n g t h e 
S A E i nf or mati o n i n t he Ele ctr o ni c Data Ca pt ure ( E D C) s yste m (i.e.: e ve nt ter m, st art st o p dates, 
ca usalit y, se verit y).   
A d diti o nall y, a n y seri o us a d v erse e x peri e nce m ust b e  re p orte d i m m e di atel y or n o l ater t h a n 
2 4 h o urs  after a ware ness of t he e v e nt t o t he 
 de p art m e nt.  
C CI
C CI
C CI
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 8 0  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
T he Seri o us A d verse E ve nt Re p ort F or m ( S A E R F) s h o ul d be s u b mitte d t o  
 b y 
facsi mile ( F A X). 
•  N ort h A merica:  
 
Re p orts ca n be ma de b y tele p h o n e via t he Sa fet y H otli ne N u m ber b el o w if a S A E R F ca n n ot be 
i m me diat el y s u b mitte d. 
•  N ort h A merica:   
 
F or a n y q uesti o ns relati n g t o S A Es, ple ase c o nta ct t h e Me dical M o nit or vi a tele p h o ne:  
S A E Tele p h o ne C o nt act:  
 ( A p pe n di x I, Secti o n 1 7. 1 ) 
If o nl y li mite d i nf or mati o n is i niti all 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 ns it y or r elati 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 vail a 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 g at or be c 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 o ce d ure use d f or t he tra ns missi o n of t h e 
i niti al S A E a n d t h e sa me e ve nt ter m s h o ul d be use d.  
All S A Es s h o ul d be f oll o we d t o res ol uti o n or sta bili z ati o n.  
1 0. 1. 5  
O v er d o s e  
A n o ver d ose is defi ne d as t h e acci de nt al or i nte nti o n al a d mi nistrati o n of a n y d ose of t he pr o d uct 
t hat is c o nsi d ere d b ot h e xcessi ve a n d me di call y i m p orta nt. All o cc urre nc es of o ver d ose 
(s us pecte d or c o nfir me d a n d irr es pecti ve of w het h er or n ot it i n v ol ve d tr oril uz ole) m ust b e 
c o m m u ni cat e d t o Bi o h a ve n or a s pecifie d d esi g nee wit hi n 2 4 h o urs of t he I n vesti gat or b ec o mi n g 
a ware of t he u p date d i nf or m ati o n a n d be f ull y d oc u me nte d as 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 n a ge m e nt s h o ul d be re c or de d i ncl u di n g d etails of a n y a nti d ot e(s) 
a d mi nist ere d.  
1 0. 1. 6  
Pr e g n a n c y  
If f oll o wi n g i nitiati o n of t h e i n vesti gati o nal pr o d uct, it is s u bse q ue ntl y disc o vere d t hat a st u d y 
patie nt is pre g na nt or ma y ha v e bee n pr e g na nt at t h e ti me of t he i n v esti 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 aft er t he pr o d uct a d mi nistr ati o n, t he 
i n vesti gati o nal pr o d uct will be p er ma ne ntl y disc o nti n ue d i n a n a p pr o priat e ma n ner (i.e., d ose 
ta peri n g if nec essar y f or patie nt safet y). Pr ot o c ol-re q uire d pr oce d ur es f or t he st u d y will b e 
disc o nti n ue d a n d t he f oll o w u p m ust be p erf or me d o n t he patie nt u nless c o ntrai n dicate d b y t h e 
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 oll o w-u p pr oc e d ures s h o ul d be 
c o nsi dere d if i n dic ate d.  
Sites s h o ul d i nstr uct p ati e nts t o c o ntact t he i n vesti g at or if t he y be c o me pre g n a nt d uri n g t he 
c o urse of t he st u d y. T h e i n vesti gat or m ust i m me diatel y n otif y 
 of t he e ve nt wit hi n 2 4 h o urs 
of t he I n vesti g at or be c o mi n g a war e of t he i nf or mati o n . T he site m ust c o m plet e a Pre g na nc y 
Re p ort F or m. F oll o w u p i nf or m ati o n r e gar di n g t he c o urse of t he pre g na nc y, i ncl u di n g peri n ata l 
P P D
P P D
P P D
C CI
P P D
P P D
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 8 1  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
a n d ne o nat al o ut c o me a n d, w her e a p plica ble offs pri n g i nf or mati o n m ust  als o be re p ort e d o n a 
Pre g na nc y Re p ort F or m.  
A n y pre g na nc y t hat occ urs i n a f e male part ner of a male st u d y p arti ci pa nt s h o ul d be re p ort e d t o 
  
1 0. 1. 7  
P ot e nti al Dr u g I n d u c e d Li v er I nj ur y ( DI LI)  
W here ver p ossi bl e, ti mel y c o nfir mati o n of t h e i nitial li ver -relat e d la b orat or y a b n or m alities 
s h o ul d occ ur pri or t o t he re p orti n g of a p ot e nti al DI LI e ve nt. All o cc urre nc es of p ote ntial DI LIs, 
meeti n g t he d efi ne d criteria, m ust b e re p ort e d as S A Es as per Secti o n  1 0. 1. 4 . 
P ote ntial dr u g i n d uc e d li v er i nj ur y is defi ne d as:  
•  A mi n otra nsferases ( A T) ( A L T or A S T) el e vati o n > 3 ti mes t h e u p per li mit of n o r mal ( U L N); 
 
 
A N D  
•  T otal bilir u bi n ( T B L) > 2 ti m es U L N, wit h o ut i nitial fi n di n gs of c h olest asis  (ele v ate d ser u m 
al kali ne p h os p hatase);  
 
