A Phase 2, Double Blind, Placebo-Controlled Study to Explore the Safety, Tolerability, and Activity of SXC-2023 in Adults With Moderate to Severe Trichotillomania (TTM) When Dosed for 6 Weeks
Phase: PHASE2
Conditions: Trichotillomania
Sponsor: Promentis Pharmaceuticals, Inc.

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CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
 
 
 
 
CLINICAL PROTOCOL 
 
 
A Phase 2, Double Blind, Placebo-Controlled Study to Explore the Safety, Tolerability, 
and Activity of SXC-2023 in Adults with Moderate to Severe Trichotillomania (TTM) 
When Dosed for 6 Weeks 
 
 
 
Protocol No.: 
PRO-201 
US IND No.: 
133689 
 
Amendment 3: 
25 June 2019 
 
 
Previous versions 
 
Amendment 2: 
01 May 2019 
 
Amendment 1: 
02 November 2018 
 
Original Protocol Date: 
16 August 2018 
 
 
GCP Statement 
 
This study is to be performed in full compliance with the protocol, Good Clinical Practices 
(GCP), and applicable regulatory requirements. All required study documentation will be 
archived as required by regulatory authorities. 
 
Confidentiality Statement 
 
This document is confidential. It contains proprietary information of Promentis 
Pharmaceuticals, Inc. Any viewing or disclosure of such information that is not authorized 
in writing by Promentis Pharmaceuticals, Inc. is strictly prohibited. Such information may 
be used solely for the purpose of reviewing or performing this study. 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
Page 2 
CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
 
 
PROTOCOL REVISION HISTORY 
 
Date/Name 
Description 
17 June 2019/ Amendment 
3 
• 
Study procedures were updated with administration of the C-SSRS 
since last visit version at subject’s Day 1 and Week 8 visits. 
• 
Inclusion criteria #8 was updated to clarify contraceptive 
requirements. 
• 
First page: Administrative change, protocol amendment 2 date of 
finalization changed from 16 April to 01 May 
• 
Study procedures updated to clarify that pregnancy tests will only 
be performed for female subjects without confirmation of sterility. 
• 
Updates to MAD (PRO-104) study information (safety and PK). 
01 May 2019/ 
Amendment 2 
• 
The screening period for subjects was expanded from up to 30 days 
to up to 40 days. 
• 
Inclusion criterion 4 was updated to clarify that stimulants are not 
allowed and that certain over-the-counter/herbal psychoactive drugs 
are allowable with medical monitor approval. The requirement for 
subjects to not use any of the listed medications has been changed 
from 30 days prior to screening, to 30 days prior to first dose. 
• 
Inclusion criterion 5 timeline for N-Acetylcysteine changed from at 
least 90 days prior to first screening to at least 90 days prior to first 
dose. 
• 
Inclusion criterion 8 was updated to elaborate on requirements for 
contraception for females of childbearing potential. 
• 
Exclusion criterion 2 was updated to prohibit CBT for TTM, or other 
body-focused repetitive behavior or any obsessive compulsive related 
or impulse control disorder any time from within 30 days prior to first 
screening to within 60 days prior to first dose. For other 
psychotherapies, changed from a minimum of 4 weeks at time of first 
screening to a minimum of 60 days at time of first dose. 
• 
Exclusion criterion 3 was updated to prohibit other behavioral 
interventions for TTM for 60 days prior to first dosing. 
• 
An exclusionary criterion was added for laboratory evidence of renal 
impairment. 
• 
Section 6.2.3.3 was updated to add melatonin as a disallowed 
treatment within 24 hours prior to any study visits. 
• 
The Safety and PK sections for the 104 MAD study were updated 
with final data. 
• 
Change in Figure 1 (Diagram of study design) and Appendix A, 
Schedule of Assessments to reflect integration of 7 day run-in as part 
of screening. Screening period reflects now reflects Day -40 to Day 
0. 
• 
Added Section 9.8 Medication errors requirements. 
• 
Clarification made in overdose section. 
• 
Protocol Violation changed to Protocol Deviation. 
• 
Minimal administrative changes throughout. 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
02 November 
2018/Amendment 1 
• 
The protocol has been revised to provide additional information on 
the nonclinical studies (e.g., 90-day toxicity data were added) as well 
as additional information on the safety and pharmacokinetic findings 
in the multiple ascending dose study and the single ascending dose 
study. 
• 
The title of the protocol has been updated and the Phase has been 
modified from Phase 2A to Phase 2. 
• 
The fax number and email address for the pharmacovigilance team 
were added for purposes of safety reporting. 
• 
The protocol was modified to indicate that the 7-day 
Trichotillomania Symptom Diary baseline period could be 
performed at any time during the screening window. 
• 
The protocol was modified to indicate that the CGI-S/C 
will be performed using the iPad device and training for 
the PGI-S/C and CGI-S/C software was added. 
• 
An electrocardiogram assessment was added at the 
end of the treatment period. 
• 
Clarifications were made to the eligibility criteria, including 
the exclusion of subjects using wearable devices or other 
behavioral self- help strategies. 
• 
Restrictions on alcohol and cannabinoid use were added. 
• 
Instructions indicating that the screening assessments may 
occur over multiple visits were added and instructions 
regarding a 10-day extension of the screening window were 
added. 
• 
Clarification was added regarding the criteria for 
repeating the baseline 7-day Trichotillomania Symptom 
Diary period. 
• 
Details regarding the study drug supplies and 
study drug administration were added. 
• 
The statistical section was updated to provide additional 
details on the sample size estimation and the planned 
analyses. 
• 
Additional details were added regarding the number of missed 
doses and diary non-compliance that are permitted before a 
subject would be removed from the Per Protocol Population. 
Missed doses and diary non-compliance were added as 
separate reasons for discontinuation. 
• 
Additional instructions were added regarding dose suspensions. 
• 
Clarification was added regarding the recording of adverse 
events during screening (pre-dose Day 1). 
• 
Clarification was made that a urine drug test is not required 
at Week 3 and Week 6 and the components of the test were 
modified. 
• 
The protocol was modified to indicate that re-confirmation of 
eligibility through assessment of changes in medical and 
psychiatric history and concomitant medications would be 
performed at Day 1. 
• 
Clarification was added that the subject does not have be 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
in the supine position for at least 5 minutes prior to 
respiratory rate and temperature assessments. 
• 
Instructions for the early termination visit were updated. 
• 
Uric acid was added as a clinical laboratory assessment. 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
Page 5 
CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES 
 
A Phase 2, Double Blind, Placebo-Controlled Study to Explore the Safety, Tolerability, 
and Activity of SXC-2023 in Adults with Moderate to Severe Trichotillomania (TTM) 
When Dosed for 6 Weeks 
 
 
 
 
SPONSOR: 
Promentis Pharmaceuticals, Inc. 
826 North Plankinton Avenue, Suite 400 
Milwaukee, Wisconsin 53203, USA 
SPONSOR’S 
REPRESENTATIVE: 
Patricia P. Cotter 
Senior Director, Head of Clinical 
Operations 
Tel.: +1 617 300 6172 
E-Mail: pcotter@promentispharma.com 
26 Jun 2019 
Signature 
Date 
PRINCIPAL INVESTIGATOR 
AND CLINICAL SITE: 
Signature 
Date 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
Page 6 
CONFIDENTIAL 
PRO-201_Protocol_25 Jun 2019 
 
 
 
ADDITIONAL KEY CONTACTS FOR THE STUDY 
Sponsor Representative 
Patricia P. Cotter 
Senior Director, Head of Clinical Operations 
Tel.: +1 617 300 6172 
E-Mail: pcotter@promentispharma.com 
Sponsor Representative 
(Back up) 
Chad E. Beyer, PhD, MBA 
Senior Vice President, Research and 
Development 
Tel.: +1 267 614 4645 
E-Mail: cbeyer@promentispharma.com 
Sponsor Medical Officer 
Thomas Beck, MD 
Chief Medical Officer, Promentis 
Tel: +617 231 2403 
E-Mail: tbeck@fprimecapital.com 
Medical Monitor 
Robert Leadbetter, MD 
Medical Director, Syneos Health 
Tel.: +1 919 601 2502 
E-Mail: robert.leadbetter@syneoshealth.com 
Safety Monitoring 
(Pharmacovigilance) 
Syneos Health Safety 
Fax: +1 877 464 7787 
Email: safetyreporting@syneoshealth.com 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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TABLE OF CONTENTS 
PROTOCOL REVISION HISTORY .............................................................................. 2 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES .......................... 5 
ADDITIONAL KEY CONTACTS FOR THE STUDY ................................................. 6 
TABLE OF CONTENTS .................................................................................................. 7 
TABLE OF FIGURES ..................................................................................................... 10 
TABLE OF TABLES ....................................................................................................... 10 
1 
SYNOPSIS ................................................................................................................. 11 
2 
ABBREVIATIONS ................................................................................................... 17 
3 
BACKGROUND AND RATIONALE .................................................................... 20 
3.1 
Background .......................................................................................................... 20 
3.1.1 
Preclinical Trials ............................................................................................ 20 
3.1.1.1 
Pharmacology ........................................................................................... 20 
3.1.1.2 
Pharmacokinetics ..................................................................................... 21 
3.1.1.3 
Toxicity...................................................................................................... 21 
3.1.2 
Effects of SXC-2023 in Humans ................................................................... 23 
3.1.2.1 
Safety ......................................................................................................... 24 
3.1.2.2 
Pharmacokinetics and Product Metabolism ......................................... 25 
3.2 
Rationale ............................................................................................................... 26 
3.2.1 
Rationale for this Study and Study Design .................................................. 26 
3.2.2 
Rationale for Dose Selection .......................................................................... 27 
3.3 
Risks and/or Benefits to Subjects ....................................................................... 27 
4 
STUDY OBJECTIVES ............................................................................................ 28 
4.1 
Primary Objective ................................................................................................ 28 
4.2 
Secondary Objectives........................................................................................... 28 
4.3 
Exploratory Objectives ........................................................................................ 28 
5 
INVESTIGATIONAL PLAN .................................................................................. 28 
5.1 
Overall Study Design and Plan ........................................................................... 28 
5.2 
Study Duration ..................................................................................................... 31 
5.3 
Study Conduct ...................................................................................................... 31 
6 
STUDY POPULATION ........................................................................................... 31 
6.1 
Number of Subjects .............................................................................................. 31 
6.2 
Eligibility Criteria ................................................................................................ 31 
6.2.1 
Inclusion Criteria ........................................................................................... 31 
6.2.2 
Exclusion Criteria .......................................................................................... 33 
6.2.3 
Restrictions ..................................................................................................... 35 
6.2.3.1 
Cognitive Behavioral Therapy or Other Behavioral Interventions .... 35 
6.2.3.2 
Prior/Concomitant Medications ............................................................. 35 
6.2.3.3 
Alcohol, Cannabinoids and Melatonin ................................................... 36 
6.2.3.4 
Contraceptive Requirements .................................................................. 36 
7 
STUDY PROCEDURES .......................................................................................... 37 
7.1 
Screening Visit (Day −40 to Day 0) ..................................................................... 37 
7.1.1 
Screen Failures ............................................................................................... 38 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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7.1.2 
Extension to the Screening Window ............................................................. 38 
7.1.3 
Re-screening ................................................................................................... 38 
7.2 
Day 1 ...................................................................................................................... 38 
7.3 
Week 3 (Day 21 [±4 days]) ................................................................................... 40 
7.4 
Week 6 (Day 42 [±4 days])/Early Termination Visit ........................................ 40 
7.5 
Follow-up (Day 56 [±4 days]) .............................................................................. 41 
7.6 
Unscheduled Visit................................................................................................. 42 
7.7 
Early Withdrawal ................................................................................................ 42 
7.8 
Discontinuation of the Study ............................................................................... 43 
8 
CRITERIA FOR EVALUATION ........................................................................... 43 
8.1 
Safety Evaluation ................................................................................................. 43 
8.1.1 
Medical History, Demographic and Other Baseline Information ............. 43 
8.1.2 
Physical Examination .................................................................................... 44 
8.1.3 
Vital Signs ....................................................................................................... 44 
8.1.4 
12-Lead Electrocardiograms ......................................................................... 44 
8.1.5 
Clinical Laboratory Tests .............................................................................. 45 
8.1.6 
Adverse Events ............................................................................................... 46 
8.1.7 
Prior and Concomitant Medications ............................................................ 46 
8.1.8 
Columbia-Suicide Severity Rating Scale ...................................................... 46 
8.2 
Neurocognitive and Other Behavioral Measurements ..................................... 47 
8.2.1 
Mini-International Neuropsychiatric Interview, version 7.0.2 with 
Trichotillomania and Body Dysmorphic Disorder Modules ...................... 47 
8.2.2 
Barratt Impulsiveness Scale .......................................................................... 47 
8.2.3 
Cambridge Neuropsychological Test Automated Battery .......................... 47 
8.2.4 
Massachusetts General Hospital Hairpulling Scale .................................... 47 
8.2.5 
Patient Global Impression of Status/Change ............................................... 47 
8.2.6 
Clinical Global Impression of Severity/Change .......................................... 48 
8.2.7 
Milwaukee Inventory of Subtypes of Trichotillomania – Adult 
Version ............................................................................................................ 48 
8.2.8 
Trichotillomania Symptom Diary ................................................................. 48 
8.3 
Glutathione Blood Collection .............................................................................. 49 
9 
TEST ARTICLE AND ADMINISTRATION ........................................................ 49 
9.1 
Test Article Identification, Supply, Packaging, Labeling, and Storage .......... 49 
9.2 
Study Drug Administration ................................................................................ 49 
9.3 
Study Drug Accountability and Destruction ..................................................... 49 
9.4 
Blinding ................................................................................................................. 50 
9.5 
Randomization ..................................................................................................... 50 
9.6 
Missed Doses ......................................................................................................... 50 
9.7 
Dose Suspension ................................................................................................... 50 
9.8 
Medication Errors ................................................................................................ 51 
9.9 
Treatment of Overdose ........................................................................................ 51 
10 ADVERSE EVENTS ................................................................................................ 51 
10.1 
Definition .............................................................................................................. 52 
10.2 
Severity Scale for Adverse Events ...................................................................... 52 
10.3 
Relationship to Study Drug ................................................................................. 52 
10.4 
Reporting Adverse Events ................................................................................... 53 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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10.5 
Serious Adverse Events ....................................................................................... 53 
10.5.1 
Definition ........................................................................................................ 53 
10.5.2 
Initial Reporting ............................................................................................. 54 
10.5.3 
Follow-up ........................................................................................................ 54 
10.6 
Pregnancy ............................................................................................................. 54 
11 STUDY ADMINISTRATION ................................................................................. 55 
11.1 
Ethics ..................................................................................................................... 55 
11.1.1 
Institutional/Independent Review Board ..................................................... 55 
11.1.2 
Ethical Conduct of the Study ........................................................................ 55 
11.1.3 
Subject Information and Consent ................................................................ 55 
11.2 
Termination of the Study .................................................................................... 56 
11.3 
Data Quality Assurance ....................................................................................... 56 
11.4 
Direct Access to Source Data/Documents .......................................................... 56 
11.5 
Data Handling and Record Keeping .................................................................. 56 
11.6 
Report Format ...................................................................................................... 56 
11.7 
Publication Policy ................................................................................................. 57 
12 STATISTICAL METHODS .................................................................................... 57 
12.1 
Determination of Sample Size ............................................................................. 57 
12.2 
Analysis Populations ............................................................................................ 57 
12.3 
Statistical Analysis ............................................................................................... 58 
12.3.1 
Subject Disposition......................................................................................... 58 
12.3.2 
Protocol Deviations ........................................................................................ 58 
12.3.3 
Demographics and Baseline Characteristics ............................................... 58 
12.3.4 
Safety Analysis ............................................................................................... 58 
12.3.4.1 
Adverse Events ......................................................................................... 58 
12.3.4.2 
Other Safety Assessments ........................................................................ 59 
12.3.4.3 
Concomitant Medications ....................................................................... 59 
12.3.5 
Analysis of Neurocognitive and Other Behavioral Measurements ............ 59 
12.3.6 
Analysis of Glutathione Concentrations ...................................................... 59 
13 REFERENCES ......................................................................................................... 60 
APPENDIX A SCHEDULE OF EVENTS ..................................................................... 63 
APPENDIX B BASIC ELEMENTS OF INFORMED CONSENT ............................. 65 
APPENDIX C SUMMARY OF BLOOD DRAW VOLUMES .................................... 67 
APPENDIX D TRICHOTILLOMANIA SYMPTOM DIARY ................................... 68 
APPENDIX E BARRATT IMPULSIVENESS SCALE ............................................... 69 
APPENDIX F CAMBRIDGE NEUROPSYCHOLOGICAL TEST 
AUTOMATED BATTERY ...................................................................................... 70 
APPENDIX G MASSACHUSETTS GENERAL HOSPITAL HAIRPULLING 
SCALE ....................................................................................................................... 77 
APPENDIX H MILWAUKEE INVENTORY OF SUBTYPES OF 
TRICHOTILLOMANIA – ADULT VERSION .................................................... 79 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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PRO-201_Protocol_25 Jun 2019 
 
 
TABLE OF FIGURES 
Figure 1 
Diagram of Study Design ......................................................................... 31 
 
 
TABLE OF TABLES 
Table 1 
Reasons for Discontinuation ................................................................... 42 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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1 SYNOPSIS 
 
