A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Food Effect of SXC-2023 When Administered Orally to Healthy Adult Subjects
Phase: PHASE1
Conditions: Healthy
Sponsor: Promentis Pharmaceuticals, Inc.

 
Page 1 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
 
 
 
 
 
 
Celerion Project No.:  CA22427 
 
Sponsor Project No.:  PRO-101 
 
US Pre-IND No.:  133689 
 
 
 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose 
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Food Effect of 
SXC-2023 when Administered Orally to Healthy Adult Subjects 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. and/or Celerion. Any viewing or disclosure of such information that is 
not authorized in writing by Promentis Pharmaceuticals, Inc. and/or Celerion is strictly 
prohibited. Such information may be used solely for the purpose of reviewing or performing 
this study. 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 2 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
1 
PROTOCOL REVISION HISTORY 
Date/Name 
Description 
17Jul2017  
by Ziv Machnes 
Final Protocol 
02Nov2017 
by Tricia Cotter 
Amendment 1 
• Red blood cell collection and analysis 
• Food effect dose selection requirement 
05Jan2018 
by Ziv Machnes 
Amendment 2 
• Addition of Cohort 6 (1600 mg SXC-2023) 
• Minor typographical and grammatical corrections 
 
 

05 Jan 2018

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 4 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
3 
ADDITIONAL KEY CONTACTS FOR THE STUDY 
Sponsor Contact for Serious Adverse 
Event Reporting 
Patricia P. Cotter 
Senior Director, Head of Clinical Operations 
Tel.:  +1 617 300-6172 
E-mail:  pcotter@promentispharma.com 
 
Protocol Author 
Ziv Machnes, PhD. 
Scientist II 
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.:  +1 514 744-8736 
Fax:  +1 514 744-8700 
E-mail:  ziv.machnes@celerion.com 
 
Certified Clinical Laboratory 
Celerion 
2420 West Baseline Road 
Tempe, Arizona 85283, USA 
Contact:  Ed Gritzfeld 
Tel.:  +1 602 437-0097 ext. 67172 
Fax:  +1 602 437-3386 
 
Bioanalytical Laboratory 
Covance BioAnalytic 
1121 East 3900 South, Building C 
Salt Lake City, Utah 84124, USA 
Contact:  Jeremy Thompson 
Tel:  +1 801 293-2306 
Fax:  +1 801 313-6495 
 
Pharmacokinetic and Statistical 
Analyses 
 
Celerion 
100 Alexis-Nihon Boulevard, Suite 360 
Montreal, Quebec H4M 2N8, Canada 
Tel.:  +1 514 744-9090 
Fax:  +1 514 744-8700 
 
and/or 
 
Celerion  
621 Rose Street 
Lincoln, Nebraska 68502, USA 
Tel.:  +1 402 476-2811 
Fax:  +1 402 939-0428 
 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 5 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
4 
TABLE OF CONTENTS 
1 PROTOCOL REVISION HISTORY ............................................................................. 2 
2 PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES ......................... 3 
3 ADDITIONAL KEY CONTACTS FOR THE STUDY ................................................ 4 
4 TABLE OF CONTENTS ................................................................................................. 5 
5 SYNOPSIS ......................................................................................................................... 8 
6 STUDY EVENTS FLOW CHART ............................................................................... 13 
7 ABBREVIATIONS ......................................................................................................... 15 
8 BACKGROUND AND RATIONALE .......................................................................... 18 
 
Background ............................................................................................................. 18 
8.1
 
Preclinical Trials ....................................................................................... 18 
8.1.1
 
Pharmacology ........................................................................... 18 
8.1.1.1
 
Pharmacokinetics ..................................................................... 19 
8.1.1.2
 
Toxicity .................................................................................... 19 
8.1.1.3
 
Rationale .................................................................................................................. 21 
8.2
 
Rationale for this Study and Study Design ............................................... 21 
8.2.1
 
Rationale for the Dose Selection............................................................... 21 
8.2.2
 
Risks and/or Benefits to Subjects ............................................................................ 22 
8.3
9 STUDY OBJECTIVES AND ENDPOINTS ................................................................. 23 
 
Study Objectives ..................................................................................................... 23 
9.1
 
Study Endpoints ...................................................................................................... 23 
9.2
10 INVESTIGATIONAL PLAN ........................................................................................ 24 
 Overall Study Design and Plan ............................................................................... 24 
10.1
 
Confinement, Return Visits, and Follow-Up ............................................ 24 
10.1.1
 
Study Duration .......................................................................................... 25 
10.1.2
 Study Conduct ......................................................................................................... 25 
10.2
 
Screening................................................................................................... 25 
10.2.1
 