 
A N D  
•  
N o ot her i m m e diatel y a p pare nt p ossi bl e ca uses of A T ele v ati o n a n d h y per bilir u bi ne mia, 
i ncl u di n g b ut n ot li mite d t o, viral h e patitis, pre-e xisti n g c hr o nic or a c ute li ver dise ase, or t he 
a d mi nistr ati o n of ot her dr u g(s) k n o w n t o be  he pat ot o xic.  
If a n y p ote ntial DI LI is i de ntifie d a n d meets t he criteria a b o ve, t he Bi o h a ve n Me dic al M o nit or 
s h o ul d i m me diat el y be co nta cte d f or f urt h er i nstr ucti o n o n d osi n g a dj ust me nts a n d w het her t he 
patie nt m ust disc o nti n ue fr o m t he trial a n d a p pr o pri ate f oll o w u p re q uire m e nts.  
1 0. 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 d verse e ve nt is a n A E n ot cl assifie d as seri o us.  
1 0. 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 m ati o n s h o ul d be gi n at t he i niti ati o n of st u d y dr u g.  
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 bili zati o n, or re p orte d as 
S A Es if t he y bec o m e 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 ar e prese nt at t he e n d of st u d y 
treat me nt. 
T he f oll o wi n g la b orat or y test a b n or maliti es s h o ul d be ca pt ur e 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 ( p a per or electr o nic) as a p pr o priate:  
•  A n y la b orat or y t est res ult t hat is cli nicall y si g nifi ca nt or meets t h e defi niti o n of  a n S A E;  
C CI

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 8 2  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
•  A n y la b orat or y a b n or malit y t hat re q uir e d t he p ati e nt t o ha ve t h e st u d y dr u g disc o nti n ue d or  
i nterr u pt e d; 
•  A n y la b orat or y a b n or malit y t hat re q uir e d t he p ati e nt t o recei ve s pecific  c orr ecti ve t h era p y.  
1 1  S T A TI S TI C S  
Detail e d pla ns f or a nal ysis will be s u m mari ze d i n a se parat e Statistic al A nal ysis Pla n d oc u me nt, 
t o be writt e n a n d a p pr o v e d pri or t o data base u n bli n di n g. A s u m mar y of statistical as pects of t he 
desi g n a n d i nt e n de d a n al ysis is pr o vi de d her e  
1 1. 1  G e n er al Pr o c e d ur e s  
Cate g ori cal v aria bl es are t a b ulate d wit h c o u nts a n d p erce nt a ges. C o nti n u o us varia bles ar e 
s u m mariz e d wit h u ni v ariate statistics (e. g., n, mea n, sta n dar d err or, m e dia n, mi ni m u m a n d 
ma xi m u m).   
F or t he cal c ulati o n of descri pti ve st atistics of o bser v e d data, s u bj ects m ust h a ve a baseli ne v al ue 
t o be e val ua bl e f or e n d p oi nts base d o n v al ues a n d c h a n ges fr o m baseli ne o ver ti me. 
Ta b ulati o ns 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 bj ects wit h a n e ve nt: 
pr ot oc ol de viati o ns; n o n -st u d y me dicati o ns; ad 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 o cc urre nc es of t he sa m e e ve nt are c o u nt e d o nl y o nc e per s u bje ct.  
U nless ot her wise s pecifi e d, t he ra n d o miz ati o n p h ase a n d t he e xte nsi o n p hase will be a n al yz e d 
se paratel y. F or pati e nts recei vi n g tr oril uz ole d uri n g b ot h p hases, s u m mar y statisti cs will be 
pr o vi de d f or dat a fr o m b ot h p hases c o m bi ne d.  
1 1. 2  S a m pl e Si z e  
T he sa m pl e size f or t his st u d y will b e a p pr o xi m atel y 2 2 6 ra n d o miz e d s u bjects. T his 
acc o m m o dat es f or l ost s u bjects, a n d is base d o n t he r ati o nale t h at f oll o ws.  
Pitte n ger ( 2 0 1 5), b ase d o n a 1 2 wee k st u d y, c o n cl u d e d t hat ril uz ole pr o d uce d  a n effe ct siz e 
( C o he n’s d) of 0. 4 5 i n o ut patie nts. A n a nal ysis of t he Pitte n ger d ata f o u n d t he c orrelati o ns 
bet wee n baseli ne Y -B O C S a n d t he Y -B O C S 8, 1 0 a n d 1 2 wee ks, i n o ut patie nts, were 0. 5 0, 0. 4 5 
a n d 0. 6 8 res pecti vel y.  
Pitte n ger’s res ults are c o nsist e nt wit h t h ose fr o m  E ma mz a de hfar d’s ( 2 0 1 6) st u d y, i n w hic h 
ril uz ol e pr o d uce d a n effect size of 0. 5 9 at W ee k 1 0. Base d o n statistics prese nt e d i n t h at 2 0 1 6 
pa per, t he c orrelati o n bet wee n baseli ne a n d We e k 1 0, o n t he Y -B O C S, a p pears t o be r o u g hl y 
0. 1 8.  I n b ot h st u dies, m ore t ha n 9 0 % of t h e ra n d o mi ze d s u bjects c o m pl ete d t he st u d y.  
Ass u mi n g t hat n o m ore t ha n 1 0 % of t h e s u bjects are l ost b y Wee k 1 2 , a sa m pl e size of a b o ut 1 1 3 
per ar m will yiel d r o u g hl y 1 0 1s u bje cts per ar m. Wit h a n effect size of 0. 4 5, a t w o -si de d al p h a of 
0. 0 5, a n d a c orrelati o n of 0. 2 bet wee n b aseli n e Y -B O C S a n d Wee k 1 2  t his sa m ple siz e pr o vi des 
9 0 % p o w er t o dete ct a differe nc e bet we e n t he treat m e nt gr o u ps.  