Compound No. 
SXC-2023 – a novel small molecule activator of the cystine-glutamate antiporter (System xc- or 
Sxc) 
Study Protocol Title 
A Phase 2, Double Blind, Placebo-Controlled Study to Explore the Safety, Tolerability, and 
Activity of SXC-2023 in Adults with Moderate to Severe Trichotillomania (TTM) When Dosed 
for 6 Weeks 
Sites 
Up to 15 sites in the United States 
Phase of Development 
Phase 2 
Dosage and Administration 
Double-blinded study drug: 
• 
SXC-2023 50 mg once daily (QD) 
• 
SXC-2023 200 mg QD 
• 
SXC-2023 800 mg QD 
• 
Placebo QD 
SXC-2023 supplied as 50 mg and 200 mg capsules. Matching placebo capsules will be used for 
blinding. 
Primary Objective 
• 
To explore the safety and tolerability of SXC-2023 in adults with TTM when dosed for a 
period of 6 weeks. 
Secondary Objectives 
• 
To explore the activity of SXC-2023 in subjects with moderate to severe TTM when 
dosed for a period of 6 weeks using assessments of TTM disease activity (e.g., 
Trichotillomania Symptom Diary [TSD], Massachusetts General Hospital Hairpulling 
Scale [MGH-HPS], Clinical Global Impression of Severity and Change [CGI-S/CGI-C], 
and Patient Global Impression of Status and Change [PGI-S/PGI-C]). 
• 
To provide preliminary psychometric evidence of the reliability, validity, and 
responsiveness of the newly developed TSD assessment. 
Exploratory Objectives 
• 
To test the activity of SXC-2023 on neurocognitive assessments (e.g., Stop Signal Task 
[SST], Cambridge Gambling Task [CGT] and other behavioral measures including 
Reaction Time [RTI], Paired Associates Learning [PAL], and Milwaukee Inventory of 
Subtypes of TTM - Adult Version [MIST-A]). 
• 
To test the effects of SXC-2023 on whole blood glutathione levels. 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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PRO-201_Protocol_25 Jun 2019 
 
 
 
Study Design 
This study is a randomized, double blind, placebo-controlled, multicenter study to evaluate the 
safety, tolerability, and activity of SXC-2023 (50 mg, 200 mg, or 800 mg QD) when dosed for 6 
weeks compared to placebo in adult subjects diagnosed with moderate to severe TTM. Subjects will 
be screened and will perform required assessments for eligibility during a 40-day screening period. 
During the screening period, subjects will be trained on site on how to use an electronic Patient 
Report Outcome (ePRO) handheld device to complete the TSD. After all screening assessments are 
complete, the subjects will complete the TSD at home every evening for 7 consecutive days 
during the screening period. 
On Study Day 1, eligible subjects will complete protocol-specified assessments and study 
procedures, including neurocognitive and other assessments, and will be assigned to receive one of 
three doses of SXC-2023 or matching placebo. Subjects will be assigned to treatment groups using 
a randomization scheme including a stratification factor for whether subjects are currently taking 
concomitant selective serotonin re-uptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake 
inhibitors (SNRIs). Subjects will be instructed to complete the TSD on their ePRO handheld device 
every 24 hours (just prior to bedtime) during the 6-week treatment period. Subjects will be 
instructed to take their study medication at approximately the same time each day (preferably in the 
morning at least 1 hour prior to or 2 hours after a meal). Subjects will return to the site to complete 
assessments at Week 3 (±4 days) and Week 6 (±4 days). Subjects will then return for follow-up at 
Week 8 (±4 days). 
Neurocognitive and other behavioral measurements (in addition to daily TSD completion) will 
include the following: 
Screening (neurocognitive and other behavioral measurements must be performed at one visit): 
• 
Mini-International Neuropsychiatric Interview (MINI) version 7.0.2 with 
Trichotillomania and Body Dysmorphic Disorder modules (MINI-TTM) 
• 
Training on the Cambridge Neuropsychological Test Automated Battery (CANTAB) iPad 
device which will be used for the SST, CGT, RTI, and PAL 
• 
Training on the TSD on the ePRO handheld device. Once trained, subject to complete the 
TSD on their ePRO handheld device every 24 hours for 7 days at home. 
• 
Training on the PGI-S, PGI-C, CGI-S, and CGI-C software using the iPad device 
• 
Barratt Impulsiveness Scale (BIS) 
• 
MGH-HPS 
• 
Columbia Suicide Severity Rating Scale (C-SSRS) 
Day 1 (Baseline): 
• 
SST, CGT, RTI, and PAL (completed using the CANTAB iPad device) 
• 
MGH-HPS 
• 
PGI-S (completed using an iPad device) 
• 
CGI-S (completed using an iPad device) 
• 
C-SSRS 
• 
MIST-A 
Week 3 (±4 days): 
• 
MGH-HPS 
• 
PGI-S and PGI-C (completed using an iPad device) 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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• 
CGI-S and CGI-C (completed using an iPad device) 
• 
MIST-A 
• 
C-SSRS 
Week 6 (±4 days): 
• 
SST, CGT, RTI, and PAL (completed using the CANTAB iPad device) 
• 
MGH-HPS 
• 
PGI-S and PGI-C (completed using an iPad device)) 
• 
CGI-S and CGI-C (completed using an iPad device) 
• 
MIST-A 
• 
C-SSRS 
Follow up/ET, Week 8 (±4 days): 
• 
C-SSRS 
Safety will be evaluated via reports of adverse events (AEs), clinical laboratory tests, physical 
examinations, vital signs, the C-SSRS, electrocardiograms (ECGs), and concomitant treatments. 
Evaluation of AEs will include assessment of changes in psychiatric symptoms, including 
changes in emotions, cognition, or behavior, to determine whether changes are clinically 
significant (e.g., onset or exacerbation of depressed mood) and possibly related to study drug. 
Whole blood samples for glutathione measurements will be taken at baseline (prior to dosing) and 
at Week 6 (±4 days). 
Study Duration 
Subjects will be dosed for 38 to 46 consecutive days. The maximum anticipated subject 
participation will be approximately 100 days (40 days for the screening period, 6 weeks of 
treatment, and a follow-up visit on Day 60 at the latest). One 10-day extension of the 
screening period may be permitted on a case-by-case basis with medical monitor or designee 
approval (e.g., if needed for adequate drug washout or additional ePRO training). 
Number of Subjects (Planned) 
Approximately 120 subjects are planned to be enrolled so that 100 subjects complete the study. In 
the event that a subject leaves the study (e.g., voluntarily withdraws, discontinues due to an AE, is 
lost to follow-up) prior to completing study procedures and assessments at the Week 3 visit, an 
additional subject may be randomized. Subjects who leave the study after the Week 3 visit but 
before study completion will be considered as part of the final enrollment sample of 120 subjects. 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for the study: 
1. Adult, female or male, 18-45 years of age, inclusive at screening. 
2. Has provided signed written informed consent with willingness and ability to comply 
with all aspects of the protocol. 
3. Diagnosis of current TTM based on Diagnostic and Statistical Manual of Mental 
Disorders, fifth edition (DSM-5) criteria and confirmed using the clinician-administered 
MINI-TTM. In addition, subjects should: 
a. Have a history of TTM for at least one year 
b. Have a history of daily hair pulling for at least 6 months prior to the first dose 

Phase 2 Study Protocol 
Promentis Pharmaceuticals, Inc. 
Protocol No.: PRO-201 
US IND No.: 133689 
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4. Except for SSRIs and SNRIs, has not used any psychoactive medications including, but 
not limited to, other antidepressants, anxiolytics, mood stabilizers, anti-psychotics, 
benzodiazepines, stimulants, sulfasalazine, and St. John’s Wort 30 days prior to first dose. 
Subjects will be allowed to maintain background therapy with SSRIs or SNRIs if on 
stable regimen for a minimum of 90 days prior to first dose and there are no anticipated 
changes to the SSRI/SNRI during course of trial. Please refer to Section 6.2.3.2. 
a. Certain over-the-counter/herbal psychoactive drugs may be allowable with 
medical monitor approval (e.g., melatonin). 
5. Has not used N-acetylcysteine for at least 90 days prior to the first dose. 
6. Has not used gemfibrozil or repaglinide for 1 week prior to the first screening visit. 
7. Medically healthy with no clinically significant findings in medical history, physical 
examination, laboratory profiles, vital signs, or ECGs, as deemed by the Principal 
Investigator (PI) or designee. 
8. For a female of childbearing potential: either be sexually inactive (abstinent as a life 
style) for 28 days prior to the first dosing and throughout the study or be using one of the 
following acceptable birth control options: 
• 
Oral contraception for at least 3 months prior to the first dosing along with either a 
physical (e.g., condom, diaphragm) or a chemical (e.g., spermicide) barrier method 
from the time of screening and throughout the study 
• 
IUD (either hormone-releasing or non-hormone releasing) for at least minimum 
duration per current labeling along with either a physical (e.g., condom, diaphragm) 
or a chemical (e.g., spermicide) barrier method from the time of screening and 
throughout the study 
• 
Depo contraception for at least minimum duration per current labeling prior to the 
first dosing along with either a physical (e.g., condom, diaphragm) or a chemical 
(e.g., spermicide) barrier method from the time of screening and throughout the study 
• 
Double physical barrier method (e.g., condom and diaphragm) from 14 days prior to 
the first dose and throughout the study 
• 
Physical plus chemical barrier method (e.g., condom with spermicide) from 14 days 
prior to the first dose and throughout the study 
In addition, female subjects of childbearing potential will be advised to remain sexually 
inactive or to keep the same birth control method for at least 30 days following the last dose. 
9. Female of non-childbearing potential: must have undergone one of the following 
sterilization procedures, at least 6 months prior to the first dose: 
• 
hysteroscopic sterilization; 
• 
bilateral tubal ligation or bilateral salpingectomy; 
• 
hysterectomy; 
• 
bilateral oophorectomy; 
Or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serum 
follicle stimulating hormone levels consistent with postmenopausal status or have medically 
documented history of biological or congenital sterility. 
10. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain 
from sexual intercourse during the study until 30 days beyond the last dose of study 

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drug/placebo. (No restrictions are required for a vasectomized male provided his 
vasectomy has been performed 4 months or more prior to the first dose of study 
drug/placebo. No restrictions are required for males with a medically documented history 
of biological or congenital sterility. A male who has been vasectomized less than 
4 months prior to the first dose of study drug must follow the same restrictions as a 
non-vasectomized male). 
11. If male, must agree not to donate sperm from the first dose until 30 days after the last 
dose administration. 
12. Must be able to fluently read and write in English. 
13. Understands the study procedures in the informed consent form (ICF) and is willing and 
able to comply with the protocol. 
Exclusion Criteria 
Subjects meeting ANY of the following criteria must NOT be enrolled in this study. 
1. Females who are pregnant or breastfeeding or intend to become pregnant during the study 
period or within 30 days of the final dose of study drug. 
2. Subjects engaged in cognitive behavioral therapy (CBT) for TTM or other body-focused 
repetitive behavior or any obsessive-compulsive related or impulse control disorder any 
time within 60 days prior to first dose. For other psychotherapies, subject must have been 
engaged in that psychotherapy for a minimum of 60 days at the time of first dose and 
must be willing to maintain the same frequency and type of therapy for the duration of the 
study period. 
3. Subjects who have initiated any other behavioral interventions (e.g., wearable devices, 
behavioral self-help strategies) within 60 days prior to first dose. 
4. Subject is mentally or legally incompetent. 
5. Subject suffered a concussion in the past 6 months prior to screening. Any history of 
traumatic brain injury with loss of consciousness in the year prior to first screening visit. 
6. Any lifetime history of any psychotic disorder, including schizophrenia, or any bipolar or 
bipolar-related disorder as determined by clinical history or confirmed at screening with 
the MINI, version 7.0.2. 
7. Current major depressive episode confirmed at screening with the MINI, version 7.0.2. 
8. Per PI judgment, the presence of any emotional problems or psychiatric disorders that 
may obscure evaluation of TTM or pose a risk to subject safety or stability during the 
study period. Other emotional problems or diagnoses may include, but are not limited 
to, other body-focused repetitive behaviors, post-traumatic stress disorder, obsessive- 
compulsive disorder, panic disorder, compulsive gambling, borderline personality 
disorder, or antisocial personality disorder. 
9. History of any injury, illness, or condition that, in the opinion of the PI or designee, might 
confound the results of the study or poses an additional risk to the subject by their 
participation in the study. 
10. Laboratory evidence of renal impairment (e.g, a calculated creatinine clearance of < 80) 
11. Presence of any substance use disorder or, in the opinion of the PI or designee, 
problematic substance use (excluding nicotine or caffeine) within the 2 years prior to 
screening. 
12. History of seizure disorder with the exception of subjects who have been off anti-seizure 
medication and have not had a seizure in the past 5 years. 
13. Subjects with any of the following: 
a. Any psychiatric hospitalizations in the past year, 

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b. Imminent risk of suicide based on PI’s or designee’s clinical judgment or 
psychiatric examination 
c. Active suicidal ideation in the past 6 months as evidenced by positive 
endorsement to Item 4 or 5 on the C-SSRS, 
OR 
d. Any history of suicidal behavior in the past year as evidenced by positive 
endorsement to any of the suicidal behavior items on the C-SSRS. 
14. Has previously participated in any Promentis Phase 1 study. 
15. Participation in another interventional clinical study (including CBT or other behavioral 
intervention) within 30 days prior to the first screening visit. The 30-day window will be 
derived from the date of the last blood collection or dosing, whichever is later, in the 
previous study to the date of initiation of screening in the current study. 

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2 ABBREVIATIONS 
 
AE 
Adverse event 
AUC 
Area under the concentration-time curve 
BID 
Twice daily 
BIS 
Barratt Impulsiveness Scale 
BP 
Blood pressure 
CANTAB 
Cambridge Neuropsychological Test Automated Battery 
CBT 
Cognitive behavioral therapy 
CFR 
Code of Federal Regulations 
CGI-C 
Clinical Global Impression of Change 
CGI-S 
Clinical Global Impression of Severity 
CGT 
Cambridge Gambling Task 
Cmax 
Maximum observed concentration 
CNS 
Central nervous system 
CRF/eCRF 
Case report form/electronic case report form 
CRO 
Contract research organization 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DG 
Days of gestation 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, fifth edition 
ECG 
Electrocardiogram 
EE2 
Ethinyl estradiol 
ePRO 
electronic Patient Reported Outcome 
FE 
Food effect 
GCP 
Good Clinical Practice(s) 
GLP 
Good Laboratory Practice 
HR 
Heart rate 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IND 
Investigational New Drug 
IRB 
Institutional/independent review board 
Kg 
Kilogram 
m2 
Meters squared 

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MAD 
Multiple ascending dose 
MedDRA® 
Medical Dictionary for Regulatory Activities® 
Mg 
Milligram 
MGH-HPS 
Massachusetts General Hospital Hairpulling Scale 
MINI 
Mini-International Neuropsychiatric Interview, version 7.0.2 
MINI-TTM 
Mini-International Neuropsychiatric Interview, version 7.0.2 with 
Trichotillomania and Body Dysmorphic Disorder modules 
MIST-A 
Milwaukee Inventory of Subtypes of TTM – Adult version 
mL 
Milliliter 
mmHg 
Millimeter of mercury 
NAC 
N-acetylcysteine 
NET 
Norethindrone 
Ng 
Nanogram 
No. 
Number 
NOAEL 
No observed adverse effect level 
OC/DDI 
Oral contraceptive/drug-drug interaction study 
OTC 
Over-the-counter 
PAL 
Paired Associates Learning 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Status 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PP 
Per Protocol 
PT 
Preferred term 
QA 
Quality assurance 
QD 
Once daily 
QTc 
Corrected QT 
QTcF 
QT corrected by Fridericia’s formula 
RR 
Respiratory rate 
RTI 
Reaction Time 
SAD 
Single ascending dose 
SAE 
Serious adverse event 

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SAP 
Statistical Analysis Plan 
SNRI 
Serotonin-norepinephrine reuptake inhibitor 
SOC 
System organ class 
SSRI 
Selective serotonin reuptake inhibitor 
SST 
Stop Signal Task 
TEAE 
Treatment-emergent adverse event 
tmax 
Time to maximum observed concentration 
TSD 
Trichotillomania Symptom Diary 
TTM 
Trichotillomania 
g 
Microgram 
M 
Micromolar 
US 
United States 
WHODD 
World Health Organization Drug Dictionary 

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3 BACKGROUND AND RATIONALE 
3.1 
Background 
 
Trichotillomania (TTM) is a chronic psychiatric illness characterized by the recurrent pulling 
out of one’s hair as well as the associated distress or functional impairment caused by this 
condition. It was not until the late 1980s that TTM was included in the Diagnostic and 
Statistical Manual of Mental Disorders (DSM) as an impulse control disorder. Recent studies 
have linked perturbations in glutamatergic neurotransmission and/or heightened levels of 
oxidative stress to the underlying pathophysiology of TTM. Imaging studies conducted in TTM 
patients identified alterations in areas of the brain, particularly those implicated in the 
regulation of urge control, rewarding behaviors, motor habits, mood, and executive function 
(Chamberlain et al., 2008; Chamberlain et al., 2010; Grant and Chamberlain, 2016; Roos et al., 
2015), as key contributors to the pathophysiology of TTM and related impulse control 
disorders (e.g., excoriation disorder). Additionally, functional deficits in glutamate signaling 
within the cortical-striatal pathway and mesolimbic system (i.e., nucleus accumbens) have 
been proposed to contribute to the underlying pathology and symptoms of TTM (Grant et al., 
2009). 
 
SXC-2023 is a novel small molecule and new chemical entity designed to activate System xc- 
(also known as the cysteine glutamate antiporter). By increasing cyst(e)ine levels, SXC-2023 
increases the activity of System xc- in the brain. System xc- is expressed on astrocytes and 
neurons within the central nervous system (CNS) and its primary function is to couple the 
uptake of one extracellular molecule of cystine to the release of one intracellular molecule of 
glutamate. As alterations in glutamate neurotransmission and/or oxidative imbalances are 
proposed to underlie the pathology of TTM, this mechanism of action is important because 
activation of System xc- is proposed to restore imbalances in oxidative stress and modulate 
glutamatergic neurotransmission in the brain. 
 
SXC-2023 is currently in clinical development (Investigational New Drug [IND] No. 133689) 
and proposed as a strategy to treat TTM in adults. 
 
Refer to the Investigator’s Brochure, Version 6.0 (SXC-2023, 2019) for detailed background 
information on SXC-2023. 
 
3.1.1 
Preclinical Trials 
 
3.1.1.1 
Pharmacology 
 
In preclinical rodent models, oral treatment with SXC-2023 was found to reduce anxiety 
behaviors as measured by an increase in the time spent in the open arm of the elevated plus 
maze (a symptom of many psychiatric disorders and a clear indication of CNS penetration) and 
ameliorate N methyl-D-aspartate receptor antagonist (MK-801)-induced deficits in pre- pulse 
inhibition, which tests sensory motor behaviors dependent on cortical glutamatergic 
transmission. Additionally, acute and chronic (7-day) administration of SXC-2023 
significantly lowered the number of lever presses to reinstatement cocaine-seeking behavior. 
These studies, coupled with a study using rats engineered to lack a functional cystine-glutamate 

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antiporter (specifically the xCT light chain protein), suggest that SXC-2023, through activation 
of System xc-, reverses deficits associated with glutamatergic dysfunction and heightened 
levels of oxidative stress implicated in the pathophysiology of impulse control disorders. 
 