Check-in Procedures (Day -1) .................................................................. 25 
10.2.2
 
Treatment Period (Day 1 to Day 4)........................................................... 26 
10.2.3
 Single-dose Administration ...................................................... 26 
10.2.3.1
10.2.3.1.1 Food Effect Group ........................................................... 26 
 Meal Schedule .......................................................................... 26 
10.2.3.2
 Activity ..................................................................................... 27 
10.2.3.3
 
End-of-Treatment ...................................................................................... 27 
10.2.4

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 6 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
Follow-up Visit / End-of-Study ................................................................ 27 
10.2.5
 
Scheduled End of Study ............................................................................ 28 
10.2.6
 Selection of Study Population ................................................................................. 28 
10.3
 
Number of Subjects................................................................................... 28 
10.3.1
 
Inclusion Criteria ...................................................................................... 28 
10.3.2
 
Exclusion Criteria ..................................................................................... 29 
10.3.3
 
Early Termination of Subjects from the Study ......................................... 30 
10.3.4
 
Prohibitions and Concomitant Medication ............................................... 31 
10.3.5
 Treatments ............................................................................................................... 32 
10.4
 
Treatments Administered .......................................................................... 32 
10.4.1
 
Repeat / Additional Dose Levels .............................................................. 33 
10.4.2
 
Dose Escalation and Stopping Rules ........................................................ 33 
10.4.3
 
Method of Assigning Subjects to Treatment Groups ................................ 33 
10.4.4
 
Blinding..................................................................................................... 34 
10.4.5
 Maintenance of Randomization ............................................... 34 
10.4.5.1
 Procedures for Breaking the Blind Prior to Study 
10.4.5.2
Completion ............................................................................... 34 
 Revealing of Randomization .................................................... 35 
10.4.5.3
 Interim Analysis ....................................................................... 35 
10.4.5.4
 
Treatment Compliance .............................................................................. 35 
10.4.6
11 STUDY PROCEDURES ................................................................................................ 36 
 Safety Assessments ................................................................................................. 36 
11.1
 
Body Height and Weight .......................................................................... 36 
11.1.1
 
Physical Examination................................................................................ 36 
11.1.2
 
Vital Signs ................................................................................................. 36 
11.1.3
 
12-Lead ECG Monitoring ......................................................................... 37 
11.1.4
 
Clinical Laboratory Tests .......................................................................... 38 
11.1.5
 
Adverse Events ......................................................................................... 39 
11.1.6
 Adverse Event Definition ......................................................... 39 
11.1.6.1
 Monitoring ............................................................................... 39 
11.1.6.2
 Reporting .................................................................................. 39 
11.1.6.3
 Serious Adverse Event ............................................................. 41 
11.1.6.4
 Pharmacokinetic Assessments ................................................................................. 42 
11.2
 
Blood Sampling and Processing ............................................................... 42 
11.2.1
 
Urine Sampling and Processing ................................................................ 42 
11.2.2
 
Analytical Method .................................................................................... 43 
11.2.3
 Blood Volume Drawn for Study Assessments ........................................................ 43 
11.3

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 7 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
12 DATA ANALYSIS .......................................................................................................... 44 
 Pharmacokinetic Parameters ................................................................................... 44 
12.1
 
For Plasma and Red Blood Cells .............................................................. 44 
12.1.1
 
For Urine ................................................................................................... 45 
12.1.2
 Statistical Methods .................................................................................................. 45 
12.2
 
Determination of Sample Size .................................................................. 45 
12.2.1
 
Subjects to Analyze................................................................................... 45 
12.2.2
 
Safety Evaluation ...................................................................................... 45 
12.2.3
 
Pharmacokinetic Analysis ......................................................................... 46 
12.2.4
 Descriptive statistics................................................................. 46 
12.2.4.1
 Food Effect Assessment ........................................................... 46 
12.2.4.2
 Dose Proportionality Analysis ................................................. 47 
12.2.4.3
13 STUDY ADMINISTRATION ....................................................................................... 48 
 Ethics ....................................................................................................................... 48 
13.1
 
Institutional Review Board ....................................................................... 48 
13.1.1
 
Ethical Conduct of the Study .................................................................... 48 
13.1.2
 
Subject Information and Consent.............................................................. 48 
13.1.3
 Termination of the Study ......................................................................................... 48 
13.2
 Data Quality Assurance ........................................................................................... 48 
13.3
 Direct Access to Source Data/Documents .............................................................. 49 
13.4
 Drug Supplies, Packaging and Labeling ................................................................. 49 
13.5
 Data Handling and Record Keeping ........................................................................ 49 
13.6
 Report Format ......................................................................................................... 49 
13.7
 Publication Policy ................................................................................................... 50 
13.8
14 REFERENCES ................................................................................................................ 51 
 