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 8 3  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1 1. 3  P o p ul at io n s  f or A n al y si s 
T he f oll o wi n g a nal ysis sets ar e defi ne d f or t his pr ot o c ol:   
○ E nr olle d  s u bj ects: Patie nts  w h o  si g ne d a n i nf or me d c o nse nt f or m a n d were  assi g ne d  
a Patie nt I de ntific ati o n n u m ber ( PI D)  
○ Ra n d o miz e d  s u bjects: E nr olle d  s u bj ects w h o  re cei v e d a tre at m e nt assi g n m e nt fr o m t he 
I nteracti ve We b Res p o nse S yste m ( I W R S). 
○ Treat e d  s u bjects: E nr olle d  s u bjects w h o  recei ve d at  least 1  d ose  of bli n d e d st u d y 
t hera p y (tr oril u z ole or place b o) or o p e n -la b el tr oril u z ole.  
○ M o difie d I nte nt t o Tr eat ( mI T T) s u bje cts : Ra n d o miz e d s u bjects t h at re cei ve d at l east o ne 
d ose of st u d y t hera p y a n d pr o vi de d at least o n e p ost -baseli ne effica c y assess me nt  
1 1. 4  St ati sti c al M et h o d s  
1 1. 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 gr a p hic a n d b aseli n e c har act eristics are ma de f or all tr eat e d s u bjects.  A 
se parate set of ta b ulati o ns will be m a de f or s u bje cts e nr olle d b ut n ot tr eat e d. 
De m o gra p hic i nf or mati o n will be s u m marize d ( n, m ea n, S D, mi ni m u m, ma xi m u m f or 
c o nti n u o us e n d p oi nts; n a n d % f or c ate g ori cal e n d p oi nts) b y treat me nt gr o u p a n d f or all 
treat me nt gr o u ps c o m bi ne d. 
1 1. 4. 2  
Pri m ar y E n d p oi nt( s)  
As t he pri mar y o bj ecti ve of t his st u d y is base d o n t he e val uati o n of se verit y of patie nts’ 
s y m pt o m ol o g y, th e esti ma n d f or t h e  pri m ar y e n d p oi nt will be  t he eff ect d ue t o t he i nitiall y 
ra n d o miz e d tre at me nts ( w he n a d de d t o a sta n dar d of care t h era p y) if t a ke n as dir ect e d, a de j ure 
effica c y esti ma n d.  T he tar get p o p ulati o n will be t h e mI T T p o p ul ati o n.  T he pri mar y e n d p oi nt  
wil l be  th e c ha n g e fr o m baseli ne i n t he Y -B O C S t otal sc ore  tr oril uz ol e relati ve t o pla ce b o, at 
wee k 1 2 of t he ra n d o mizati o n p hase . T his tre at m e nt effect will be s u m mariz e d as t he differe n ce 
i n c ha n ge fr o m baseli ne i n t h e Y-B O C S bet wee n t he gr o u ps recei vi n g tr oril u zole  a n d plac e b o.  
Si nce t he pri mar y i nte nt of t his trial is t o e val u ate t he effect of t he dr u g w he n ta k e n as i nt e n de d 
i n t he pr ot o c ol, a h y p ot hetical strate g y will be e m pl o ye d f or t he i nterc urre nt e ve nt of 
treat me nt/st u d y disc o nti n uati o n ( d ue t o a n y r eas o n). S pecific all y, t he ass u m pti o n will b e t hat ha d 
t he s u bjects n ot disc o nti n ue d, t h eir effi cac y w o ul d h a ve bee n si mil ar t o t h e effic ac y of s u bje cts 
fr o m t he sa m e tre at me nt gr o u p w h o di d n ot disc o nti n ue. F or ot h er i nt erc urre nt e ve nts t h at d o n ot 
ca use tre at m e nt/st u d y disc o nti n uati o n s uc h as m o d est treat me nt n o n -c o m plia nc e, pr ot oc ol 
all o we d d ose a dj ust me nts, or i nitiati o n or a dj ust me nt of c o nc o mita nt me di cati o ns relat e d t o ot h er 
s y m pt o ms all o bser v e d val u es will be use d.  
T he c ha n g e fr o m baseli ne i n t he Y -B O C S t otal sc or e  will be  a n al yz e d usi n g Mi xe d M o del f or 
Re peat e d Meas ures ( M M R M) a nal ysis m o del.  T h e m o del i n cl u des tr eat me nt, visit a n d t he 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 84 of 97 
 