3.1.1.2 
Pharmacokinetics 
 
Following oral administration of SXC-2023, the absolute bioavailability in dogs, the only 
species in which this has been studied, is 17.2%. 
 
SXC-2023 is rapidly absorbed in all species following oral administration, with peak plasma 
concentrations typically occurring within 2 hours post-dose. In whole blood, most of the SXC- 
2023 and N-acetylcysteine (NAC) (a metabolite of SXC-2023) are present in the plasma, with 
high protein binding (>96%) at a concentration of 10 µM (2.81 µg/mL). Compared to total 
plasma concentrations of drug, concentrations of SXC-2023 and NAC in red blood cells appear 
to be minimal when taking background levels into consideration. Metabolism of SXC-2023 
was evaluated using rat, monkey, dog, rabbit, and human hepatocytes. The primary metabolic 
pathway appears to include thioester cleavage, resulting in the formation of NAC and p-toluic 
acid. In rat, rabbit, monkey, and human hepatocytes, p-toluic acid undergoes subsequent 
glycine conjugation to form 4-methylhippuric acid. Another possible minor pathway of SXC- 
2023 metabolism includes deamidation followed by cysteine conjugation. 
 
The parent drug, NAC, and p-toluic acid have relatively short plasma half-lives (<6 hours). All 
the metabolites are polar; therefore, extensive renal clearance and urinary excretion are 
expected. 
 
Following in vitro studies to assess the potential of SXC-2023 to inhibit, induce, or be 
metabolized by cytochrome P450 enzymes, it is anticipated that the likelihood of drug-drug 
interactions with SXC-2023 is minimal, with a possible exception for inhibition of cytochrome 
P450 P2C8 (showing half-maximal inhibitory concentration of enzyme activity of 570 μM). In 
vitro data indicate that SXC-2023 may be a substrate of organic anion transporting polypeptide 
1B1 and 1B3, but not of P-glycoprotein or breast cancer resistance protein. 
 
3.1.1.3 
Toxicity 
 
The safety and toxicity associated with chronic SXC-2023 treatment was evaluated in 2 species 
(rats and dogs) following a 28- or 90-day dosing period. In the 90-day toxicity studies, the 
reversibility, persistence, or delayed occurrence of any SXC-2023-related effects was 
evaluated after a 28-day recovery phase. 
 
Once-daily oral administration of SXC-2023 for 28 days at 500, 1000, and 2000 mg/kg/day 
was generally well tolerated in both male and female rats (please see Investigator’s Brochure, 
Version 6.0 [SXC-2023, 2019] for detailed information and additional summary). The Study 
Director at the nonclinical contract research organization (CRO) considered the no observed 
adverse effect level (NOAEL) to be the highest dose tested (2000 mg/kg/day). However, given 
the increase in kidney weights and greater severity of findings in the kidney tubules at the 
highest dose in both sexes, Promentis conservatively considers the NOAEL to be 1000 
mg/kg/day. 

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A 90-day rat study was performed with SXC-2023 doses of 100, 300, and 1000 mg/kg/day. 
This study included a 28-day recovery arm to assess the reversibility, persistence, or delayed 
occurrence of any SXC-2023-related effects. Reversible, non-adverse clinical pathology 
findings included a higher incidence of ketones in the urine, mildly higher urine volume, and 
minimally to mildly lower urinary pH in males administered ≥300 mg/kg/day and females 
administered 1000 mg/kg/day. Mildly lower triiodothyronine and thyroxine serum levels 
occurred in males administered 1000 mg/kg/day and were not accompanied by any thyroid 
stimulating hormone changes or microscopic correlates. Microscopic findings at the terminal 
and recovery sacrifices were limited to minimal to moderate basophilic tubules and minimal 
to slight degeneration of tubules in animals administered 1000 mg/kg/day, which correlated 
with SXC-2023-related increased kidney weight parameters at the terminal sacrifice. Due to 
the mild severity of findings and the lack of impact on the health and well-being of animals 
administered SXC-2023, the NOAEL was 1000 mg/kg/day. 
 
In Beagle dogs, SXC-2023 was delivered once-daily for 28 days at 250, 500 and 1200 
mg/kg/day. Based on the results of these studies (please see Investigator’s Brochure, Version 
6.0 [SXC-2023, 2019] for detailed information and additional summary), the Study Director 
of the nonclinical CRO defined the NOAEL as 500 mg/kg/day; however, based on the similar 
exposure levels at 500 and 1200 mg/kg/day groups, Promentis conservatively defined the 
NOAEL to be 250 mg/kg/day. 
 
A 90-day dog study was performed with SXC-2023 doses of 30, 100, and 300 mg/kg/day, and 
included a 28-day recovery arm to assess the reversibility, persistence, or delayed occurrence 
of any SXC-2023-related effects. No SXC-2023-related findings or adverse microscopic or 
macroscopic findings were noted in this study. Similarly, no changes in measurements of 
hematology, immune system, ophthalmic or cardiovascular system were found in this 90-day 
dog toxicity study. Therefore, the NOAEL was determined to be 300 mg/kg/day. 
 
Good Laboratory Practice (GLP) development and reproductive toxicology studies have also 
been completed following chronic SXC-2023 treatment. Doses selected for these studieswere 
based on the results from previous non-GLP dose range finding studies in pregnant rats and 
rabbits. 
 
In a GLP study to test for effects resulting from SXC-2023 treatment to female Wistar 
Hannover rats on various fertility parameters, females were orally dosed with SXC-2023 at 
either 0, 100, 300 or 1000 mg/kg/day (n=22 female rats per dose group) once daily (QD) 
beginning 15 days before cohabitation, during cohabitation and continuing until Day 7 of 
gestation. All rats survived to scheduled euthanasia. There were no SXC-2023-relatedclinical 
observations or effects on body weight, body weight gain, food consumption, estrous cyclicity, 
mating and fertility, ovary weights, ovarian and uterine parameters or maternal gross necropsy 
findings at doses up to 1000 mg/kg/day. Therefore, the NOAEL of oral SXC-2023 in rats for 
both maternal toxicity and female fertility and early embryonic development was 1000 
mg/kg/day, the highest dose tested. 
 
In a study to detect adverse effects of SXC-2023 on pregnant Wistar Hannover rats and 
development of the embryo and fetus, female rats were orally dosed with SXC-2023 at either 
0, 100, 300 or 1000 mg/kg/day (n=20 rats per group) QD on Days 7 through 17 of gestation 

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(DGs 7 through 17). All rats survived to scheduled euthanasia on DG 21. There were no SXC- 
2023-related changes in mean maternal body weights, body weight gains or food consumption 
up to 1000 mg/kg/day, the highest dose tested. There were no SXC-2023-related changes in 
ovarian, uterine, or litter parameters, including embryo-fetal survival and mean fetal body 
weights. Lastly, there were no SXC-2023-related fetal external, visceral, or skeletal 
malformations or variations observed up to 1000 mg/kg/day, the highest dose tested. 
 
In a GLP study to assess possible adverse effects of SXC-2023 on pregnant New Zealand White 
rabbits and development of the embryo and fetus following daily oral exposure from 
implantation to closure of the hard palate (gestation day 7 to 19 [DG 7 to 19]), pregnant rabbits 
were orally dosed with SXC-2023 at either 0, 30, 100 and 300 mg/kg/day (n=20/dose group) 
QD on DG 7 to 19. One rabbit in the control group and one rabbit in the 300 mg/kg/day group 
aborted on DG 25. Additionally, one rabbit in the 300 mg/kg/day group was euthanized due to 
severe body weight loss and reduced food consumption on DG 24. Mean maternal body weight 
gain was lower than controls by 23% from DG 10 to 13, and by 35% from DG 16 to 20 (65% 
of the control). There was a mean maternal body weight loss for the interval DG 14 to 15 of 
-9.07g. During the post dose period, mean body weight gains in this group were higher than the 
control (131% of the control from DG 20 to 29) such that overall mean body weights on DG 
29 were comparable across all groups (including control). 
 
There were no SXC-2023-related changes in ovarian, uterine, or litter parameters, including 
embryo-fetal survival and mean fetal body weights up to 300 mg/kg/day. Mean male, female, 
and combined fetal weights were lower in the 300 mg/kg/day dose group compared to the 
control values (95%, 93%, and 94% of the control, respectively). Although these values were 
within the Testing Facility Historical Control Data, they were lower than the concurrent 
control. There were no SXC-2023-related fetal external or visceral malformations or variations 
observed up to 300 mg/kg/day. Fetal ossification site averages per fetus were comparable 
across all groups (including control). Based on the lower maternal body weight gain and body 
weight loss, reduced food consumption, at 300 mg/kg/day, the NOAEL of SXC-2023 was 
determined to be 100 mg/kg/day in this study. 
 
Based on results from a pivotal Ames mutagenicity assay, a human peripheral blood 
lymphocyte chromosome aberration assay, and an in vivo micronucleus assay in Wistar rats, 
SXC-2023 is considered not genotoxic. 
 
Refer to the Investigator’s Brochure, Version 6.0 (SXC-2023, 2019) for detailed information 
on SXC-2023. 
 
3.1.2 
Effects of SXC-2023 in Humans 
 
As described below, SXC-2023 has been investigated in a randomized, double-blind, placebo- 
controlled, single ascending dose (SAD) and food effect (FE) study in healthy subjects (PRO- 
101) and a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) 
study in healthy subjects (PRO-104). In both studies, SXC-2023 was administered as enteric 
capsule(s) in 50-mg or 200-mg unit dose strengths as single doses (up to 1600 mg) or multiple 
doses (up to 800 mg QD). Additionally, an open label oral contraceptive/drug-drug interaction 
(OC/DDI) study (PRO-103) to evaluate the pharmacokinetic (PK) effects of a 

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single dose of SXC-2023 (800 mg) and oral contraceptives (norethindrone [NET]/ethinyl 
estradiol [EE2]) was completed. 
 
Safety and PK findings are briefly summarized herein. Refer to the Investigator’s Brochure, 
Version 6.0 (SXC-2023, 2019) for further information about the safety and PK data of SXC- 
2023. 
 
3.1.2.1 
Safety 
 
To date, 96 human subjects have been exposed to SXC-2023. Overall, SXC-2023 has been 
safe and well tolerated in doses ranging from 50 mg to 1600 mg in the SAD/FE study, at a dose 
of 800 mg in combination with oral contraceptives, and at doses ranging from 200 mg to 800 
mg for 14 days in the MAD study. The most common adverse events (AEs) in subjects 
randomized to SXC-2023 in all Phase 1 studies include headache (frontal, generalized, 
occipital, or temporal) in 11% of subjects, dizziness in 5%, and constipation, myalgia and 
somnolence in 3% each. 
 
In all studies, changes from baseline in vital sign measurements and electrocardiogram (ECG) 
findings were also assessed. Vital signs were normal and no evidence of ECG abnormalities 
such as corrected QT (QTc) prolongation, was seen. In addition, no abnormal laboratory 
findings reported were considered clinically significant by the Investigator. 
 
In the PRO-103 and PRO-104 studies, safety laboratory results indicated that several subjects 
exhibited notable shifts in urinalysis measures of occult blood or red blood cells postdose. 
These were most likely due to several subjects with menses during the studies. 
 
PRO-101: SAD/FE Study 
 
The SAD/FE study examined the safety, tolerability and PK of single oral doses of SXC-2023 
ranging from 50 mg to 1600 mg. A total of 48 healthy, adult male and female subjects were 
enrolled in 6 cohorts of 8 subjects each (6 active and 2 placebo). 
 
SXC-2023 was safe and well tolerated. A total of 36 subjects were dosed with SXC-2023 on 
Study PRO-101 in six cohorts (50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1600 mg). 
Overall, AEs across body systems were mild or moderate. In subjects who received SXC-2023, 
the most common AEs were headache (in 5 subjects), followed by constipation, nausea, 
vomiting, and presyncope (in 2 subjects each). 
 
Safety was also assessed by the incidence of changes from baseline in clinical laboratory, vital 
sign measures, and ECG findings. Safety laboratory results and vital signs were normal and no 
evidence of ECG abnormalities, such as QTc prolongation, was seen. There were no serious 
adverse events (SAEs), study discontinuations related to AEs or deaths in this study. 
 
PRO-103: OC/DDI Study 
 
This open label OC/DDI study evaluated the effect of a single dose of SXC-2023 800 mg on 
the PK of single doses of 1 mg NET/0.035 mg EE2 (Ortho-Novum 1/35), in 28 healthy oral 
contraceptive-naïve females. A total of 4 subjects (14%) had AEs deemed possibly related to 

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study drug when SXC-2023 was taken in combination with EE2/NET. Grades 1 and 2 AEs 
included dizziness, generalized headache, and nausea. There were no SAEs reported or subject 
discontinuations in this study. 
 
PRO-104: MAD Study 
 
The MAD study examined the safety and tolerability of multiple oral doses (14 days) of SXC- 
2023 in four cohorts (200 mg QD, 400 mg QD, 400 mg twice daily [BID] and 800 mg QD) of 
10 subjects each (8 active and 2 placebo). Overall, SXC-2023 was well tolerated across all doses 
without any SAEs. Additionally, there were no subject discontinuations due to AEs, or deaths 
reported in this study. Adverse events were reported by 45% (18/40) of subjects regardless of 
attribution. The most common AEs in subjects was headache, reported by 15% (6/40) of 
subjects. All AEs were mild (Grade 1) to moderate (Grade 2) in severity in all dose groups; of 
those considered possibly related to study treatment, the majority of Grade 2 events were 
reported in the placebo group. All AEs resolved by the end of study, with the exception of 
constipation in one subject, and there were no clinically important trends in AEs, physical 
examination or clinical laboratory assessments. However, two subjects treated with SXC-2023 
with treatment emergent adverse events (TEAEs) of urinary tract infection or asymptomatic 
bacteriuria recorded notable post-baseline laboratory results, including positive shifts in 
urinalysis measures of occult blood, leukocyte esterase, and red and white blood cells, as well 
as positive urine nitrites and urine culture growth. 
 
Additionally, in cognitive safety outcome measures including Paired Associates Learning 
(PAL) to test episodic memory and Reaction Time (RTI), there were no impairments in 
cognitive performance. Furthermore, there were no significant trends in impulsivity scores 
across individuals or means as related to treatment, as measured by the Barratt Impulsiveness 
scale (BIS)or suicidality via the Columbia-Suicide Severity Rating Scale (C-SSRS). 
 
3.1.2.2 
Pharmacokinetics and Product Metabolism 
 
PRO-101: SAD/FE Study 
 
The PK of SADs of SXC-2023 was evaluated in Study PRO-101. Six cohorts of subjects 
received SADs of SXC-2023 (50 mg, 100 mg, 200 mg, 400 mg, 800 mg fasted, 800 mg fed, 
and 1600 mg). SXC-2023 concentrations were measurable in all subjects; NAC and p-toluic 
acid were measurable in a few sporadic samples across the dose levels tested. Plasma SXC- 
2023 concentrations increased with increasing dose and were dose-proportional to 1600 mg. 
On average, maximum observed concentration (Cmax) ranged from 1,094 ng/mL for the 50 mg 
dose to 35,217 ng/mL for the 1600 mg dose. Time to reach maximum observed concentration 
(tmax) was consistent across doses and was approximately 3.0 to 3.5 hours. The elimination 
half-life for SXC-2023 was approximately 3 to 6 hours over the 50 to 1600 mg dose range 
tested. Co-administration of SXC-2023 800 mg with a high-fat meal resulted in lower Cmax and 
a delay in tmax. Exposure, as assessed by area under the concentration-time curve (AUC), was 
slightly increased following administration of SXC-2023 with a high-fat meal. 

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PRO-103: OC/DDI Study 
 
Concomitant SXC-2023 administration does not have an impact on the PK of NET or EE2. 
Changes in EE2 drug exposure were not seen with concomitant SXC-2023 and the 90% 
confidence intervals for EE2 were within the 80-125% confidence limits demonstrating 
bioequivalence. For NET, the confidence intervals suggest that NET levels are slightly higher 
with concomitant SXC-2023; the test/reference ratios were 116% for Cmax and approximately 
124% for the AUC parameters and the upper bounds for the confidence intervals were just 
outside the 125% upper range. These changes, however, were not considered clinically 
relevant. 
 
PRO-104: MAD Study 
The PK of MADs of SXC-2023 was evaluated in Study PRO-104. Four cohorts of subjects 
received MADs of SXC-2023 (200mg QD, 400mg QD, 800mg QD and 400mg BID). SXC- 
2023 concentrations were measurable in all subjects; NAC (measured as total NAC) and p- 
toluic acid were detected at low concentrations across the dose levels tested. Plasma SXC-2023 
concentrations increased with increasing dose and were dose-proportional to 800 mg. On 
average, maximum observed concentration (Cmax) following 14 days of treatment ranged 
from 7,633 ng/mL for the 200 mg dose to 30,350 ng/mL for the 800 mg dose. Median time to 
reach maximum observed concentration (tmax) was consistent across doses and dosing days 
and ranged from 2-6 hours. The elimination half-life for SXC-2023 on day 1 was 
approximately 3.4 to 5.2 hours over the 200 to 800 mg dose range tested, and approximately 
9.4 to 11.7 hours on day 14. 
 
The urinary excretion data demonstrated that very little of the administered dose of SXC-2023, 
<0.2%, was excreted in urine over the 200 mg to 800 mg dose range. 
 
3.2 
Rationale 
 
3.2.1 
Rationale for this Study and Study Design 
 
SXC-2023 is a novel small molecule and new chemical entity designed to activate System xc- 
(also known as the cysteine glutamate antiporter). By increasing cyst(e)ine levels, SXC-2023 
increases the activity of System xc- in the brain. System xc- is expressed on astrocytes and 
neurons within the CNS and its primary function is to couple the uptake of one extracellular 
molecule of cystine to the release of one intracellular molecule of glutamate. As alterations in 
glutamate neurotransmission and/or oxidative imbalances are proposed to underlie the 
pathology of TTM, this mechanism of action is important because activation of System xc- is 
proposed to restore imbalances in oxidative stress and modulate glutamatergic 
neurotransmission in the brain. 
 
This study is being performed to evaluate the safety, tolerability, and activity of SXC-2023 on 
TTM when dosed for a period of 6 weeks. A randomized, double blind, placebo-controlled 
design was chosen to reduce bias. Neurocognitive testing and TTM-specific assessments will 
be performed at baseline, Week 3, and Week 6 to assess the effect of SXC-2023 administration 
over the duration of the treatment period. 

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3.2.2 
Rationale for Dose Selection 
 
The proposed doses of SXC-2023 in this study are 50 mg, 200 mg, and 800 mg QD. These 
doses were selected based on nonclinical activity of SXC-2023 in various rat models showing 
behavioral activity at a dose range of 10 to 30 mg/kg, which, based on allometric scaling, is 
equivalent to approximately 100 to 300 mg in human equivalent dosing. Extrapolation to 
humans suggests a daily dose of 200 mg which is the mid-point dose of this study. The 
additional doses of 50 mg and 800 mg are included to fully explore the dose response of SXC- 
2023. 
 
The safety and tolerability profile in the SAD/FE study performed in healthy male and female 
volunteers, where subjects received single doses up to 1600 mg, support the higher dose of 800 
mg proposed in the current study. Additionally, support for these doses comes from recent 
safety and tolerability profiles captured in a MAD study performed in healthy volunteers, 
showing that 14-day oral administration of SXC-2023 at 200 to 800 mg/day QD and 400 
mg/day BID, is generally safe and well tolerated. 
 
3.3 
Risks and/or Benefits to Subjects 
 
As mentioned in Section 3.1.2.1, SXC-2023 was studied in a Phase 1, double-blind, placebo- 
controlled, SAD/FE study (Study PRO-101) in healthy volunteers. SXC-2023 was safe and 
well tolerated at doses of 50 mg to 1600 mg. The safety monitoring practices employed by this 
protocol (i.e., physical examination, vital signs, 12-lead ECG, clinical laboratory tests, and AE 
questioning) were adequate to protect the subjects’ safety and detected all expected TEAEs. 
 
In the MAD study, SXC-2023 was safe and well tolerated at doses of 200 mg to 800 mg QD 
and 400 mg BID. The safety monitoring practices employed by this protocol (i.e., physical 
examination, vital signs, 12-lead ECG, neurocognitive testing, clinical laboratory tests, and 
AEs) are adequate to protect the subjects’ safety and detected all expected TEAEs. 
Additionally, cognitive tests were included as part of a broader cognitive safety assessment 
along with the C-SSRS to ensure that there were no CNS side effects. 
 
In the current study, subjects will be monitored to detect AEs during the study and followed 
appropriately to ensure resolution of AEs. Further, clinical laboratory tests, physical 
examination, vital signs, ECGs, neurocognitive assessments, and the C-SSRS will be used to 
evaluate safety. 
 
The approximate volume of blood planned for collection from each subject over the course of 
the study presents no undue risk to the subjects. 
 
A potential health benefit for study participants who receive SXC-2023 as blinded study drug 
is improvement in TTM symptoms. An indirect health benefit to subjects enrolled in this 
study is the free medical tests received at screening and during the study. 

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4 STUDY OBJECTIVES 
4.1 
Primary Objective 
 
• To explore the safety and tolerability of SXC-2023 in adults with TTM when dosed for 
a period of 6 weeks. 
 
4.2 
Secondary Objectives 
 
• To explore the activity of SXC-2023 in subjects with moderate to severe TTM when 
dosed for a period of 6 weeks using assessments of TTM disease activity (e.g., 
Trichotillomania Symptom Diary [TSD], Massachusetts General Hospital Hairpulling 
Scale [MGH-HPS], Clinical Global Impression of Severity and Change [CGI-S/CGI- 
C], and Patient Global Impression of Status and Change[PGI-S/PGI-C]). 
 
• To provide preliminary psychometric evidence of the reliability, validity, and 
responsiveness of the newly developed TSD assessment. 
 
4.3 
Exploratory Objectives 
 
• To test the activity of SXC-2023 on neurocognitive assessments (e.g., Stop Signal Task 
[SST], Cambridge Gambling Task [CGT] and other behavioral measures including 
Reaction Time [RTI], Paired Associates Learning [PAL], and Milwaukee Inventoryof 
Subtypes of TTM - Adult Version [MIST-A]). 
 
• To test the effects of SXC-2023 on whole blood glutathione levels. 
5 INVESTIGATIONAL PLAN 
5.1 
Overall Study Design and Plan 
 
This study is a randomized, double blind, placebo-controlled, multicenter study to evaluate the 
safety, tolerability, and activity of SXC-2023 (50 mg, 200 mg, or 800 mg QD) when dosed for 
6 weeks compared to placebo in adult subjects diagnosed with moderate to severe TTM. 
Subjects will be screened and will perform required assessments for eligibility during a 40-day 
screening period. During the screening period, subjects will be trained on site on how to use 
an electronic Patient Report Outcome (ePRO) handheld device to complete the TSD. After all 
screening assessments are complete, the subjects will complete the TSD at home every evening 
for 7 consecutive days during the screening period. 
 
On Study Day 1, eligible subjects will complete protocol-specified assessments and study 
procedures, including neurocognitive and other assessments, and will be assigned to receive 
one of three doses of SXC-2023 or matching placebo. Subjects will be assigned to treatment 
groups using a randomization scheme including a stratification factor for whether subjects are 
currently taking concomitant selective serotonin re-uptake inhibitors (SSRIs)/serotonin- 
norepinephrine reuptake inhibitors (SNRIs). Subjects will be instructed to complete the TSD 
on their ePRO handheld device every 24 hours (just prior to bedtime) during the 6-week 

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treatment period. Subjects will be instructed to take their study medication at approximately 
the same time each day (preferably in the morning at least 1 hour prior to or 2 hours after a 
meal). Subjects will return to the site to complete assessments at Week 3 (±4 days) and Week 6 
(±4 days). Subjects will then return for follow-up at Week 8 (±4 days). 
 
Neurocognitive and other behavioral measurements (in addition to the daily TSD) will include 
the following: 
 
Screening (neurocognitive and other behavioral measurements must be performed at one visit): 
 
• Mini-International 
Neuropsychiatric 
Interview 
(MINI) 
version 
7.0.2 
with 
Trichotillomania and Body Dysmorphic Disorder modules (MINI-TTM) 
 
• Training on the Cambridge Neuropsychological Test Automated Battery (CANTAB) 
iPad device which will be used for the SST, CGT, RTI, and PAL 
 
• Training on the TSD on the ePRO handheld device. Once trained, subject to complete 
the TSD on their ePRO handheld device every 24 hours for 7 days at home. 
 
• Training on the PGI-S, PGI-C, CGI-S, and CGI-C software using the iPad device 
• Barratt Impulsiveness Scale (BIS) 
• MGH-HPS 
• C-SSRS 
Day 1 (Baseline): 
• SST, CGT, RTI, and PAL (completed using the CANTAB iPad device) 
• MGH-HPS 
• PGI-S (completed using the iPad device) 
• CGI-S (completed using the iPad device) 
• C-SSRS 
• MIST-A 
Week 3 (±4 days): 
• MGH-HPS 
• PGI-S and PGI-C (completed using the iPad device) 
• CGI-S and CGI-C (completed using the iPad device) 

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• MIST-A 
• C-SSRS 
Week 6 (±4 days): 
• SST, CGT, RTI, and PAL (completed using the CANTAB iPad device) 
• MGH-HPS 
• PGI-S and PGI-C (completed using the iPad device) 
• CGI-S and CGI-C (completed using the iPad device) 
• MIST-A 
• C-SSRS 
Follow up/ET, 
Week 8 (±4 days): 
 
• C-SSRS 
Safety will be evaluated via reports of AEs, clinical laboratory tests, physical examinations, 
vital signs, the C-SSRS, ECGs, and concomitant treatments. Evaluation of AEs will include 
assessment of changes in psychiatric symptoms, including changes in emotions, cognition, or 
behavior, to determine whether changes are clinically significant (e.g., onset or exacerbation 
of depressed mood) and possibly related to study drug. 
 
Whole blood samples for glutathione measurements will be taken at baseline (prior to dosing) 
and at Week 6 (±4 days). 
 
The study design in outlined in Figure 1. The Schedule of Events is provided in Appendix A, 
and a list and description of the assessments performed at each study visit are presented in 
Section 7. 

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Figure 1          Diagram of Study Design 
 
 
 
 
 
QD=once daily; TSD=Trichotillomania Symptom Diary 
*Randomization will be stratified by concomitant use of SSRIs/SNRIs and no concomitant use of SSRIs/SNRIs. 
Notes: The screening period may be extended on a case-by-case basis. The screening visit may be split into multiple visits; 
however, the screening neurocognitive and other behavioral assessments must be performed at the same visit. 
 
 
5.2 
Study Duration 
 
Subjects will be dosed for 38 to 46 consecutive days. The maximum anticipated subject 
participation will be approximately 100 days (40 days for the screening period, 6 weeks of 
treatment, and a follow-up visit on Day 60 at the latest). One 10-day extension of the screening 
period may be permitted on a case-by-case basis with medical monitor or designee approval 
(e.g., if needed for adequate drug washout or additional ePRO training). 
 
5.3 
Study Conduct 
 
Please see the Schedule of Events (Appendix A) for a summary of the study assessments and 
procedures. Please see Section 7 for a listing and description of study procedures per visit. 
 
6 STUDY POPULATION 
6.1 
Number of Subjects 
 
Approximately 120 subjects are planned to be enrolled so that 100 subjects complete the study. 
In the event that a subject leaves the study (e.g., voluntarily withdraws, discontinues due to an 
AE, is lost to follow-up) prior to completing study procedures and assessments at the Week 3 
visit, an additional subject may be randomized. Subjects who leave the study following Week 3 
visit will be considered as part of the final enrollment sample of 120 subjects. 
 
6.2 
Eligibility Criteria 
 
6.2.1 
Inclusion Criteria 

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Subjects eligible for the study must meet all of the following inclusion criteria: 
 
1. Adult, female or male, 18-45 years of age, inclusive at screening. 
 
2. Has provided signed written informed consent with willingness and ability to comply 
with all aspects of the protocol. 
 
3. Diagnosis of current TTM based on Diagnostic and Statistical Manual of Mental 
Disorders, fifth edition (DSM-5) criteria and confirmed using the clinician- 
administered MINI-TTM. In addition, subjects should: 
 
a. Have a history of TTM for at least one year 
 
b. Have a history of daily hair pulling for at least 6 months prior to the first dose 
 
4. Except for SSRIs or SNRIs, has not used any psychoactive medications including, but 
not limited to, other antidepressants, anxiolytics, mood stabilizers, anti-psychotics, 
benzodiazepines, stimulants, sulfasalazine, and St. John’s Wort 30 days prior to first 
dose. Subjects will be allowed to maintain background therapy with SSRIs or SNRIs if 
on stable regimen for a minimum of 90 days prior to first dose and there are no 
anticipated changes to the SSRI/SNRI during course of trial. Please refer to Section 
6.2.3.2. 
 
a. Certain over-the-counter/herbal psychoactive drugs may be allowable with 
medical monitor approval (e.g., melatonin). 
 
5. Has not used NAC for at least 90 days prior to the first dose. 
 
6. Has not used gemfibrozil or repaglinide for 1 week prior to the first screening visit. 
 
7. Medically healthy with no clinically significant findings in medical history, physical 
examination, laboratory profiles (including coagulation), vital signs, or ECGs, as 
deemed by the Principal Investigator (PI) or designee. 
 
8. For a female of childbearing potential: either be sexually inactive (abstinent as a life 
style) for 28 days prior to the first dosing and throughout the study or be using one of 
the following acceptable birth control methods: 
 
• Oral contraception for at least 3 months prior to the first dosing along with either a 
physical (e.g., condom, diaphragm) or a chemical (e.g., spermicide) barrier method 
from the time of screening and throughout the study 
• IUD (either hormone-releasing or non-hormone releasing) for at least minimum 
duration per current labeling along with either a physical (e.g., condom, diaphragm) 
or a chemical (e.g., spermicide) barrier method from the time of screening and 
throughout the study 
• Depo contraception for at least minimum duration per current labeling prior to the 
first dosing along with either a physical (e.g., condom, diaphragm) or a chemical (e.g., 

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spermicide) barrier method from the time of screening and throughout the study 
• Double physical barrier method (e.g., condom and diaphragm) from 14 days prior to 
the first dose and throughout the studyPhysical plus chemical barrier method (e.g., 
condom with spermicide) from 14 days prior to the first dose and throughout the study 
• In addition, female subjects of childbearing potential will be advised to remain 
sexually inactive or to keep the same birth control method for at least 30 days 
following the last dose. 
 
9. Female of non-childbearing potential: must have undergone one of the following 
sterilization procedures, at least 6 months prior to the first dose: 
 
• hysteroscopic sterilization; 
• bilateral tubal ligation or bilateral salpingectomy; 
• hysterectomy; 
• bilateral oophorectomy; 
Or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with 
serum follicle stimulating hormone levels consistent with postmenopausal status or 
have medically documented history of biological or congenital sterility. 
10. A non-vasectomized, male subject must agree to use a condom with spermicide or 
abstain from sexual intercourse during the study until 30 days beyond the last dose of 
study drug/placebo. (No restrictions are required for a vasectomized male provided his 
vasectomy has been performed 4 months or more prior to the first dose of study 
drug/placebo. No restrictions are required for males with a medically documented 
history of biological or congenital sterility. A male who has been vasectomized less 
than 4 months prior to the first dose of study drug must follow the same restrictions as 
a non-vasectomized male). 
 
11. If male, must agree not to donate sperm from the first dose until 30 days after the last 
dose administration. 
 
12. Must be able to fluently read and write in English. 
 
13. Understands the study procedures in the informed consent form (ICF) and is willing 
and able to comply with the protocol. 
 
6.2.2 
Exclusion Criteria 
 
Subjects meeting any of the following criteria must NOT be enrolled in the study: 
 
1. Females who are pregnant or breastfeeding or intend to become pregnant during the 
study period or within 30 days of the final dose of study drug. 
 
2. Subjects engaged in cognitive behavioral therapy (CBT) for TTM or other body- 
focused repetitive behavior or any obsessive-compulsive related or impulse control 
disorder any time within 60 days prior to first dose. For other psychotherapies, subject 

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must have been engaged in that psychotherapy for a minimum of 60 days at the time of 
first dose and must be willing to maintain the same frequency and type of therapy for 
the duration of the study period. 
3. Subjects who have initiated any other behavioral interventions (e.g., wearable devices, 
behavioral self-help strategies) within 60 days prior to first dose. 
 
4. Subject is mentally or legally incompetent. 
 
5. Subject suffered a concussion in the past 6 months prior to screening. Any history of 
traumatic brain injury with loss of consciousness in the year prior to the first screening 
visit. 
 
6. Any lifetime history of any psychotic disorder, including schizophrenia, or any bipolar 
or bipolar-related disorder as determined by clinical history or confirmed at screening 
with the MINI, version 7.0.2. 
 
7. Current major depressive episode confirmed at screening with the MINI, version 7.0.2. 
 
8. Per PI judgment, the presence of any emotional problems or psychiatric disorders that 
may obscure evaluation of TTM or pose a risk to subject  safety or stability during  
the study period. Other emotional problems or diagnoses may include, but are not 
limited to, other body-focused repetitive behaviors, post-traumatic stress disorder, 
obsessive-compulsive disorder, panic disorder, compulsive gambling, borderline 
personality disorder, or antisocial personality disorder. 
 
9. History of any injury, illness, or condition that, in the opinion of the PI or designee, 
might confound the results of the study or poses an additional risk to the subject by 
their participation in the study. 
 
10. Laboratory evidence of renal impairment (e.g., a calculated creatinine clearance of < 80) 
 
11. Presence of any substance use disorder or, in the opinion of the PI or designee, 
problematic substance use (excluding nicotine or caffeine) within the past 2 years prior 
to screening. 
 
12. History of seizure disorder with the exception of subjects who have been off anti- 
seizure medication and have not had a seizure in the past 5 years. 
 
13. Subjects with any of the following: 
 
a. Any psychiatric hospitalizations in the past year, 
 
b. Imminent risk of suicide based on PI’s or designee’s clinical judgment or 
psychiatric examination, 
 
c. Active suicidal ideation in the past 6 months as evidenced by positive endorsement 
to Item 4 or 5 on the C-SSRS, 
 
OR 

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d. Any history of suicidal behavior in the past year as evidenced by positive 
endorsement to any of the suicidal behavior items on the C-SSRS. 
 
14. Has previously participated in any Promentis Phase 1 study. 
 
15. Participation in another interventional clinical study (including CBT or other 
behavioral interventions) within 30 days prior to the first screening visit. The 30-day 
window will be derived from the date of the last blood collection or dosing, whichever 
is later, in the previous study to the date of initiation of screening in the current study. 
 
6.2.3 
Restrictions 
 
6.2.3.1 
Cognitive Behavioral Therapy or Other Behavioral Interventions 
 
Subjects engaged in CBT for TTM or other body-focused repetitive behavior or any obsessive- 
compulsive related or impulse control disorder any time within 60 days prior to first dose visit 
will not be included in the study. For other psychotherapies, subject must have been engaged 
in that psychotherapy for a minimum of 60 days at time of first dose and must be willing to 
maintain the same frequency and type of therapy for the duration of the study period. 
 
Subjects who have initiated any other behavioral interventions (e.g., wearable devices, 
behavioral self- help strategies) within 60 days prior to first dose will not be included in the 
study. 
 
6.2.3.2 
Prior/Concomitant Medications 
 
Except for SSRIs or SNRIs, the subject must not have used any psychoactive medications 
including, but not limited to, antidepressants, anxiolytics, mood stabilizers, anti-psychotics, 
benzodiazepines, stimulants, sulfasalazine, and St. John’s Wort 30 days prior to first dose. 
Subjects will be allowed to maintain background therapy with SSRIs or SNRIs if on stable 
regimen for a minimum of 90 days prior to first dose and there are no anticipated changes to 
SSRI/SNRI during course of trial. 
 
Examples include but are not limited to the following: 
 
• SSRIs: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, 
vilazodone, and vortioxetine 
 
• SNRIs: venlafaxine, desvenlafaxine, levomilnacipran, and duloxetine 
Subjects who have used NAC within 90 days prior to the first dose will NOT be permitted in 
the study. 
 