Draft Version 10; 13 Oct 2022 
 
treatment-by-visit interaction as fixed effects, and the baseline value of the Y-BOCS and 
baseline Y-BOCS by visit interaction as covariates. The covariance structure (SAS “R” matrix) 
will be initially specified as unstructured.  If the model fails to converge, the analyst may try a  
Huynh-Feldt structure, followed by an AR(1) structure. The troriluzole and placebo groups will 
be compared at the end of the double blind phase using a single degree of freedom contrast, with 
Kenwood-Rogers degrees of freedom, and significance assessed at a two-sided alpha level of 
0.05.  Sensitivity analyses will include, but not limited to:  multiple imputation method using a 
“jump to reference” approach and a responder analysis with response defined as a 35%, or 
greater, improvement in the Y-BOCS and with non-completers counted as failures (NC=F).  
Details of these analyses are provided in the statistical analysis plan. 
11.4.3 
Secondary Endpoint(s) 
Continuous secondary, change-from-baseline, efficacy endpoints will be analyzed using the same 
methodology as the primary endpoint.  Further details on the secondary analyses are provided in 
the SAP. 
11.4.4 
Adjustment for Multiplicity 
Type 1 error will be controlled for the primary and secondary efficacy endpoints by testing them 
with a gate-keeping procedure. The primary endpoint, change from baseline in the total Y-
BOCS, will be tested at a two-sided alpha level of 0.05. If this test is significant, then the 
secondary efficacy endpoints will be tested using Hochberg’s procedure.  If the test of the 
primary endpoint is not significant, then the unadjusted p-values for the secondary endpoints will 
be presented only for descriptive purposes, and no conclusions will be drawn from this result 
No attempt will be made to adjust for multiplicity when testing the exploratory endpoints. Any 
exploratory endpoints subjected to significance testing are evaluated at an unadjusted two-sided 
alpha level of 0.05. 
11.4.5 
Missing Data 
Both Pittenger (2015) and Emamzadehfard (2016), in studies similar to the randomized phase of 
this study, had less than 10% of the subjects fail to complete the study. Hence, we expect less 
than 10% of the subjects to be lost during the randomized phase of this study. As a sensitivity 
analysis to assess missing data assumptions of the MMRM model,  the missing data will be 
multiply imputed for the primary endpoint using a jump to reference method. Further details on 
the handling of missing data, including for the SDS, are provided in the statistical analysis plan. 
11.4.6 
Analysis of Safety 
The investigators determine the intensity of AEs and the relationship of AEs to study therapy. 
The investigators’ terms are coded and grouped by system organ class using the latest version of 
the Medical Dictionary for Regulatory Activities (MedDRA) available. AEs are presented by 
system organ class and preferred term, ordered by the overall frequency of events.  If a subject 
had an adverse event with different intensities over time, then only the greatest intensity is 
reported. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 85 of 97 
 
Draft Version 10; 13 Oct 2022 
 
AEs are tabulated in all treated subjects. SAEs occurring in subjects enrolled but not treated are 
listed. Deaths are listed for enrolled subjects without regard to onset. 
The frequencies of the following safety events are summarized by treatment regimen, and 
overall, for treated subjects:  SAEs; all AEs, nonserious AEs, AEs by intensity; AEs by 
relatedness and clinically relevant laboratory abnormalities. 
Graphical and tubular displays of on-treatment liver function test results are provided 
11.5 Schedule of Analyses 
An initial analysis of the data will be conducted after the last subject completes their Week 12 
visit.  This will include all data from the double-blind phase of the study, but will not include 
efficacy data accumulated from the extension phase.   
A final analysis of the study will be completed after the last subject completes their last study 
visit. This will summarize all efficacy data collected in the open-label phases, and summarize all 
safety, laboratory and other data collected through the entire study. 
Additional analyses may be conducted during the open-label phases of the study to support 
regulatory and administrative requirements.  
12 ETHICS AND RESPONSIBILITIES 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
Good Laboratory Practice (GLP) and all applicable regulations, including the Federal Food, 
Drug and Cosmetic Act, U.S. applicable Code of Federal Regulations (title 21), any IEC 
requirements relative to clinical studies. The study will also be conducted in compliance with the 
recommendations laid down in the most recent version of the Declaration of Helsinki, with the 
exception that registration of such Phase 1 trials in a publicly accessible database is not 
mandatory. 
This study will be conducted in compliance with the protocol. The protocol and any amendments 
and the patient informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study. 
All serious breaches must be reported to Biohaven (or designee) immediately. A Serious breach 
is a breach of the conditions and principles of GCP in connection with the study or protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
patients of the study or the scientific value of the study. 
Study personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective task(s). 
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (e.g., loss of medical licensure, debarment). 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 86 of 97 
 
Draft Version 10; 13 Oct 2022 
 
12.1 Data and Safety Monitoring Committee 
This study will not make use of a Data Safety Monitoring Committee (DMC). The study 
medication troriluzole has been tested and found to be well tolerated. Safety will be closely 
monitored via the sites and procedures for unblinding in cases of emergency will be followed. 
12.2 Institutional Review Board/Independent Ethics Committee 
The Investigators agree to provide the IEC with all appropriate documents, including a copy of 
the protocol/amendments, ICFs, advertising text (if any), Investigator’s brochure (if any) and any 
other written information provided to study subjects. The trial will not begin until the 
Investigators have obtained the IEC favorable written approvals for the above-mentioned study 
documents. A properly executed written ICF shall be read, signed, and dated by each subject 
prior to entering the trial or prior to performing any study procedure. The original signed and 
dated ICF will be kept at the Investigator site and a copy will be given to the subject. 
In the event that the protocol is amended, the revised protocol must be approved by the IEC prior 
to its implementation, unless the changes involve only logistical or administrative aspects of the 
trial. If a revised ICF is introduced during the study, each subject’s further consent must be 
obtained. The new version of the ICF must be approved by the IEC, prior to subsequently 
obtaining each subject’s consent. 
The Principal investigator and the Sponsor’s representative must sign the protocol and its 
amendments (if any) before initiating the study. 
It is the Sponsor’s responsibility to submit the protocol and its amendments (if any), and the 
ICFs to regulatory authorities when necessary. 
12.3 Informed Consent 
Investigators must ensure that patients, or, in those situations where consent cannot be given by 
patients, their legally acceptable representatives, are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they 
volunteer to participate. 
Biohaven (or designee) will provide the investigator with an appropriate (i.e., Global or e) 
sample informed consent form which will include all elements required by ICH, GCP and 
applicable regulatory requirements. The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki. 
Before the potential subject has undergone any study-related screening procedures, the nature of 
the study and the potential risks associated with it will be explained to the subject, and the 
subject will be given an opportunity to ask questions to his or her satisfaction. After the 
questions are answered, but before proceeding further, the subject must read and sign a written 
informed consent form. This signed informed consent form will be reviewed and approved by an 
IRB/IEC, revisions to the protocol and informed consent form will be reviewed and approved by 
the IRB/IEC, a copy retained in the Study Master File, and the date and time the subject signed 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 87 of 97 
 