Certain over-the-counter/herbal psychoactive drugs may be allowable with medical monitor 
approval (e.g., melatonin). 
 
Subjects should not have used gemfibrozil and repaglinide for 1 week prior to the first 
screening visit and may not use either of these medications during the course of the study. 

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6.2.3.3 
Alcohol, Cannabinoids and Melatonin 
 
Alcohol, cannabinoids and melatonin should not be used within 24 hours prior to all visits. 
 
6.2.3.4 
Contraceptive Requirements 
 
Contraceptive requirements for male subjects are as follows: 
 
• 
A non-vasectomized, male subject must agree to use a condom with spermicide or 
abstain from sexual intercourse during the study until 30 days beyond the last dose of 
study drug/placebo. (No restrictions are required for a vasectomized male provided his 
vasectomy has been performed 4 months or more prior to the first dose of study 
drug/placebo. No restrictions are required for males with a medically documented 
history of biological or congenital sterility. A male who has been vasectomized less 
than 4 months prior to the first dose of study drug must follow the same restrictions as 
a non-vasectomized male).Males must also agree not to donate sperm from the first 
dose until 30 days after the last dose administration. 
 
Contraceptive requirements for female subjects are as follows: 
 
1. For a female of childbearing potential: either be sexually inactive (abstinent as a life 
style) for 28 days prior to the first dosing and throughout the study or be using one of 
the following acceptable birth control methods: 
 
• 
 Oral contraception for at least 3 months prior to the first dosing along with either a 
physical (e.g., condom, diaphragm) or a chemical (e.g., spermicide) barrier method 
from the time of screening and throughout the study 
• IUD (either hormone-releasing or non-hormone releasing) for at least minimum 
duration per current labeling along with either a physical (e.g., condom, diaphragm) 
or a chemical (e.g., spermicide) barrier method from the time of screening and 
throughout the study 
• Depo contraception for at least minimum duration per current labeling prior to the 
first dosing along with either a physical (e.g., condom, diaphragm) or a chemical (e.g., 
spermicide) barrier method from the time of screening and throughout the study 
• Double physical barrier method (e.g., condom and diaphragm) from 14 days prior to 
the first dose and throughout the study. 
• Physical plus chemical barrier method (e.g., condom with spermicide) from 14 days 
prior to the first dose and throughout the study 
In addition, female subjects of childbearing potential will be advised to remain sexually 
inactive or to keep the same birth control method for at least 30 days following the last 
dose. 
 
2. Female of non-childbearing potential: must have undergone one of the following 
sterilization procedures, at least 6 months prior to the first dose: 
 
• Hysteroscopic sterilization 
• Bilateral tubal ligation or bilateral salpingectomy 

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• Hysterectomy 
• Bilateral oophorectomy 
Or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with 
serum follicle stimulating hormone levels consistent with postmenopausal status or 
have medically documented history of biological or congenital sterility. 
 
7 STUDY PROCEDURES 
7.1 
Screening Visit (Day −40 to Day 0) 
 
A screening log documenting all assigned subject numbers must be maintained in real time in 
the electronic database and at the site. A copy will be filed in the Investigator Binder. 
 
The following assessments/procedures will be performed at the Screening Visit. The screening 
assessments may be performed over multiple visits; however, all neurocognitive and other 
behavioral measurements must be performed at the same visit. 
• Informed consent must be obtained before any other study assessments or procedures. 
• Assessment of inclusion/exclusion criteria. 
• Demographics and medical and psychiatric history will be recorded. 
• Prior/concomitant medications taken within 90 days of the first screening visit will be 
recorded. 
 
• A physical examination will be performed. 
• Blood pressure and heart rate will be recorded after the study subject has been resting 
supine for ≥5 minutes. Respiratory rate and temperature may be taken at the same time. 
• A 12-lead ECG will be completed after the study subject has been resting supine for 
≥5 minutes. 
 
• A urine sample will be collected for a urine drug screen. 
• Safety laboratory tests (hematology, chemistry, coagulation, urinalysis) will be 
performed. 
 
• Urine pregnancy tests will be performed in female subjects (females with confirmed 
sterility (e.g. oophorectomy) are excluded). 
 
• The C-SSRS Screening version, MINI-TTM, BIS, MGH-HPS and CANTAB (training) 
will be completed. 
 
• Subjects will be trained using the iPad device, which will be used for the PGI-S, PGI-C, 
CGI-S, and CGI-C assessments. 

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• Any AEs occurring after informed consent is obtained will be recorded. AEs occurring 
during screening and up to pre-dose Day 1 that are not procedure related will be 
captured and reported as medical history 
 
• Subjects will be provided with an ePRO handheld device and will receive training on 
how to record TSD assessments daily. Subjects will use the ePRO device daily 
(evening before bedtime) to complete the TSD for a 7-day trial prior to the Day 1 
Visit, and these assessments will serve as baseline assessments. 
 
Prior to the subject’s return to the site after the 7-day trial period, a review of the daily TSD 
assessments will be performed by site and study designee and, if not completed for all 7 days 
(or if not 100% compliant), site will review reasons for non-compliance to determine if further 
training and re-administration of the 7-day TSD assessment is needed. Medical monitor or 
designee approval is required if re-training and re-administration of the 7-day trial TSD period 
is needed. 
If repeating the 7-day trial period requires an extension of the 40-day screening window, the 
screening window may be extended one time for an additional 10 days if the Medical monitor 
or designee approves. 
 
If subjects have engaged in 5 or fewer days of hairpulling, they will not be included in the 
study. If the site believes that there were extenuating circumstances and the subject typically 
engages in daily hairpulling, a repeat of the 7-day run-in period may occur with medical 
monitor or designee approval. 
 
7.1.1 
Screen Failures 
 
Subjects who sign an Informed Consent Form but are not randomized to the study must have 
a reason recorded as to why they were not enrolled in the study. This information will be 
recorded in the screening log maintained in the Investigator Binder. 
 
7.1.2 
Extension to the Screening Window 
 
Subjects who are unable to complete required screening procedures during the 40-day 
screening window may be eligible for one 10-day extension of the screening period. Sites must 
receive approval from the medical monitor or designee for such an extension prior to the end 
of the initial screening period and no later than the Baseline/Day 1 visit. 
 
7.1.3 
Re-screening 
 
Subjects may be re-screened 1 time if there is a change in the subject’s medical or psychiatric 
status, a modification of study entry criteria, or other relevant change impacting eligibility 
(e.g., additional ePRO training requirement). Re-screening must be approved by the medical 
monitor or designee prior to the subject returning for re-entry screening visit. 
 
7.2 
Day 1 
 
Subjects will arrive at the site on Day 1 and the following assessments/procedures will be 
completed: 

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Pre-dose 
 
• The site will assess any changes in the subject’s medical and psychiatric status or 
concomitant medications to confirm eligibility, prior to randomization. 
 
• A urine sample will be collected for a urine drug screen. 
• Urine pregnancy tests will be performed for female subjects (females with confirmed 
sterility (e.g. oophorectomy) are excluded). 
 
• A blood sample will be collected for blood chemistry, coagulation, and hematology 
tests, and a urine sample will be collected for urinalysis. 
 
• A blood sample will be taken for glutathione assessment. 
• The following testing will be performed: PGI-S, CGI-S, MIST-A, and MGH-HPS. The 
PGI-S and CGI-S will be assessed on an iPad device at the site. In addition, the SST, 
CGT, RTI, and PAL will be completed on the Cambridge Neuropsychological Test 
Automated Battery (CANTAB) iPad device. 
• C-SSRS SLV version 
Treatment assignment and dosing 
 
• After the above assessments have been completed, subjects will be randomized to 
receive SXC-2023 50 mg, 200 mg, or 800 mg or placebo. 
 
• Wallet cards containing study drug (capsules) in blister packs will be distributed on site 
by qualified personnel to confirm dosing requirements and initial dose will be 
administered on site (see Section 9.2 for dosing procedures). Subjects will be provided 
with 3 weeks of capsules of blinded study treatment to maintain the daily dosage until 
the Week 3 visit, along with an extra wallet card containing one additional week of 
study drug to allow for the variance in the time windows throughout the remainder of 
the treatment period. Subjects will be instructed to bring all unused capsules when 
returning for the Week 3 visit for accountability. 
 
Post-dose 
 
• Subjects will be given instructions to continue to record the TSD assessments daily 
throughout the 6-week treatment period using the ePRO device. Subjects will record 
the first assessment in the evening of Day 1, regardless of what time of day the subject’s 
visit took place. The assessments should be completed at the same time each day, in 
the evening before bedtime. 
 
• Subjects will be instructed to take study drug daily, preferably in the morning. Subjects 
will also be instructed that each dose should be taken at least 1 hour prior to a meal or 
at least 2 hours after a meal. Subjects should take study drug with water; however, they 
may also take a bite of applesauce, gelatin dessert, yogurt, or other soft food to help 
swallow the capsules (see Section 9.2 for details). 

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• Any AEs will be recorded. Evaluation of AEs throughout the study should include 
assessment of changes in psychiatric symptoms, including changes in emotions, 
cognition, or behavior, to determine whether changes are clinically significant (e.g., 
onset or exacerbation of depressed mood) and possibly related to study drug. 
 
7.3 
Week 3 (Day 21 [±4 days]) 
 
Subjects will return to the site, and the following assessments and procedures will be done: 
 
• An accounting of study drug doses brought in by the subject will be performed. 
Subjects will be provided with an additional 3 weeks of capsules of blinded study drug. 
They may use the extra capsules provided at Day 1 if needed to allow for the 4-day 
variance for the Week 6 visit. Subjects will be instructed to return all unused capsules 
when returning for the Week 6 visit. Subjects who have missed more than 5 consecutive 
doses or a total of 6 or more days of study drug administration will be dropped from 
the Per Protocol (PP) Population analyses and replaced. Subjects withdrawn from PP 
Population analyses for non-compliance will be given the option of completing the 
study, including continuing on study drug and completing assessments. 
 
• If the subject used 4 or more days of medication from the additional wallet card given 
at Day 1, an additional wallet card will be provided to the subject. 
 
• The TSD ePRO assessments will be reviewed prior to the completion of any Week 3 
visit procedures. Five consecutive days or a total of 6 or more days of non-compliance 
with daily TSD completion will result in the subject being withdrawn from PP 
Population analyses and replaced. Subjects withdrawn from PP Population analyses for 
non-compliance will be given the option of completing the study, including continuing 
on study drug and completing assessments. 
 
• A blood sample will be collected for blood chemistry, coagulation, and hematology 
tests, and a urine sample will be collected for urinalysis. 
 
• The following scales also will be administered: C-SSRS SLV version, PGI-S/C (iPad 
device), CGI-S/C (iPad device), MGH-HPS, and MIST-A. 
 
• Subjects will be reminded to continue the TSD ePRO assessments daily at 
approximately the same time each day (in the evening) and will be instructed to bring 
the device with them to the next visit. 
 
• Any AEs and concomitant medications will be recorded. Evaluation of AEs should 
include assessment of changes in psychiatric symptoms, including changes in emotions, 
cognition, or behavior, to determine whether changes are clinically significant (e.g., 
onset or exacerbation of depressed mood) and possibly related to study drug. 
 
7.4 
Week 6 (Day 42 [±4 days])/Early Termination Visit 
 
Subjects will return to the site, and the following assessments and procedures will be done: 
 
• A blood sample will be taken for clinical laboratory tests (blood chemistry, coagulation, 

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and hematology), and a urine sample will be collected for urinalysis. 
 
• A blood sample will be taken for glutathione assessment. 
• A 12-lead ECG will be completed after the study subject has been resting supine for 
≥5 minutes. 
 
• The SST, CGT, RTI, and PAL will be completed on the CANTAB iPad device. 
• The following scales also will be administered: PGI-S/C, CGI-S/C, MGH-HPS MIST- 
A, and C-SSRS. Note the PGI-S/C and CGI-S/C will be completed using the iPad 
device. 
 
• The ePRO devices will be collected. Five consecutive days or a total of 6 or more days 
of non-compliance with daily TSD completion since Week 3 visit will result in the 
subject being withdrawn from PP Population analyses. 
 
• Any returned study drug capsules will be collected and counted. Subjects who have 
missed more than 5 consecutive doses or a total of 6 or more days of study drug 
administration will be dropped from the PP Population analyses. 
 
• Any AEs or concomitant medications will be recorded. Evaluation of AEs should 
include assessment of changes in psychiatric symptoms, including changes in emotions, 
cognition, or behavior, to determine whether changes are clinically significant (e.g., 
onset or exacerbation of depressed mood) and possibly related to study drug. 
 
Note: If the subject terminates early, all of the assessments described above will be performed, 
with the following additions: physical examination, vital signs assessment, and urine 
pregnancy test (female subjects, subjects with confirmed sterility (e.g. oophorectomy) are 
excluded). 
 
7.5 
Follow-up (Day 56 [±4 days]), Week 8 
 
Subjects will be asked to return to the site for a follow-up visit. The following assessments will 
be performed: 
 
• A physical examination will be performed. 
• Blood pressure and heart rate will be recorded after the study subject has been resting 
supine for ≥5 minutes. Respiratory rate and temperature may be taken at the same time. 
 
• A blood sample will be taken for clinical laboratory tests (blood chemistry, coagulation, 
and hematology) and a urine sample will be collected for urinalysis. 
 
• Urine pregnancy tests will be performed for female subjects (females with confirmed 
sterility (e.g. oophorectomy) are excluded). 
 
• C-SSRS SLV version will be performed. 

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• Any AEs or concomitant medications will be recorded. Evaluation of AEs should 
include assessment of changes in psychiatric symptoms, including changes in emotions, 
cognition, or behavior, to determine whether changes are clinically significant (e.g., 
onset or exacerbation of depressed mood) and possibly related to study drug. 
 
7.6 
Unscheduled Visit 
 
An unscheduled telephone contact may be performed at the discretion of the investigator at 
any time during the course of the trial. 
An in-clinic unscheduled visit may be performed if a subject reports experiencing an AE via 
telephone contact or if the investigator has concerns about the subject’s safety. An unscheduled 
visit may be performed at any time during the study at the discretion of the investigator. The 
assessments performed at unscheduled visits will be done at the investigator’s discretion and 
results must be recorded in the electronic case report form (eCRF). 
 
7.7 
Early Withdrawal 
 
While subjects are encouraged to complete the study, all subjects are free to withdraw from 
participating in this study at any time and for whatever reason, specified or unspecified, and 
without prejudice. If the subject withdraws, the reason will be carefully documented in specific 
language. 
 
Reasons for premature discontinuation from the study, which will be listed on the Subject 
Disposition case report form (CRF), are defined as follows: 
 
Table 1 
Reasons for Discontinuation 
 
Adverse Event 
Subject is withdrawn from the study due to an AE. 
Complete AE form and attempt to follow the event until it is 
resolved or deemed stable. Subjects withdrawn prior to the Week 3 
visit may be replaced. 
Subject Request 
Subject withdraws consent. If reason is provided, explain in 
comments on Subject Disposition CRF. 
Protocol Deviation 
Investigator wishes to terminate the subject from study treatment due 
to a protocol deviation. Site monitor or Sponsor should be contacted 
before making decision. Comments/rationale should be documented 
in source documents. Subjects withdrawn prior to the Week 3 visit 
may be replaced. 
Missed Doses 
Subjects who have missed more than 5 consecutive doses or a total 
of 6 or more days of study drug administration will be dropped from 
PP Population analyses (and replaced if observed at Week 3). 
However, the subject would have the option of completing the study. 
ePRO Non-compliance 
Five consecutive days or a total of 6 or more days of non-compliance 
with daily TSD completion will result in the subject being withdrawn 
from PP Population analyses (and replaced if observed at Week 3). 
However, the subject would have the option of completing the study. 

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Lost to Follow-Up 
Subject does not return for scheduled visits. The Investigator will 
make reasonable efforts to contact subject and determine reason for 
discontinuation (phone call and if not reached by phone then follow 
with a registered letter). The site should make at least 3 attempts to 
contact the subject. If not reached, the subject will be documented as 
“lost to follow-up.” Subjects lost to follow-up prior to the Week 3 
visit may be replaced. 
Other 
Any other reason for early subject withdrawal from study treatment 
or the study. Explain in comments. Subjects withdrawn from study 
prior to the Week 3 visit may be replaced. 
 
AE=adverse event; CRF=case report form; ePRO=electronic Patient Reported Outcome; TSD=Trichotillomania 
Symptom Diary 
 
Subjects withdrawing prematurely after taking study drug must undergo the assessments 
described in Section 7.4. All study data from withdrawals must be retained and forwarded to 
the Sponsor. When an SAE or possibly or probably treatment-related AE persists at the end of 
the study, the PI will ensure a follow-up of the subject until the PI and Sponsor agree the event 
is satisfactorily resolved or stabilized. 
 
7.8 
Discontinuation of the Study 
 
The study will be discontinued if the Sponsor judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and Good Clinical 
Practice (GCP). 
 
 
8 CRITERIA FOR EVALUATION 
8.1 
Safety Evaluation 
 
8.1.1 
Medical History, Demographic and Other Baseline Information 
 
Medical history: 
 
• General medical/psychiatric/surgical history 
• Information collected includes condition/procedure, year of onset, and year ended or 
condition continuing 
 
• For procedures and events such as accidents or fractures, year of occurrence should be 
entered for both year of onset and year ended. 
 
• AEs that occur between time of consent and dosing that are not procedure related will 
be captured as past medical history. 
Medication history: 
 
• Information on all medications (investigational products, prescription, over-the- 
counter [OTC], and herbal medications) taken within the 90 days prior to the first 

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screening visit. 
 
Demographics: 
 
• Age (based on date of birth and date of screening visit) 
• Ethnic origin (Hispanic/Latino or Not Hispanic/Latino) 
• Race (White, American Indian/Alaska Native, Asian, Native Hawaiian or Other Pacific 
Islander, Black/African American) 
 
• Height (cm), without shoes 
• Body weight (kg), without shoes 
• Body mass index (weight [kg] / height [m2]) 
8.1.2 
Physical Examination 
 
A full physical examination will be performed as per the Schedule of Events (Appendix A). 
Symptom-driven physical examinations may be performed at other times, if deemed necessary 
by the PI or designee. 
 
8.1.3 
Vital Signs 
 
The following vital signs will be measured during the study: 
 
• Blood pressure (systolic and diastolic [mmHg]) 
• Heart rate (beats per minute) 
• Respiratory rate (breaths for minute) 
• Temperature 
Single measurements of blood pressure, heart rate, respiratory rate, and temperature will be 
performed as outlined in the Schedule of Events (Appendix A). Blood pressure and heart rate 
measurements will be performed after the study subject has been resting supine for ≥5 minutes. 
Blood pressure measurements will be taken with the appropriate cuff size using automated 
equipment. The same arm will be used for all measurements. 
 
8.1.4 
12-Lead Electrocardiograms 
 
Standard safety 12-lead ECGs will be performed during the study as outlined in the Schedule 
of Events (Appendix A). The 12-lead ECGs will be taken after the subject has been resting 
supine for ≥5 minutes. The following ECG parameters will be collected: PR interval, QRS 
interval, RR interval, QT interval, and QT corrected by Fridericia’s formula (QTcF) interval. 
 
All ECGs must be interpreted by a qualified physician for the presence of abnormalities. Any 
clinically significant ECG abnormality will be recorded as an AE. A subject will be withdrawn 

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from the study by the PI or his/her designee if, in their medical judgment, ECG findings are 
present which make continued study participation not in the subject’s best interest. 
8.1.5 
Clinical Laboratory Tests 
 
Blood and urine samples will be collected for routine clinical laboratory testing (hematology, 
chemistry, coagulation, and urinalysis) and analysis as outlined in the Schedule of Events 
(Appendix A). Additional, unscheduled testing may be performed during the study if medically 
indicated. 
 
Any value outside the normal range will be flagged for the attention of the PI or designee at 
the site. The PI or designee will indicate whether or not the value is of clinical significance. 
 
• If the result of any test (or repeat test, if done) from the samples taken during screening 
is indicated as clinically significant, the study subject will NOT be allowed into the 
study. 
 
• If a clinically significant abnormality is found in the samples taken after treatment, it 
should be recorded as an AE and the study subject will be followed until the test(s) has 
(have) normalized or stabilized. 
 
• Subjects with evidence of renal impairment (e.g. cCrCl <80) will NOT be allowed into 
the study. 
 
Blood sampling, processing, and storage instructions will be provided in a laboratory manual. 
Hematology, chemistry, coagulation, urinalysis, and urine drug screens will be assessed by a 
central laboratory. A local laboratory will be used to assess pregnancy tests. 
 
The following laboratory parameters will be reported: 
 
• Hematology: hemoglobin, hematocrit, red blood cell count, white blood cell count, 
leukocyte count with differential, mean corpuscular volume, mean corpuscular 
hemoglobin, mean corpuscular hemoglobin concentration, and absolute platelet count 
 
• Chemistry: sodium, potassium, chloride, albumin, glucose, blood urea nitrogen, 
creatinine, bilirubin (total and direct), alkaline phosphatase, aspartate aminotransferase, 
alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, and creatine 
phosphokinase 
 
• Coagulation: international normalized ratio, prothrombin time, activated partial 
thromboplastin time 
 
• Urine Pregnancy Test (in female subjects): Females with confirmed sterility (e.g. 
oophorectomy) are excluded. 
 
• Urinalysis: pH, specific gravity, glucose, ketones, nitrite, protein, bilirubin, leukocyte 
esterase, and blood will be performed. If urinalysis is positive for blood, protein, nitrite, 
and/or leukocyte esterase, microscopic urinalysis will be performed 

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• Urine drug screen: This test will screen for the following: amphetamines, barbiturates, 
benzodiazepines, cocaine (metabolite), methadone screen, opiates, phencyclidine, and 
propoxyphene. 
 
An estimate of blood draw volumes over the course of the study is provided in Appendix C. 
 
8.1.6 
Adverse Events 
 
For detailed information on collection, definition, categorization, and reporting of AEs/SAEs 
during the study, refer to Section 10. 
 
AEs will be monitored, and the following information recorded: 
 
• Standard medical terminology 
• Whether the event was a TEAE 
• Whether event was an SAE 
• Date and time of onset 
• Severity of event 
• Relationship of event to study drug 
• Action taken regarding study drug due to the event 
• Clinical outcome of event (resolved or ongoing) 
• If resolved, provide date of resolution 
8.1.7 
Prior and Concomitant Medications 
 
Site personnel should document any medications (prescription and OTC, including herbal 
medications and vitamins) the subject received within 90 days prior to screening and 
throughout the study. Recorded details should include: medication name, start date and time, 
stop date and time, dose, route, frequency, and reason for use and/or discontinuation (if 
applicable). The concomitant medication names will be coded according to the World Health 
Organization Drug Dictionary (WHODD) and classified by anatomical therapeutic chemical 
categories. 
 
8.1.8 
Columbia-Suicide Severity Rating Scale 
 
The C-SSRS will be used to evaluate suicidal ideation/behavior at times indicated in 
Appendix A. 

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8.2 
Neurocognitive and Other Behavioral Measurements 
 
The following measures will be assessed during the study: 
 
8.2.1 
Mini-International Neuropsychiatric Interview, version 7.0.2 with 
Trichotillomania and Body Dysmorphic Disorder Modules 
 
The MINI-TTM will be used at screening. 
 
8.2.2 
Barratt Impulsiveness Scale 
 
The BIS will be employed to capture trait impulsivity at screening. The scale is presented in 
Appendix E. 
 
8.2.3 
Cambridge Neuropsychological Test Automated Battery 
 
Subjects will be trained on the CANTAB iPad device with SST, CGT, PAL, and RTI at 
screening and the tests will be repeated as indicated in Appendix A. The SST and CGT will be 
used to assess impulsivity and inhibitory control. The PAL and RTI will be used to assess 
visual memory and motor/mental response speed, respectively. These assessments are 
described in further detail in Appendix F. 
 
8.2.4 
Massachusetts General Hospital Hairpulling Scale 
 
The MGH-HPS will be performed to assess TTM symptoms at times indicated in Appendix 
A. The scale is presented in Appendix G. 
 
8.2.5 
Patient Global Impression of Status/Change 
 
Subjects will use the iPad device to complete the PGI-S and PGI-C at the times indicated in 
Appendix A. 
 
Two PGI-S items will assess TTM severity from the subject’s perspective. The PGI-S items 
employ 5-point graded response scales and are as follows: 
 
• How would you rate your trichotillomania symptoms now? 
0 = None, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe 
 
• How much control do you feel you have over your trichotillomania symptoms now? 0 
= Complete control, 1 = Quite a bit of control, 2 = A moderate amount of control, 3 = 
A little control, 4 = No control 
 
Two PGI-C items (Lydick and Yawn, 1998; Cappelleri et al., 2014) will assess change in TTM 
severity from the subject’s perspective and are as follows: 
 
• Compared to the start of this study, how would you rate your trichotillomania 
symptoms now? 

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0 = Much better, 1 = Moderately better, 2 = A little better, 3 = About the same, 
4 = A little worse, 5 = Moderately worse, 6 = Much worse 
 
• Compared to the start of this study, how would you rate the strength of your urges to 
pull hair now? 
0 = Much weaker, 1 = Moderately weaker, 2 = A little weaker, 3 = About the same, 
4 = A little stronger, 5 = Moderately stronger, 6 = Much stronger 
 
8.2.6 
Clinical Global Impression of Severity/Change 
 
The CGI-S and CGI-C will be completed by the clinician using the iPad device at times 
indicated in Appendix A. 
 
The CGI-S (Guy, 1976) is a single-item rating that asks the clinician to evaluate the severity 
of the subject’s illness on a 7-point ordinal scale: 
 
“Considering your total clinical experience with this particular population, how ill is the patient 
at this time? (1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 
= Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients).” 
 
The CGI-C (Guy, 1976; Spearing et al., 1997) is a single-item rating that asks the clinician to 
evaluate the extent to which the subject’s symptoms have changed since baseline on a 7-point 
ordinal scale: 
 
“Compared to his/her condition at the baseline/Day 1 visit, how much have the patient’s 
trichotillomania symptoms changed? (1 = Very much improved; 2 = Much improved; 3 
= Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much 
worse.” 
 
8.2.7 
Milwaukee Inventory of Subtypes of Trichotillomania – Adult Version 
 
The MIST-A (Flessner et al., 2008) will be used to assess automatic and focused pulling 
subtypes at the times indicated in Appendix A. The scale is presented in Appendix H. 
 
8.2.8 
Trichotillomania Symptom Diary 
 
The ePRO device will be used by subjects to complete the TSD at home, every 24 hours for 
the 7 days during the screening period (baseline) and every day during the treatment period. 
Subjects will be instructed to complete the TSD assessment in evening. At Week 3, 5 
consecutive days or a total of 6 or more days of non-compliance with TSD completion will 
result in the subject being withdrawn from the Per Protocol Population analyses and replaced. 
At Week 6, 5 consecutive days or a total of 6 or more days of non-compliance with TSD 
completion since the Week 3 visit will also result in the subject being withdrawn from Per 
Protocol Population analyses. 
 
The scale is presented in Appendix D. 

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8.3 
Glutathione Blood Collection 
 
Whole blood samples will be collected at the times indicated in the Schedule of Events 
(Appendix A). Instructions for the sampling, processing, and storage of laboratory samples 
will be provided in the laboratory manual. 
 
9 TEST ARTICLE AND ADMINISTRATION 
9.1 
Test Article Identification, Supply, Packaging, Labeling, and Storage 
 
SXC-2023 will be supplied as 50 mg and 200 mg capsules for use in this study. Placebo 
capsules will be matching SXC-2023 to maintain the blind. Subjects will take 4 capsules of 
blinded study drug daily. 
 
Capsules will be supplied in blister packs within a wallet card. SXC-2023 is stable at room 
temperature and requires no special protection or handling; special protection from light is not 
required. SXC-2023 should be stored at 20℃ to 25℃, with excursions allowed between 15℃ 
to 30℃. 
 
All supplies will be packaged and labeled according to applicable local and regulatory 
requirements. All supplies must be stored in a locked area, accessible to authorized persons 
only, until needed for dispensing/dosing. 
 
9.2 
Study Drug Administration 
 
Subjects will be administered study drug at the clinical site at the Day 1 visit. The SXC-2023 
or placebo dose will be administered with water. Qualified personnel will administer study 
drug. After dosing, unit personnel will perform a hand and mouth check to ensure the subjects 
have swallowed the dose administered. 
 
The remaining doses will be self-administered by the subject every day for approximately 6 
weeks outside the clinic. Subjects will be instructed to take the dose at approximately the same 
time each day, preferably in the morning. Subjects will be instructed that each dose should be 
taken at least 1 hour prior to a meal and at least 2 hours after a meal. Subjects will be instructed 
to take study drug with water. If needed, subjects may also take a bite of applesauce, gelatin 
dessert, yogurt, or other soft food to help with swallowing the capsules. However, they should 
not fill the stomach with soft foods, and the site should request that they try water first. 
 
9.3 
Study Drug Accountability and Destruction 
 
The Sponsor will supply sufficient quantities of blinded study drug to allow completion of this 
study. The lot numbers and expiration dates (where available) of the study drugs supplied will 
be recorded in the final report. 
 
Subjects will be supplied with an appropriate amount of study drug at the Day 1 and Week 3 
visits to complete the planned doses and allow for variances in the study schedule. At Day 1, 
subjects will receive 4 weeks of study drug doses and at Week 3, subjects will receive 3 weeks 

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of study drug doses. The extra week of study drug provided at Day 1 will be used if needed to 
allow for time variances in the visit schedule throughout the treatment period. Subjects 
returning at the Week 3 visit who have used 4 or more days of study drug from the additional 
wallet card given at the Day 1 visit will be administered an additional wallet card. Subjects 
will be asked to bring all unused capsules at Week 3 and Week 6. Study site staff will record 
the number of capsules dispensed and number returned at each applicable visit. 
 
Records will be made of the receipt and dispensing of the study drugs supplied. At the 
conclusion of the study, any unused study drugs will be returned to the Sponsor or designee, 
or destroyed, as per Sponsor instructions. If no supplies remain, this fact will be documented 
in the product accountability records. 
 
9.4 
Blinding 
 
Subjects will be randomized to treatment assignments. Treatments will be double-blinded to 
avoid bias by the subject, PI, and study site staff. If the PI deems it is necessary to break the 
blind in the interest of a subject’s safety, individual unblinding may occur. The PI must attempt 
to contact the medical monitor and must document the reason for breaking the blind. 
 
9.5 
Randomization 
 
Subjects will be randomized in a 1:1:1:1 ratio to SXC-2023 50 mg, 200 mg, or 800 mg or 
placebo QD for approximately 6 weeks. The randomization will be stratified by whether the 
subject is receiving SSRI/SNRIs as the time of randomization. This stratification is to ensure 
balance among the treatment groups with respect to the number (%) subjects receiving these 
medications. There is no minimum requirement for the number of subjects with (or without) 
SSRIs/SNRIs in this study. 
 
9.6 
Missed Doses 
 
Subjects who miss more than 5 consecutive doses or 6 or more total days of study drug prior 
to or as assessed at the Week 3 visit will be dropped from PP Population analyses and replaced 
after subject completes the Week 3 assessments. Subjects withdrawn from analyses for non- 
compliance will be given the option of completing the study, including continuing on study 
drug and completing assessments. Subjects who miss more than 5 consecutive doses or 6 or 
more total days of study drug prior to or as assessed at the Week 6 visit will be dropped from 
PP Population analyses but not replaced after completion of Week 6 assessments. 
 
9.7 
Dose Suspension 
 
The PI may decide to suspend study drug in the case of an AE or concerns about the subject’s 
safety. Dose suspensions initiated via a telephone contact should be followed by an in-clinic 
visit (either scheduled or unscheduled visit) as soon as possible. Subjects with dose suspensions 
of 5 or fewer consecutive days can resume study drug, per PI discretion; however, if more than 
1 dose suspension is required during the course of the trial, medical monitor approval is 
required prior to resuming study drug. Subjects who require a dose suspension of longer than 
5 days will also require medical monitor approval to resume study drug. 

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9.8 
Medication Errors 
 
Any study drug administration or usage that is not in accordance with study protocol should 
be reported as a protocol deviation and any comments/rationale should be documented in the 
subject’s source documents, regardless of whether an adverse event (AE) results. 
Unintentional medication errors should be evaluated to provide appropriate correction and 
retraining as needed. Intentional medication errors (e.g., intentional misuse or abuse) should 
be discussed with the medical monitor to determine if subject should be withdrawn from the 
study. 
 
9.9 
Treatment of Overdose 
 
Standard symptomatic support measures should be used in the case of excessive pharmacologic 
effects or overdose. No antidotes are available. In the instance that a subject consumes more 
IP than per protocol, the subject will be instructed to contact the site. Gastrointestinal reaction 
is anticipated, and the subject should be clinically followed for 48 hours. 
 
10 ADVERSE EVENTS 
Starting at the time of informed consent, subjects will be asked to spontaneously report all AEs 
that occur during the trial until discharge from the study. Additionally, subjects will be queried 
about AEs at each study visit. AE queries should be performed in a nonspecific manner such 
as “How have you felt since the last visit?”, “How do you feel?”, or “Are there any recent 
changes to your health?” 
 
AEs occurring during screening and pre-dose Day 1 that are not procedure related will be 
captured and reported as medical history. AEs occurring after first dose of study drug will be 
captured in the AE page of the CRF. Non-serious AEs will be collected through the Follow-up 
visit. SAEs will be collected through 30 days post last dose (as reported through subject- 
initiated contact following the Follow-up visit). 
 
Evaluation of AEs should include assessment of changes in psychiatric symptoms, including 
changes in emotions, cognition, or behavior, to determine whether changes are clinically 
significant (e.g., onset or exacerbation of depressed mood) and possibly related to study drug. 
 
Cases of pregnancy that occur during the study or up to 30 days following last dose of study 
drug should be reported. Data on fetal outcome and breast-feeding are collected for regulatory 
reporting and drug safety evaluation. 
 
Study site personnel will record the occurrence and nature of each subject’s pre-existing 
conditions, including clinically significant signs and symptoms of the disease under treatment 
in the study. Any clinically significant findings from ECGs, laboratory tests, vital sign 
measurements, etc. that result in a diagnosis should be reported to Promentis or its designee 
and included as part of the subject’s medical history. After first dose of study drug, site 
personnel will record any change in the condition(s) and the occurrence and nature of any AEs. 
All AEs related to protocol procedures are reported to Promentis or designee. The PI will be 

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instructed to report to Promentis or its designee their assessment of the potential relatedness of 
each AE to protocol procedure and/or study drug via CRF. 
10.1 
Definition 
 
An AE can be any unfavorable and unintended sign, including an abnormal laboratory finding, 
symptom or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the study drug. 
 
A TEAE is any AE that newly appeared, increased in frequency, or worsened in severity 
following initiation of study drug. 
 
When an SAE or possibly or probably treatment-related AE persists at the end of the study, 
the PI will ensure a follow-up of the subject until the PI and Sponsor agree the event is 
satisfactorily resolved or stabilized. 
10.2 
Severity Scale for Adverse Events 
 
The severity of an AE is to be scored according to the following scale: 
 
Mild: 
Awareness of sign or symptom, but easily tolerated 
Moderate: 
Discomfort enough to cause interference with usual activity 
Severe: 
Incapacitating with inability to work or perform usual activity 
 
10.3 
Relationship to Study Drug 
 
The relationship of an AE to study treatment is to be assessed according to the following 
definitions: 
 
Unrelated: Should be reserved for those events which occur prior to study treatment orfor 
those events which cannot be even remotely related to study participation (e.g., 
injuries sustained in an automobile accident). 
Possible: 
The suspected AE may or may not follow a reasonable temporal sequence from 
study treatment administration but seems to be the type of reaction that cannot 
be dismissed as unlikely. The event could have been produced or mimicked by 
the subject’s clinical state or by other modes of therapy concomitantly 
administered to the subject. 
Probable: 
The suspected AE follows a reasonable temporal sequence from study treatment 
administration, abates upon discontinuation of the treatment, and cannot be 
reasonably explained by the known characteristics of the subject’s clinical state. 

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10.4 
Reporting Adverse Events 
 
All clinical events, including either observed or volunteered problems, complaints or 
symptoms are to be recorded on the AE page(s) of the CRF. The need to capture this 
information is not dependent upon whether the clinical event is associated with study treatment. 
Adverse clinical events resulting from concurrent illnesses or reactions to concurrent 
medications are also to be recorded. In order to avoid vague, ambiguous, or colloquial 
expressions, the AE should be recorded in standard medical terminology rather than the 
subject’s own words. 
 