Draft Version 10; 13 Oct 2022 
 
the form will be entered in his or her CRF. The subject will be provided with a copy of his or her 
signed and dated informed consent form. 
If informed consent is initially given by a patient’s legal guardian or legally acceptable 
representative, and the patient subsequently becomes capable of making and communicating 
their informed consent during the study, then the consent must additionally be obtained from the 
patient. 
The informed consent form must also include a statement that Biohaven and its representatives 
and regulatory authorities may have direct access to patient records. 
The rights, safety, and well-being of study patients are the most important considerations and 
should prevail over interests of science and society. 
A separate ICF will be obtained for the collection of blood for pharmacogenetic samples for 
possible future exploratory analysis investigating how genetic variation may determine  
troriluzole efficacy and safety.  All subjects will sign a pharmacogenomics ICF indicating 
whether they are consenting to or not consenting to provide a pharmacogenetic blood sample.  
All subjects will be informed that consenting to provide a blood sample for pharmacogenetic 
analysis is optional and does not affect participation in the study.  The investigator or the 
investigator’s designee is responsible for verifying the patient’s consent prior to obtaining the 
pharmacogenetic blood sample.   
The approval of the pharmacogenetic ICF may occur separately from the consent form for other 
study related procedures and assessments.  In instances were IRB approval for pharmacogenetics 
samples is not obtained, samples for genetic analysis will not be collected. 
DNA samples will be stored indefinitely from subjects who have provided written informed 
consent unless a written request for destruction of the sample is provided by the subject to the 
site which conducted the Biohaven-sponsored clinical trial.  This written request provided by the 
subject to the site requesting destruction of the subject’s pharmacogenetic samples should be 
provided by the site to the sponsor. 
12.4 Case Report Forms 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation of each study patient. Data 
reported on the CRF that are derived from source documents must be consistent with the source 
documents or the discrepancies must be explained. 
Electronic CRFs will be prepared for all data collections fields when EDC is being used. 
The confidentiality of records that could identify patients must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). 
The investigator must retain a copy of the CRFs including records of changes and corrections. If 
EDC is being used, signatures will be obtained electronically and a copy of the electronic CRFs 
will be provided (or the data from the CRFs) for future reference. 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 8 8  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1 2. 5  R e c or d s M a n a g e m e nt a n d R et e nti o n  
I n acc or da nc e wit h t h e pri nci ples of G C P a n d G L P, t he st u d y ma y be i ns pect e d b y re g ulat or y 
a ut h orities, t he S p o ns or a n d C R O. T he S p o ns or is e ntitl e d t o a ccess i nf or m ati o n a b o ut t he st at us 
of t he st u d y a n d t o r e v ie w t h e ori gi nal d oc u m e nts of t he st u d y. 
T he i n vesti gat or m ust ret ai n all st u d y rec or ds a n d s o urce d oc u m e nts f or t he ma xi m u m re q uir e d 
b y t he a p plica ble re g ul ati o ns a n d g ui deli nes, or i nstit uti o n pr oce d ur es or f or t he peri o d of ti m e 
s pecifie d b y t he s p o ns or, w hic he ver is l o n g er. T he i n vesti gat or m ust c o nt act t he S p o ns or pri or t o 
destr o yi n g a n y re c or ds ass ociate d wit h t his st u d y.  
Bi o ha ve n will n otif y t he i n v esti gat ors w he n t he st u d y files f or t his st u d y ar e n o l o n ger n ee de d.  
If t he i n vesti gat or wit h dra ws fr o m t he st u d y (i. e., retire me nt, r el oc ati o n), t h e rec or ds s hall be 
tra nsferre d t o a m ut uall y a gr ee d u p o n desi g n ee.  N oti ce of s uc h tra nsfer will be gi v e n i n writi n g 
t o Bi o ha ve n. 
It is t he res p o nsi bilit y of t he i n v esti gat or t o e ns ure t h at t he c urre nt dis p ositio n rec or d of 
i n vesti gati o nal pr o d uct (t h ose s u p plie d b y t he s p o ns or) is mai nt ai ne d at ea c h st u d y site w her e t he 
st u d y dr u g is i n ve nt ori e d a n d dis pe nse d. R ec or ds or l o gs m ust c o m pl y wit h a p pli ca bl e 
re g ulati o ns a n d g ui deli nes a n d s h o ul d i ncl u de: 
•  A m 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 b er 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 r et ur ne d fr o m eac h p ati e 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 plic a ble;  
•  A m o u nt of dr u g l ost or w aste d;  
•  A m o u nt destr o ye d at t he site if a p plic a ble;  
•  A m o u nt ret ur ne d t o s p o ns or, if a p pli ca ble;  
•  Retai n e d sa m pl es f or bi oa vaila bilit y/ bi oe q ui val e nce, i f a p pli ca bl e; 
•  Rec or d of dat es a n d i nitials of pers o n nel res p o nsi ble f or I M dis pe nsi n g a n d acc o u nta bilit y.  