Each adverse clinical event is to be evaluated for duration, severity, and whether the event may 
be associated with the study drug or other causes. Start and stop dates, relationship to study 
drug, medical management, and alternative causality of event must be recorded in the AE 
section of the CRF. SAEs and AEs believed to be possibly or probably related to study drug 
must be followed until resolution or stabilization. 
10.5 
Serious Adverse Events 
10.5.1 Definition 
 
An SAE is any untoward medical occurrence that at any dose results in any of the following 
outcomes: 
 
• Death 
• Is life threatening (an event in which the subject is at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have caused death if it 
was more severe) 
 
• A persistent or significant disability/incapacity 
• Results in congenital anomaly, or birth defect 
• Requires inpatient hospitalization or leads to prolongation of hospitalization 
(hospitalization for treatment/observation/examination caused by AE is to be 
considered as serious) 
 
• Other medically important events 
• Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations, such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above. These events, including those that may result in disability, 
should also usually be considered serious. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood 
dyscrasias or convulsions that do not result in hospitalization; or development of drug 

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dependency or drug abuse. If a subject becomes pregnant during treatment, this should 
be reported as if it were a SAE. 
 
Refer to Section 10.6 in case of pregnancy. 
10.5.2 Initial Reporting 
 
Any SAE, occurring in a subject receiving treatment or if the PI becomes aware of any SAE 
post-treatment, must be reported by the PI to the medical monitor and to Syneos Health Safety 
within 24 hours even if the SAE does not appear to be drug-related. This should be done by 
telephone or by sending a faxed or email copy of the SAE form plus other related information. 
 
A Sponsor Designee will contact you with any follow-up questions related to the event. 
 
The Sponsor Designee must be notified immediately of all deaths. Deaths must be reported, 
regardless of cause, from the time of informed consent and up to 28 days after completion of 
study medication administration, irrespective of the PI’s opinion regarding drug relationship. 
Documentation of cause of death and copy of autopsy or hospital report must be provided. 
Medical Monitor 
Robert Leadbetter, MD 
Medical Director 
Syneos Health 
Telephone: +1-919-601-2502 
Email: robert.leadbetter@syneoshealth.com 
 
Syneos Health Safety 
Fax: +1-877-464-7787 
Email: safetyreporting@syneoshealth.com 
 
10.5.3 Follow-up 
 
All additional follow-up evaluations must be reported to the medical monitor and Syneos 
Health Safety. Such data should be sent to the Sponsor within 10 calendar days. All SAEs will 
be followed until the PI and Sponsor agree the event is satisfactorily resolved. The Sponsor 
will be responsible for completing the safety report and for notifying the relevant authorities 
of any SAE as outlined in the International Conference on Harmonisation (ICH) Guidelines. 
The PI will also ensure that the appropriate ethics committee is notified of the SAE. 
10.6 
Pregnancy 
 
If a pregnancy does occur, each pregnancy must be reported by the PI to the Sponsor Designee 
using the Pregnancy Report Form within 24 hours of becoming aware of the pregnancy. The 
PI must follow up and document the course and the outcome of all pregnancies even if the 
subject was withdrawn from the clinical study. 

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Pregnancy alone is not regarded as an AE unless there is a suspicion that the study drug may 
have interfered with the effectiveness of a contraceptive medication. Elective abortions without 
complications should not be regarded as AEs, unless they were therapeutic abortions (see 
below). Hospitalization for normal delivery of a healthy newborn should not be considered an 
SAE. 
 
All outcomes of pregnancy must be reported by the PI to the Sponsor on the pregnancy 
outcome report form within 30 days after he/she has gained knowledge of the normaldelivery 
or elective abortion. 
 
Any SAE that occurs during pregnancy must be recorded on the SAE report form (e.g., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth or neonatal death]) and reported within 24 hours in accordance with the 
procedure for reporting SAEs. 
 
For more information on pregnancy reporting, please refer to the Safety Monitoring Plan. 
 
11 STUDY ADMINISTRATION 
11.1 
Ethics 
 
11.1.1 
Institutional/Independent Review Board 
 
This protocol and all appropriate amendments will be reviewed by an institutional/independent 
review board (IRB), and the study will not start until the IRB has approved the protocol or a 
modification thereof. The IRB is constituted and operates in accordance with the principles 
and requirements described in the United States (US) Code of Federal Regulations (CFR) (21 
CFR Part 56). 
 
11.1.2 
Ethical Conduct of the Study 
 
This study will be carried out in accordance with the protocol, US 21 CFR Parts 50, 56, and 
312, the ethical principles set forth in the Declaration of Helsinki, GCP, and the ICH 
harmonized tripartite guideline regarding GCP (E6 Consolidated Guidance, April 1996). 
 
11.1.3 
Subject Information and Consent 
 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and 
date an informed consent form summarizing the discussion prior to screening and will be 
assured that they may withdraw from the study at any time without jeopardizing their medical 
care. 
 
Subjects will be given a copy of their signed informed consent form. The requirements of 
informed consent are provided in Appendix B. 

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11.2 
Termination of the Study 
 
Promentis reserves the right to terminate the study in the interest of subject welfare. 
 
11.3 
Data Quality Assurance 
 
Designated personnel will be responsible for implementing and maintaining quality assurance 
(QA) and quality control systems to ensure that the study is conducted, and that data are 
generated, documented and reported in compliance with the study protocol, GCP and Good 
Laboratory Practice requirements as well as applicable regulatory requirements and local laws, 
rules and regulations relating to the conduct of the clinical study. 
 
All clinical data will undergo a 100% quality control check prior to clinical database lock. Edit 
checks are then performed for appropriate databases as a validation routine using SAS® or 
comparable statistical program to check for missing data, data inconsistencies, data ranges, etc. 
Corrections are made prior to database lock. 
11.4 
Direct Access to Source Data/Documents 
 
Site will ensure that the Sponsor, IRB and inspection by domestic and foreign regulatory 
authorities will have direct access to all study-related sites, source data/documents, and reports 
for the purpose of monitoring and auditing (ICH [E6] 5.1.2 & 6.10). In the event that other 
study-related monitoring should be done by other parties, they will be required to sign a 
confidentiality agreement prior to any monitoring and auditing. 
 
11.5 
Data Handling and Record Keeping 
 
Standard CRFs will be supplied. CRFs are printed off directly from the database. Each CRF 
is reviewed and signed by the PI. 
 
All raw data generated in connection with this study, together with the original copy of the 
final report, will be retained by Sponsor until at least 5 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 5 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period however if required by the applicable regulatory 
requirements or by an agreement with the Sponsor. It is the responsibility of the Sponsor to 
inform the PI/Institution as to when these documents no longer need to be retained. 
 
11.6 
Report Format 
 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common 
Technical Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH 
M2 Expert Working Group), the final report will be written according to the ICH E3 
Guideline (Structure and Content of Clinical Study Reports). 

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11.7 
Publication Policy 
 
All unpublished information given to site by the Sponsor shall not be published or disclosed to 
a third party without the prior written consent of the Sponsor. 
 
The data generated by this study are considered confidential information and the property of 
the Sponsor. This confidential information may be published only by the Sponsor or in 
collaboration with participating personnel from the Sponsor or upon Sponsor’s written consent 
to publish the article. 
 
12 STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a Statistical Analysis Plan (SAP). The SAP will be prepared bySyneos 
Health and agreed upon with the Sponsor. This document may modify the plans outlined in the 
protocol; however, any major modifications will be reflected in a protocol amendment. 
Additional statistical analyses other than those described in this section may be performed. 
These additions or changes to planned analyses will be documented in the SAP. 
 
Unless otherwise noted, continuous variables will be summarized using number of non- 
missing observations, mean, standard deviation, median, minimum, and maximum; categorical 
variables will be summarized using the frequency count and the percentage of subjects in each 
category. 
 
12.1 
Determination of Sample Size 
 
The primary objective of this study is to explore the safety and tolerability of SXC-2023 in 
adults with TTM when dosed for a period of 6 weeks. The sample size of this study (30 per 
group) was determined by reviewing other studies in this disease area and early stage of drug 
development (Chamberlain et al., 2018; Julious, 2010; Chow et al., 2008; Machin et al.,1997; 
Zar et al., 1984). The planned sample size of 30 per dose group is 80% powered to detect an 
effect size of 0.70 (Cohen’s d=0.70). This effect size for change in MGH-HPS total score 
corresponds to a change in the MGH-HPS of approximately 4 units (Grant et al., 2009). An 
effect size of 0.7 is in the range of 0.5 (medium) to 0.8 (large) effects. 
 
12.2 
Analysis Populations 
 
ITT Population (FAS): All subjects randomized to study drug will be included in the ITT 
population/full analysis set (FAS). 
 
Per Protocol (PP) Population: All subjects randomized to study drug and with no major 
protocol deviations will be included in the PP Population. The PP population will be used for 
the descriptive analyses of the neurocognitive and other behavioral tests. 
 
Safety Population: All subjects who receive a dose of the study drug will be included in the 
safety population. Safety summaries will use the safety population. 

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12.3 
Statistical Analysis 
 
12.3.1 
Subject Disposition 
 
The number of screen failures, subjects enrolled, completed, or discontinued from the study 
and the reason for study discontinuation will be tabulated by treatment group. The number of 
discontinued subjects will be broken down by treatment period of the study. Subject count by 
analysis population will be tabulated. Screen failures with reason for screen failure will be 
summarized. 
 
12.3.2 
Protocol Deviations 
 
Protocol deviations will be categorized as major or minor. Major deviations will be 
summarized by treatment group and type (reason) of deviation. Decisions regarding 
major/minor deviations will be determined by medical, data management and statistical review 
prior to database lock, as these deviations determine inclusion/exclusion in the PP population. 
 
Protocol deviations (both major and minor) will be included in the listings. 
 
12.3.3 
Demographics and Baseline Characteristics 
 
Demographics and baseline characteristics will be listed and summarized by treatment group 
and overall. 
 
12.3.4 
Safety Analysis 
 
All safety data will be listed with pertinent information, e.g., demographics, treatment group. 
Safety data will be summarized using descriptive statistics. Safety data will be listed and 
summarized in tabular and/or graphical form. No formal statistical testing will be performed 
on these safety data. Summaries will be provided by treatment group. Descriptive statistics will 
be calculated for quantitative safety data and frequency counts will be compiled for 
classification of qualitative safety data. 
 
12.3.4.1 
Adverse Events 
 
AEs will be collected after the first dose in the AE page of the CRF. AEs occurring during 
screening through pre-dose Day 1 that are not procedure related will be captured and reported 
as medical history. TEAEs will be defined as AEs with a start date after the first dose of the 
study drug. Non-serious AEs will be collected through the Follow-up visit. SAEs will be 
collected through 30 days post last dose (as reported through subject-initiated contact following 
the Follow-up visit). 
 
The number and percentage of subjects experiencing TEAEs, treatment-emergent SAEs, and 
TEAEs leading to study discontinuation will be summarized for treatment group/period by 
Medical Dictionary for Regulatory Activities® (MedDRA®) (most recent version) system 
organ class (SOC) and/or preferred term (PT). 
 
Summaries of TEAEs may include: 

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• by PT in descending order of frequency 
• by SOC and PT 
• by SOC, PT, and severity 
• by SOC, PT, and relationship to study drug (unrelated vs. related) 
AEs of possible or probable relationship to study drug will be combined for the “related” 
summaries. 
 
12.3.4.2 
Other Safety Assessments 
 
Summary statistics for vital signs, including blood pressure, heart rate, respiratory rate, and 
temperature, will be presented for each scheduled time point measured and for the change from 
baseline to each time point. 
 
Clinical laboratory data and change from baseline will be summarized by the scheduled time 
point. Subject incidences of change in classification with respect to the laboratory normal 
ranges will be summarized as shift tables. Baseline will be the last non-missing value obtained 
before randomization. Clinically significant clinical laboratory abnormalities will be reported 
and included in the AE tabulations. 
 
Clinically significant physical examination abnormalities will be reported and included in the 
AE tabulations. 
Screening and Week 6 ECGs will be summarized descriptively. 
The C-SSRS results will be summarized descriptively. 
12.3.4.3 
Concomitant Medications 
 
Concomitant medications will be coded using the most current WHODD and summarized by 
ATC code. All reported concomitant medications will be provided by randomized treatment 
group. 
 
12.3.5 
Analysis of Neurocognitive and Other Behavioral Measurements 
 
An efficacy outcome measure of focus is the MGH-HPS (Keuthen et al., 1995). The MGH- 
HPS is a 7-item self-report scale that rates urges to pull hair, actual amount of pulling, 
perceived control over the behavior, and distress associated with hair pulling in the past 7 days 
on severity scale from 0 to 4 for each item (total scores range from 0 to 28, with higher scores 
reflecting greater disease severity. Overall changes in the MGH-HPS and changes in MGH- 
HPS sub-factor 1 and sub-factor 2 scale scores will be analyzed. The percentage of subjects 
experiencing clinically significant change versus those not experiencing clinically significant 
changes based on CGI-S/CGI-C and the PGI-S/PGI-C will be compared using Fisher’s Exact 
Test. 

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Results of the BIS, SST, CGT, RTI, PAL, MGH-HPS, PGI-S/C, CGI-S/C, MIST-A, and TSD 
will be summarized descriptively by treatment. 
 
Change from baseline for MGH-HPS, PGI-S/C, CGI-S/C, MIST-A, and TSD will be analyzed 
using linear mixed models using treatment, SSRI/SNRI strata, visit, treatment by visit 
interaction as factors. Estimates of the treatment effect (least squares means with 95% 
confidence intervals) will be obtained from this model. Impact for potential covariates will be 
explored using this same model. Multiple imputation methods may be explored to determine 
the impact of missing responses. Supportive analysis of covariance models for the change from 
baseline at Week 3, Week 6, and the last available post-baseline value will be used. Estimates 
of treatment effect (least squares means with 95% confidence intervals) will be obtained. 
 
For SST, CGI, RTI, and PAL (collected only at Baseline and Week 6), analysis of covariance 
models for the change from baseline at Week 6 will be used. Estimates of treatment effect 
(least squares means with 95% confidence intervals) will be obtained. 
 
For the neurocognitive and other behavioral measurements, the primary analyses will use the 
PP Population. Subjects who miss more than 5 consecutive doses or a total of 6 or more days 
of study drug prior to or as assessed at the Week 3 visit will be dropped from PP Population 
analyses and replaced. Subjects withdrawn from analyses for non-compliance will be given the 
option of completing the study, including continuing on study drug and completing 
assessments. Subjects who miss more than 5 consecutive doses or 6 or more total days of study 
drug prior to or as assessed at the Week 6 visit will be dropped from PP Population analyses 
but not replaced. 
 
Five consecutive days or a total of 6 or more days of non-compliance with daily TSD 
completion at either the Week 3 or between the Week 3 and Week 6 visits will result in the 
subject being withdrawn from PP Population analyses (and replaced if observed at Week 3). 
 
Analyses may be repeated using the FAS. 
 
Planned analyses will follow standardized instruction manuals for neurocognitive assessments, 
where such manuals exist. 
 
Results will be presented with no adjustment for multiplicity. 
 
12.3.6 
Analysis of Glutathione Concentrations 
 
Glutathione levels will be summarized descriptively. 

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13 REFERENCES 
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 
Fifth Edition. 5th ed. Washington, DC: American Psychiatric Association; 2013. 251-254. 
Cappelleri JC, Zou KH, Bushmakin AG, Alvir JMJ, Alemayehu D, Symonds T. Patient- 
reported outcomes — measurement, implementation, and interpretation. London: Chapman& 
Hall/CRC; 2014. 
Chamberlain SR, Menzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K et al. Grey 
matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. Br 
J Psychiatry. 2008;193(3):216-21. 
 
Chamberlain SR, Hampshire A, Menzies LA, Garyfallidis E, Grant JE, Odlaug BL et al. 
Reduced brain white matter integrity in trichotillomania: a diffusion tensor imaging study. 
Arch Gen Psychiatry. 2010;67: 965–971. 
 
Chamberlain SR, Odlaug BL, Boulougouris V, Fineberg N, Grant JE. Trichotillomania: 
advances in neurobiology and treatment. Neurosci Biobehav Rev. 2018. In press. 
 
Chow SC, Shao J, Wang H. Sample Size Calculations in Clinical Research (Second Edition). 
Chapman & Hall/CRC. Boca Raton, FL: 2008. 
 
Flessner CA, Woods DW, Franklin ME, Cashin SE, Keuthen NJ. The Milwaukee Inventory 
for Subtypes of Trichotillomania-Adult Version (MIST-A): development of an instrument for 
the assessment of “focused’ and “automatic” hair pulling. J Psychopathol Behav Assess. 2008; 
30:20-30. 
 
Grant JE and Chamberlain SR. Trichotillomania. Am J Psychiatry. 2016;173 (9), 868-874. 
 
Grant JE, Odlaug BL, and Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment 
of trichotillomania. Arch Gen Psychiatry. 2009;66(7):756-763. 
 
Guy W. ECDEU assessment manual for psychopharmacology (United States Department of 
Health, Education, and Welfare Publication No. 76-338). Rockville MD: National Institute of 
Mental Health, 218-22; 1976. 
 
Julious SA. Sample Sizes for Clinical Trials. Chapman & Hall/CRC. Boca Raton, FL: 2010. 
 
Keuthen NJ, O’Sullivan RL, Ricciardi JN, Shera D, Savage CR, Borgmann AS, Jenike MA, 
Baer L. The Massachusetts General Hospital (MGH) Hair Pulling Scale, 1: development and 
factor analyses. Psychother Psychosom. 1995; 64(3-4):141-145. 
 
Lydick E, Yawn BP. Clinical interpretation of health-related quality of life data. In: Staquet 
MJ, Hays RD, Fayers PM, eds. Quality of life assessment in clinical trials — methods and 
practice. New York: Oxford University Press; 1998; 299-314. 
Machin D, Campbell M, Fayers P, Pinol A. Sample Size Tables for Clinical Studies, 2nd 
Edition. Blackwell Science. Malden, MA: 1997. 
 
Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin 

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Psychol. 1995; 5 (6):768-74. 
 