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 89 of 97 
 
Draft Version 10; 13 Oct 2022 
 
12.6 Source Documentation 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent for all subjects on study. 
If source documents are created to support the collection of study information, this must be 
retained with the other pertinent medical record for each patient for verification of data points, 
unless otherwise instructed by the Sponsor or designee to enter data directly on the CRF. 
12.7 Study Files and Record Retention 
The CRO will utilize the Sponsor’s Electronic Trial Master File (eTMF) for the purposes of this 
study. The Sponsor does not require original documents that have already been scanned and 
entered into the eTMF system be forwarded to the Sponsor. Any original documents (i.e. 1572, 
signed financial disclosure, signed ICF, etc.) will be retained in the regulatory binder at the study 
site. The CRO will do a final TMF reconciliation to ensure all study files and regulatory 
documents have been correctly uploaded to the TMF prior to the close or termination of the 
study. Any materials or documents to support the clinical trial outside of the eTMF (i.e. rater 
training tapes) should be maintained by the CRO. The Sponsor will be contacted to determine 
whether the study documents/materials that are retained outside of the TMF will be forwarded to 
the Sponsor, destroyed or kept at CRO or at another facility for a longer period of time at the 
Sponsor's expense. 
13 AMENDMENTS 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Biohaven. A protocol change intended to eliminate an apparent immediate hazard 
to subjects may be implemented immediately, provided the IRB/IEC is notified within 5 days. 
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB/IEC and the investigator must await approval before 
implementing the changes. Biohaven will submit protocol amendments to the appropriate 
regulatory authorities for approval. 
If in the judgment of the IRB/IEC, the investigator, and/or Biohaven, the amendment to the 
protocol substantially changes the study design and/or increases the potential risk to the subject 
and/or has an impact on the subject's involvement as a study participant, the currently approved 
written informed consent form will require similar modification. In such cases, informed consent 
will be renewed for subjects enrolled in the study before continued participation. 
14 STUDY REPORT AND PUBLICATIONS 
Biohaven is responsible for preparing and providing the appropriate regulatory authorities with 
clinical study reports according to the applicable regulatory requirements. The publication policy 
of Biohaven is discussed in the investigator's Clinical Research Agreement. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 90 of 97 
 
Draft Version 10; 13 Oct 2022 
 
15 STUDY DISCONTINUATION 
Both Biohaven and the Principal Investigator reserve the right to terminate the study at the 
investigator’s site at any time. Should this be necessary, Biohaven or a specified designee will 
inform the appropriate regulatory authorities of the termination of the study and the reasons for 
its termination, and the Principal Investigator will inform the IRB/IEC of the same. In 
terminating the study, Biohaven and the Principal Investigator will assure that adequate 
consideration is given to the protection of the subjects’ interests. 
16 CONFIDENTIALITY 
All information generated in this study is considered highly confidential and must not be 
disclosed to any person or entity not directly involved with the study unless prior written consent 
is gained from Biohaven. However, authorized regulatory officials, IRB/IEC personnel, 
Biohaven and its authorized representatives are allowed full access to the records. 
Identification of subjects and CRFs shall be by initials, screening and treatment numbers only. If 
required, the subject's full name may be made known to an authorized regulatory agency or other 
authorized official. 
Biohaven may approve the sharing of de-identified data from this study to be made available to 
researchers for the purpose of advancing the understanding of neurologic or psychiatric illness, 
rating scales, or trial methodology for the affected population. In any publication of this data, 
confidentiality of individual subjects will be protected. 
 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 9 1  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
1 7  A P P E N DI C E S  
1 7. 1  A P P E N DI X I  - N a m e s of St u d y P er s o n n el  
 
S p o ns or:  
Bi o ha ve n P har m ace utical H ol di n g C o m pa n y Li mit e d  
c/ o Bi o ha v e n P har ma ce uticals, I nc.  
2 1 5  C h urc h Stree t 
Ne w Ha ve n,  C T  0 6 5 1 0  
 
 
Me dical M o nit or 
a n d Me dical 
M o nit or Bac k -u p:  
Bi o ha ve n P har m ace uticals, I nc.  
 
Ne w Ha ve n, C o n necti c ut 0 6 5 1 0  
 
 
Bi o ha ve n P har m ace uticals, I nc.  
 
Ne w Ha ve n, C o n necti c ut 0 6 5 1 0  
 
Cli nic al 
Researc h  
Or ga nizati o ns:  
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
C CI
P P D
P P D
P P D
P P D
P P D

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 92 of 97 
 
Draft Version 10; 13 Oct 2022 
 
17.2 APPENDIX II - Potent and Moderate Inhibitors and Inducers of the CYP1A2 
Enzyme System* 
 
CYP1A2 Potent and Moderate Inhibitors 
Amiodarone 
Artemisinin 
Atazanavir 
Cimetidine 
Ciprofloxacin 
Efavirenz 
Enoxacin 
Fluoroquinolones 
Furafylline 
Interferon 
Methoxsalen 
Mexiletine 
Mibefradil 
Tacirne 
Thiabendazole 
Ticlopidine 
Vemurafenib 
Zileuton 
 
CYP1A2 Potent and Moderate Inducers 
Barbiturates 
Beta-naphthoflavone 
Carbamazepine 
Insulin 
Methylcholanthrene 
Modafinil 
Nafcillin 
Omeprazole 
Primidone 
Rifampin 
 
*This list is not exhaustive.   
 
 
 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 93 of 97 
 
Draft Version 10; 13 Oct 2022 
 
18 REFERENCES CITED 
1. 
Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and 
comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. 
Archives of general psychiatry 2005;62:617-27. 
2. 
Ghaleiha A, Entezari N, Modabbernia A, et al. Memantine add-on in moderate to severe 
obsessive-compulsive disorder: randomized double-blind placebo-controlled study. Journal of 
psychiatric research 2013;47:175-80. 
3. 
Arabzadeh S, Shahhossenie M, Mesgarpour B, et al. L-carnosine as an adjuvant to 
fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study. 
Human psychopharmacology 2017. 
4. 
Emamzadehfard S, Kamaloo A, Paydary K, et al. Riluzole in augmentation of 
fluvoxamine for moderate to severe obsessive-compulsive disorder: Randomized, double-blind, 
placebo-controlled study. Psychiatry and clinical neurosciences 2016;70:332-41. 
5. 
Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S. 
N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: 
randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 2016;41:214-9. 
6. 
Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of 
the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder 
and major depressive disorder. Psychopharmacology 2003;167:219-20. 
7. 
Coric V, Taskiran S, Pittenger C, et al. Riluzole augmentation in treatment-resistant 
obsessive-compulsive disorder: an open-label trial. Biological Psychiatry 2005;58:424-8. 
8. 
Pittenger C, Bloch MH, Wasylink S, et al. Riluzole augmentation in treatment-refractory 
obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. The Journal of 
clinical psychiatry 2015;76:1075-84. 
9. 
Carlsson ML. On the role of cortical glutamate in obsessive-compulsive disorder and 
attention-deficit hyperactivity disorder, two phenomenologically antithetical conditions. Acta 
psychiatrica Scandinavica 2000;102:401-13. 
10. 
Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive 
disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther 2011;132:314-32. 
11. 
Jenike MA. Clinical practice. Obsessive-compulsive disorder. N Engl J Med 
2004;350:259-65. 
12. 
Pallanti S, Quercioli L. Treatment-refractory obsessive-compulsive disorder: 
methodological issues, operational definitions and therapeutic lines. Progress in neuro-
psychopharmacology & biological psychiatry 2006;30:400-12. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 94 of 97 
 
Draft Version 10; 13 Oct 2022 
 
13. 
Husted DS, Shapira NA. A review of the treatment for refractory obsessive-compulsive 
disorder: from medicine to deep brain stimulation. CNS spectrums 2004;9:833-47. 
14. 
Pallanti S, Hollander E, Goodman WK. A qualitative analysis of nonresponse: 
management of treatment-refractory obsessive-compulsive disorder. The Journal of clinical 
psychiatry 2004;65 Suppl 14:6-10. 
15. 
McDougle CJ, Fleischmann RL, Epperson CN, Wasylink S, Leckman JF, Price LH. 
Risperidone addition in fluvoxamine-refractory obsessive-compulsive disorder: three cases. The 
Journal of clinical psychiatry 1995;56:526-8. 
16. 
Saxena S, Wang D, Bystritsky A, Baxter LR, Jr. Risperidone augmentation of SRI 
treatment for refractory obsessive-compulsive disorder. The Journal of clinical psychiatry 
1996;57:303-6. 
17. 
Monaghan DT, Yao D, Cotman CW. L-[3H]Glutamate binds to kainate-, NMDA- and 
AMPA-sensitive binding sites: an autoradiographic analysis. Brain Res 1985;340:378-83. 
18. 
Egashira N, Shirakawa A, Abe M, et al. N-acetyl-L-cysteine inhibits marble-burying 
behavior in mice. Journal of pharmacological sciences 2012;119:97-101. 
19. 
Iijima M, Kurosu S, Chaki S. Effects of agents targeting glutamatergic systems on 
marble-burying behavior. Neurosci Lett 2010;471:63-5. 
20. 
Pittenger C. Glutamatergic agents for OCD and related disorders. Current treatment 
options in psychiatry 2015;2:271-83. 
21. 
Pittenger C. Glutamate modulators in the treatment of obsessive-compulsive disorder. 
Psychiatric annals 2015;45:308-15. 
22. 
Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of 
ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology 
2013;38:2475-83. 
23. 
Stewart SE, Fagerness JA, Platko J, et al. Association of the SLC1A1 glutamate 
transporter gene and obsessive-compulsive disorder. American journal of medical genetics Part 
B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric 
Genetics 2007;144B:1027-33. 
24. 
Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene 
SLC1A1 associated with obsessive-compulsive disorder. Archives of general psychiatry 
2006;63:769-76. 
25. 
Bloch MH, Wasylink S, Landeros-Weisenberger A, et al. Effects of ketamine in 
treatment-refractory obsessive-compulsive disorder. Biol Psychiatry 2012;72:964-70. 
26. 
Mattheisen M, Samuels JF, Wang Y, et al. Genome-wide association study in obsessive-
compulsive disorder: results from the OCGAS. Mol Psychiatry 2015;20:337-44. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 95 of 97 
 
Draft Version 10; 13 Oct 2022 
 
27. 
Stewart SE, Yu D, Scharf JM, et al. Genome-wide association study of obsessive-
compulsive disorder. Mol Psychiatry 2013;18:788-98. 
28. 
Naaijen J, Zwiers MP, Amiri H, et al. Fronto-Striatal Glutamate in Autism Spectrum 
Disorder and Obsessive Compulsive Disorder. Neuropsychopharmacology : official publication 
of the American College of Neuropsychopharmacology 2016. 
29. 
Baxter LR. Brain imaging as a tool in establishing a theory of brain pathology in 
obsessive compulsive disorder. J Clin Psychiatry 1990;51 Suppl:22-5; discussion 6. 
30. 
Baxter LR, Jr., Saxena S, Brody AL, et al. Brain Mediation of Obsessive-Compulsive 
Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and 
Nonhuman Primate. Semin Clin Neuropsychiatry 1996;1:32-47. 
31. 
Bolton J, Moore GJ, MacMillan S, Stewart CM, Rosenberg DR. Case study: caudate 
glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD. 
J Am Acad Child Adolesc Psychiatry 2001;40:903-6. 
32. 
Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. 
Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder 
patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 2000;39:1096-103. 
33. 
Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. 
Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive 
disorder. Neuropsychopharmacology 2009;34:2489-96. 
34. 
Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in 
OCD. Neuropsychopharmacology 2005;30:1735-40. 
35. 
Maura G, Roccatagliata E, Ulivi M, Raiteri M. Serotonin-glutamate interaction in rat 
cerebellum: involvement of 5-HT1 and 5-HT2 receptors. Eur J Pharmacol 1988;145:31-8. 
36. 
Coric V, Taskiran S, Pittenger C, et al. Riluzole augmentation in treatment-resistant 
obsessive-compulsive disorder: an open-label trial. Biol Psychiatry 2005;58:424-8. 
37. 
Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate 
antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc 
Psychopharmacol 2007;17:761-7. 
38. 
Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the 
treatment of mood and anxiety disorders. CNS Drugs 2008;22:761-86. 
39. 
Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. 
Integrating evidence from neuroimaging and neuropsychological studies of obsessive-
compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev 
2008;32:525-49. 