Roos A, Grant JE, Fouche JP, Stein DJ, and Lochner C. A comparison of brain volume and 
cortical thickness in excoriation (skin picking) disorder and trichotillomania (hair pulling 
disorder) in women. Behav Brain Res. 2015; 279: 255-258. 
Spearing MK, Post RM, Leverich GS, Brandt D, Nolen W. Modification of the Clinical Global 
Impressions (CGI) Scale for use in bipolar illness (BP): The CGI-BP. Psychiatry Res. 1997; 
73(3): 159-71. 
 
SXC-2023 Investigator’s Brochure, Version 6.0; 2019. 
 
Zar JH. Biostatistical Analysis (Second Edition). Prentice-Hall. Englewood Cliffs, New Jersey: 
1984. 

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APPENDIX A SCHEDULE OF EVENTS 
 
Procedures 
Screening 
Treatment 
Follow 
Up/ET 
Day -40 to 
Day 0 
Baseline 
Week 3 
Week 6 
Week 8 
Day 1 
Day 21 
±4 days 
Day 42 
±4 days 
±4 days 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Reconfirm eligibility2 
X (pre) 
Demographics 
X 
Medical and psychiatric history 
X 
X (pre) 
Physical exam 
X 
X 
Vital signs (BP, HR, RR, and 
temperature) 
X 
X 
Electrocardiogram 
X 
X 
Urine drug screen 
X 
X (pre) 
Safety labs (blood chemistry) 
X 
X (pre) 
X 
X 
X 
Safety labs (hematology) 
X 
X (pre) 
X 
X 
X 
Safety labs (coagulation) 
X 
X (pre) 
X 
X 
X 
Safety labs (urinalysis) 
X 
X (pre) 
X 
X 
X 
Urine pregnancy (females)4 
X 
X (pre) 
X 
MINI-TTM 
X 
Columbia-Suicide Severity 
Rating Scale 
X 
X 
X 
X 
X 
CANTAB (SST, CGT, RTI, 
PAL) 
X 
(training) 
X (pre) 
X 
Barratt Impulsiveness Scale 
X 
MGH-HPS 
X 
X (pre) 
X 
X 
PGI-S 
X (training) 
X (pre) 
X 
X 
PGI-C 
X 
X 
CGI-S 
X (pre) 
X 
X 
CGI-C 
X 
X 
MIST-A 
X (pre) 
X 
X 
Glutathione blood sample 
X (pre) 
X 
Study drug 
dispensing/accountability 
X 
X 
X 
TSD 
X3 
(Training and 
7 day run-in 
period) 
Every 24 hours 
Adverse events 
X 
X 
X 
X 
X 
Prior/concomitant medications 
X 
X 
X 
X 
X 
Abbreviations: BP=blood pressure; CANTAB= Cambridge Neuropsychological Test Automated Battery; CGI- 
S/C=Clinical Global Impression of Severity/Change; CGT=Cambridge Gambling Task; HR=heart rate; MGH- 
HPS=Massachusetts General Hospital Hairpulling Scale; MINI-TTM=Mini-International Neuropsychiatric Interview, 
version 7.0.2 with Trichotillomania and Body Dysmorphic Disorder modules; MIST-A=Milwaukee Inventory of 
Subtypes of TTM-Adult Version; PAL=Paired Associates Learning: PGI-S/C=Patient Global Impression of 
Status/Change; 
pre=pre-dose; 
RR=respiratory 
rate; 
RTI=Reaction 
Time; 
SST=Stop 
Signal 
Task; 
TSD=Trichotillomania Symptom Diary. 

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1 The screening period may be extended by 10 days on a case-by-case basis with medical monitor or designee 
approval. The screening assessments may be split across multiple visits; however, the screening neurocognitive 
and other behavioral assessments must be done at the same visit. 
2 On Day 1, the site will review any changes in medical/psychiatric history or concomitant medications to 
confirm eligibility in the study. 
3 ePRO: Training (Day 0) will be performed on site. After all of the screening assessments are complete, the 
subject will be instructed to complete the TSD at home every 24 hours (evening) for a 7-day run-in period 
within the screening window. 
4Subjects with confirmed sterility (e.g. oophorectomy) are excluded. 
 
Notes: 
Subjects who terminate early will be asked to return for the Week 6 assessments along with the following: 
physical examination, vital signs assessment, and urine pregnancy test (female subjects). 
Unscheduled visits may be performed at the Investigator’s discretion. Assessments performed at unscheduled 
visits will be done at the investigator’s discretion and results must be recorded in the electronic case report 
form. 

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APPENDIX B BASIC ELEMENTS OF INFORMED CONSENT 
a). Basic Elements of Informed Consent 
The following information must be provided to each subject in obtaining informed consent. The 
subject (or subject's legal representative) should be provided with a copy of the signed written 
informed consent. 
1. 
State that the study involves RESEARCH. 
a. Explain the PURPOSES of the research. 
b. State the expected DURATION of the subject'sparticipation. 
c. Describe the PROCEDURES to be followed. 
d. Identify any EXPERIMENTALprocedures. 
2. 
Describe any reasonably foreseeable RISKS OR DISCOMFORTS to the subject. 
3. 
Describe any BENEFITS to the subject or to others that may reasonably be expected from 
the research. 
4. 
Note appropriate ALTERNATIVE procedures or courses of treatment, if any, that might 
be advantageous to the subject. 
5. 
a. Describe the extent, if any, to which CONFIDENTIALITY of records identifying the 
subject will be maintained. 
b. Note that the Food and Drug Administration MAY INSPECT the records. 
6. 
For research involving more than minimal risk, explain if any COMPENSATION or 
medical treatments are available should injury occur. If so, explain (a) what they consist 
of, OR (b) where further information may beobtained. 
7. 
State whom to contact for ANSWERS to pertinent questions about (a) the research, and 
(b) research subject's rights, and (c) whom to contact in the event of a research-related 
injury to the subject. 
8. 
State that: 
a. 
participation is VOLUNTARY, 
b. 
refusal to participate will involve NO PENALTY or loss of benefits to which the 
subject is otherwise entitled, and 
c. 
the subject MAY DISCONTINUE participation at any time without penalty or loss of 
benefits to which the subject is otherwiseentitled. 

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b). Additional Elements of Informed Consent 
When appropriate, one or more of the following elements of information shall also be provided 
to each subject: 
1. 
A statement that the particular treatment or procedure may involve risks to the subject (or 
to the embryo or fetus, if the subject is or may become pregnant) which are currently 
unforeseeable. 
2. 
Anticipated circumstances under which the subject’s participation may be terminated by 
the Investigator without regard to the subject’s consent. 
3. 
Any additional costs to the subject that may result from participation in the research. 
4. 
The consequences of a subject's decision to withdraw from the research and procedures for 
orderly termination of participation by thesubject. 
5. 
A statement that significant new findings developed during the course of the research which 
may relate to the subject's willingness to continue participation will be provided to the 
subject. 
6. 
The approximate number of subjects involved in thestudy. 
 
c). The following statement shall be provided to each clinical trial subject in informed consent 
documents and processes. “A description of this clinical trial will be available on 
http://www.clinicaltrials.gov, as required by U.S. Law. This web site will not include information 
that can identify you. At most, the web site will include a summary of the results. You can search 
this web site at any time.” 
 
d). The informed consent requirements in these regulations are not intended to preempt any 
applicable federal, state, or local laws which require additional information to be disclosed for 
informed consent to be legallyeffective. 
 
e). Nothing in these regulations is intended to limit the authority of a physician to provide 
emergency medical care to the extent the physician is permitted to do so under applicable 
Federal, State, or Local law. 
 
 
REFERENCE: 21 CFR Part 50.25 -- PROTECTION OF HUMAN Subjects, Basic elements of 
informed consent. 

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APPENDIX C SUMMARY OF BLOOD DRAW VOLUMES 
 
 
 
 
 
 
 
 
 
 
Sample Type 
Number of 
Time 
Points 
Approximate 
Volume per Time 
Point (mL) 
Approximate Sample 
Volume Over Course 
of Study (mL) 
Laboratory safety tests (including 
hematology, coagulation, and chemistry) 
5 
7.2 
36 
Glutathione whole blood sample 
2 
6 
12 
Total Blood Volume (mL)→ 
48 

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APPENDIX D TRICHOTILLOMANIA SYMPTOM DIARY 
 
 
 
 
 
 
 
 
ePRO: Trichotillomania Symptom Diary 
CONFIDENTIAL 
 
 
 
 
1. In the past 24 hours, approximately how much time (total) did you spend 
pulling hair from your body? 
 
 Did not pull hair at all (in the last 24 hours) [Skip to Question 3] 
 Spent less than 1 minute pulling hair 
 Spent at least 1 minute but less than 1 hour pulling hair 
 
o 
Please enter total amount of time:  
minute(s) 
 
 Spent at least 1 hour pulling hair 
 
o 
Please enter total amount of time:  
hour(s) and   
 
minute(s) 
 
2. In the past 24 hours, approximately how many episodes of hair pulling 
did you have? Please count only different periods of time you spent 
pulling hair (rather than counting individual hairs you pulled). 
 
  
episodes 
 
3. In the past 24 hours, approximately how many times did you feel an 
urge to pull hair from your body? Please include every time you felt an 
urge to pull hair whether or not you actually pulled. 
 
  
times [If never, please enter 0 here and skip question 4.] 
 
4. In the past 24 hours, approximately how many times were you able to 
resist an urge to pull hair from your body? 
 
  
times [If none, please enter 0.] 
 
PROPRIETARY INFORMATION- DO NOT COPY 
The following questions listed in question #s 1-4, ask about hair pulling associated with 
trichotillomania. For each question, please provide a response that best describes your 
feelings and experiences in the PAST 24 HOURS to the best of your ability. 

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APPENDIX E BARRATT IMPULSIVENESS SCALE 
Note: this is a sample provided to indicate content only. 
DIRECTIONS: People differ in the ways they act and think in different situations. This is a 
test to measure some of the ways in which you act and think. Read each statement and put an
X on the appropriate circle on the right side of this page. Do not spend too much time on any 
statement. Answer quickly and honestly. 
Rarely/Never Occasionally Often Almost Always/Always 
1 I plan tasks carefully. 
2 I do things without thinking. 
3 I make-up my mind quickly. 
4 I am happy-go-lucky. 
5 I don’t “pay attention.” 
6 I have “racing” thoughts. 
7 I plan trips well ahead of time. 
8 I am self controlled. 
9 I concentrate easily. 
10 I save regularly. 
11 I “squirm” at plays or lectures. 
12 I am a careful thinker. 
13 I plan for job security. 
14 I say things without thinking. 
15 I like to think about complex problems. 
16 I change jobs. 
17 I act “on impulse.” 
18 I get easily bored when solving thought problems. 
19 I act on the spur of the moment. 
20 I am a steady thinker. 
21 I change residences. 
22 I buy things on impulse. 
23 I can only think about one thing at a time. 
24 I change hobbies. 
25 I spend or charge more than I earn. 
26 I often have extraneous thoughts when thinking. 
27 I am more interested in the present than the future. 
28 I am restless at the theater or lectures. 
29 I like puzzles. 
30 I am future oriented. 
 
Patton, Stanford, Barratt (1995). J Clin Psy, vol. 51, pp. 768-774 

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APPENDIX F CAMBRIDGE NEUROPSYCHOLOGICAL TEST 
AUTOMATED BATTERY 
 
 
Version 1.0 
20 July 2018 
 
Introduction 
 
The CANTAB Connect electronic data capture (EDC) system will be used to run cognitive 
tests, capture subject responses and record data for transfer to Cambridge Cognition Limited. 
 
The system offers a simple touch-screen interface to guide the test administrator through the 
process of entering required subject information e.g. subject number, any required 
demographic details and selecting the appropriate visit. The system then automatically 
administers the CANTAB tests for the subject and visit selected. 
 
The system informs the subject how to complete each CANTAB task and each task includes 
practice and assessed phases. The system automatically records all subject responses. 
CANTAB Connect automatically synchronizes with the server at the end of each session to 
transfer data to the secure server. 
 
The following CANTAB Connect tasks will be used in the clinical study. 
 
Reaction Time (RTI) 
 
In this reaction time task the participant must hold down a button at the bottom of the iPad 
screen, with the index finger of their dominant hand, until a yellow spot briefly appears in one 
of five circles at the top of the screen. Once the yellow spot has flashed in one of the circles 

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the subject must release the button and with the same finger touch inside the circle where the 
yellow spot appeared as quickly as they can. 
 
The voiceover introduces the RTI test to the participant explaining how the test should be 
completed. There is a short practice phase prior to the assessed phase. The participant will see 
five circles at the top of the screen and a button at the bottom of the screen. 
 
 
The voiceover prompts the participant to practice touching the button at the bottom of the 
screen and then informs the subject that they should hold this button down until a yellow spot 
flashes in one of the circles above. Once they see the yellow spot appear they should release 
their finger from the button as quickly as they can and using the same finger touch the circle 
where the yellow spot appeared. Once they have touched the circle they must return their finger 
to the button and hold the button until they see another yellow spot flash in one of the circles 
above and then once again touch the circle where the yellow spot appeared. 
 
 

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The RTI task includes a practice phase (10 trials) followed by the assessed phase. The 
voiceover reminds the subject that they should go as quickly as they can whilst trying to avoid 
making any mistakes. 30 assessed trials are then presented. 
 
The key outcome measures for this task are median reaction and movement time. 
 
Stop Signal Task (SST) 
 
The Stop Signal Task (SST) is a classic stop signal reaction time test that measures the 
participant’s ability to inhibit a response. The subject is shown two buttons on the screen, one 
on the right side of the screen and the other on the left hand side of the screen. Arrows appear 
in the middle of the screen and the participant learns to press the button corresponding to the 
direction in which the arrow points. 
 
The task starts with a practice phase where the subject simply responds by touching the button 
on the left side of the screen when the arrow points to the left and the button on the right hand 
side when the arrow points to the right. A stop signal (an auditory tone) is then introduced. If 
a stop signal is presented, the participant must inhibit their response i.e. try not to touch the on- 
screen button. A stop signal occurs on 25% of trials. 
 
 
 
 
 
The assessed phase with the stop signal (tone) is presented in 4 blocks. At the end of each 
assessed block, a graphic representing the participant’s performance is shown on screen. 
Depending on the participant’s performance on the previous block the participant is 
encouraged to either go faster or slower on the next block, whilst trying not to touch the button 
whenever they hear the tone. 

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The time between the arrow being shown on screen, and the delay interval between the 
participant hearing the tone (Stop Signal Delay (SSD)) is varied throughout the task. 
 
Paired Associates Learning (PAL) 
 
The Paired Associates Learning task consists of a number of stages, which the subject must 
complete in order. For each stage, boxes are displayed on the screen. These boxes are opened 
one at a time, in a randomised order. Two or more of the boxes will contain a pattern. The 
patterns shown in the boxes are then displayed in the middle of the screen, one at a time, and 
the subject must touch the box where the pattern was originally located. 
 
 

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When the participant successfully identifies the correct box for all of the patterns the test moves 
to the next level. The PAL test gradually becomes more difficult with the number of boxes that 
contain a pattern increasing from 2 trials with 2 boxes that contain a pattern, 1 trial with 4 
patterns, 1 trial with 6 patterns. Following successful completion of the trial with 6 boxes 
containing a pattern, 8 boxes are presented on the screen. 
 
If the participant is not successful, the boxes will reopen to remind the participant where the 
patterns were. The participant will have up to 4 chances to correctly identify the location of the 
patterns at each level. If the participant fails after 4 attempts at any level the test will end. If a 
participant is successful at the 8 box level the final level will show 12 boxes on screen with each 
box containing a pattern. 
 
 

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Cambridge Gambling Task (CGT) 
 
The participant is presented with a row of 10 color squares at the top of the screen. Some of 
the squares are blue in color others red. Beneath these colored squares are two buttons, one 
labelled red and the other blue. The participant is informed that a yellow token is hidden in one 
of the colored boxes. The participant should touch the red button at the bottom of the screen if 
they think it is more likely that the yellow token will be hidden in a red box or the blue button 
if they think it is likely to be hidden in a blue box. 
 
 
 
 
If the participant is correct they see the words You Win. If incorrect the participant will see 
You Lose. 
 
 

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In the assessed phase the participant is given 100 points and can bet on their decision. The 
proportion of the total score that the participant wants to bet is selected as the number on the 
screen counts up or down from 100% by tapping the Red or Blue box to place the desired bet 
amount. 
 
The participants total score increases or decreases incrementally dependent on successful or 
unsuccessful bet outcome. The total score is displayed at the top of the screen. 
 
 
 
 
The participant must try to amass as many points as possible. 

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APPENDIX G MASSACHUSETTS GENERAL HOSPITAL 
HAIRPULLING SCALE 
Note: this is a sample provided to indicate content only. 
 
Name:  
Date:  
 
 
Instructions: For each question, pick the one statement in that group which best describes your 
behaviors and/or feelings over the past week. If you have been having ups and downs, try to 
estimate an average for the past week. Be sure to read all the statements in each group before 
making your choice. 
 

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Scoring the Massachusetts General Hospital (MGH) Hairpulling Scale 
 
In scoring the MGH Hairpulling Scale, each item is scored on a 5-point scale from 0 = no 
symptoms to 4 = severe symptoms. The item scores are summed to produce a total score (range 
0 to 28). 
 
 
The Massachusetts General Hospital (MGH) Hairpulling Scale is copyrighted by © 1995 
Karger Publishers, Basel, Switzerland. Promentis has non-exclusive rights to reproduce and 
use for this study. For other uses of the scale, Karger Publishers should be contacted. 
 
 
Citation: Keuthen NJ, O’Sullivan RL, Ricciardi JN, Shera D, Savage CR, Borgmann AS, Jenike MA, Baaer L. 
The Massachusetts General Hospital (MGH) Hairpulling Scale: 1. Development and Factor Analyses. 
Psychotherapy and Psychosomatics 64:141-145, 1995. 

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APPENDIX H MILWAUKEE INVENTORY OF SUBTYPES OF 
TRICHOTILLOMANIA – ADULT VERSION 
Note: this is a sample provided to indicate content only. 
 

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The MIST-A is copyrighted by © 2008 Oxford University Press; Oxford United Kingdom 
has non-exclusive rights to reproduce and use for this study. For other uses of the scale, 
Oxford University Press should be contacted.