BHV4157-202; Clinical Protocol V10 
Confidential 
Troriluzole (BHV4157) in Adult Subjects with Obsessive Compulsive Disorder 
Page 96 of 97 
 
Draft Version 10; 13 Oct 2022 
 
40. 
Chandu BR, Nama S, Kanala K, Challa BR, Shaik RP, Khagga M. Quantitative 
estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a 
bioequivalence study. Anal Bioanal Chem 2010;398:1367-74. 
41. 
Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia: a randomized, 
double-blind, placebo-controlled pilot trial. Neurology 2010;74:839-45. 
42. 
Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar 
ataxia: a randomised, double-blind, placebo-controlled trial. The Lancet Neurology 2015;14:985-
91. 
43. 
Chandu BR, Nama S, Kanala K, Challa BR, Shaik RP, Khagga M. Quantitative 
estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a 
bioequivalence study. Analytical and Bioanalytical Chemistry 2010;398:1367-74. 
44. 
Stewart SE, Mayerfeld C, Arnold PD, et al. Meta-analysis of association between 
obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene 
SLC1A1. American journal of medical genetics Part B, Neuropsychiatric genetics : the official 
publication of the International Society of Psychiatric Genetics 2013;162B:367-79. 
45. 
Le Liboux A, Lefebvre P, Le Roux Y, et al. Single- and multiple-dose pharmacokinetics 
of riluzole in white subjects. Journal of clinical pharmacology 1997;37:820-7. 
46. 
Sheehan DV, Alphs LD, Mao L, et al. Comparative Validation of the S-STS, the ISST-
Plus, and the C-SSRS for Assessing the Suicidal Thinking and Behavior FDA 2012 Suicidality 
Categories. Innovations in clinical neuroscience 2014;11:32-46. 
47. 
Sheehan DV, Giddens JM, Sheehan IS. Status Update on the Sheehan-Suicidality 
Tracking Scale (S-STS) 2014. Innovations in clinical neuroscience 2014;11:93-140. 
 
 

B H V 4 1 5 7 -2 0 2; Cli nical Pr ot oc ol V 1 0  
C o nfi de nti al  
Tr oril uz ole ( B H V 4 1 5 7) i n A d ult S u bjects wit h O bs essi ve C o m p ulsi ve Dis or der  
Pa ge 9 7  of 9 7  
 
Draft Versi o n 1 0 ; 1 3  Oct  2 0 2 2  
 
C LI NI C A L P R O T O C O L A P P R O V A L F O R M  
Pr ot oc ol Title: A ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d trial of a dj u ncti ve tr oril uz ole i n O bs essi ve 
C o m p ulsi ve Dis or der  
 
St u d y N o: B H V 4 1 5 7 -2 0 2  
 
Draft Ori gi nal Pr ot oc ol Date: 0 9 A u g 2 0 1 7  
 
Pr ot oc ol Versi o n N o: V 1 0  
 
Pr ot oc ol Versi o n Date: 1 3  Oct  2 0 2 2  
T his st u d y pr ot oc ol was s u bje ct t o critical re vie w a n d has bee n a p pr o ve d b y t he a p pr o pri ate 
pr ot oc ol re vie w c o m mittee of t h e s p o ns or.  T he i nf or mati o n c o ntai ne d i n t his pr ot oc ol is 
c o nsiste nt wit h:  
 
- 
T he c urre nt ris k -be nefit e val uati o n of t he i n vesti g ati o nal pr o d uct.  
- 
T he m oral, et hical a n d scie ntifi c pri nci ples g o ver ni n g cli ni cal r esearc h as set o ut i n t h e 
Declarati o n of H elsi n ki, a n d pri nci ples of G C P as descri be d i n 2 1 C F R parts 5 0, 5 4, 5 6 
a n d 3 1 2 a n d ac c or di n g t o a p plic a ble l ocal re q uir e me nts.  
- 
T he I n vesti g at or will be s u p pli e d wit h details of a n y si g nifica nt or ne w fi n di n gs, 
i ncl u di n g a d verse e v e nts, relati n g t o treat me nt wit h t he i n vesti g ati o n al pr o d uct. 
 
 
N a m e a n d Title  
Si g n at ure A p pr o v al  
D ate  
A ut h or/ Pr ot oc ol Writer:  
 
 
Bi o ha ve n P har mace uticals  
(I c o nfir m, Q C c o m plete d f or re q uire d ele me nts) 
 
 
Cli nical O perati o ns:  
  
 
  
Bi o ha ve n P har mace uticals  
 
 
Bi ostatistics:  
 
 
 
Bi o ha ve n P har mace uticals  
 
 
M e dical Lea d:  
  
 
 
 
Bi o ha ve n P har mace uticals  
 
 
R e g ulat or y Affairs:  
 
 
 
 
 
Bi o ha ve n  P har mace uticals  
 
 
P P D
P P D
P P D
P P D P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D