 
LIST OF TABLES 
Table 1: 
Blood Volume during the Study .................................................................... 43 
 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 8 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
5 
SYNOPSIS 
Compound: 
SXC-2023 
Clinical Indication: 
Treatment of trichotillomania (TTM) 
Study Phase and Type: 
Phase 1 – single ascending dose (SAD) and food effect (FE) 
first-in-human study. 
Study Objectives: 
Primary: 
To assess the safety and tolerability of SXC-2023 following 
administration of single ascending doses to healthy adult 
subjects. 
Secondary: 
Objective 1:  To assess the pharmacokinetics (PK) of SXC-2023 
in plasma, red blood cells (RBCs) (if applicable), and urine 
following administration of single ascending doses to healthy 
adult subjects. 
Objective 2:  To compare the single-dose PK of SXC-2023 in 
plasma, RBCs (if applicable), and urine following oral 
administration under fed and fasting conditions. 
Objective 3:  To assess the PK of SXC-2023 primary 
metabolites, N-acetylcysteine (NAC), and p-toluic acid, as 
available, in plasma, RBCs (if applicable) and urine, following 
administration of a single dose to healthy adult subjects. 
Summary of Study 
Design: 
This is a randomized, double-blind, placebo-controlled, SAD 
and FE study conducted at 1 study center in the United States 
(US). 
Subjects will participate in only one cohort. 
Up to 6 cohorts of 8 subjects each (6 active and 2 placebo) are 
planned for evaluation. 
Each cohort will include a sentinel group (1 active and 
1 placebo) who will be dosed at least 24 hours before the 
remaining 6 subjects (5 active and 1 placebo). Dosing of the 
remaining 6 subjects will be conducted following a safety 
evaluation of the sentinel group by the Principal Investigator 
(PI), Medical Monitor, and Sponsor. 
In each cohort, subjects will receive a single oral dose of 
SXC-2023 or placebo under fasting conditions, with one cohort 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 9 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
crossing over to receive the same dose of SXC-2023 or placebo 
for a second time under fed conditions. There will be a washout 
period of at least 7 days between dosing under fasting conditions 
and dosing under fed conditions (high-fat breakfast). 
Blood and urine samples will be collected predose through 
72 hours following SXC-2023 administration for the PK 
assessment of SXC-2023, NAC, and p-toluic acid, as 
appropriate. 
Dose escalation to the next dose level (i.e., next cohort) will not 
take place until a PI, Medical Monitor, and Sponsor 
representative have determined that adequate safety, tolerability, 
and PK plasma have been demonstrated regarding the previous 
cohort(s) to permit proceeding to the next cohort.  
The dose level (i.e., cohort) to be used for the assessment of a 
FE will be determined based on the safety, tolerability, and PK 
plasma evaluations of previous cohorts.  The safety and 
tolerability of the dose at least one dose level higher than the 
dose level selected for the FE cohort, may be evaluated. 
Safety (i.e., physical examinations, vital signs, 12-lead ECGs, 
clinical laboratory tests, and adverse events [AEs]) will be 
assessed throughout the study; serial blood samples and urine 
samples will be collected for these assessments. 
All subjects who received a dose of study drug/placebo 
(including subjects who terminate the study early) will return to 
the Clinical Research Unit (CRU) approximately 7 days after the 
last study drug/placebo administration for follow-up procedures, 
and to determine if any AEs have occurred since the last study 
visit. 
Study Population 
Subjects will be healthy male and female (women of 
non-childbearing potential [WONCBP]) subjects consisting of 
members of the community at large. 
Number of Subjects: 
This study is planned to enroll up to 48 subjects in 6 cohorts of 
8 subjects each (6 subjects to receive active drug and 2 subjects 
to receive placebo per the randomization). A sentinel group 
(1 active and 1 placebo) in each fasted cohort will consist of 
2 subjects who will be randomized to receive active drug or 
placebo. The remaining 6 subjects in the cohort will be 
randomized to receive active drug (n=5) or placebo (n=1). 
Attempts will be made to enroll 50% of each sex in each cohort. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 10 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Additional subjects may be enrolled if it is deemed appropriate 
by the PI, the Sponsor, and the Medical Monitor to repeat a dose 
level or to study an intermediate dose level (lower than those 
planned). 
Duration of 
Participation for 
Subjects 
The total planned duration of subject participation is 
approximately 35 days from screening to follow-up, with CRU 
confinement from check-in on Day -1 to Day 4 or approximately 
42 days for subjects enrolled to receive a second dose under fed 
conditions. 
Study Products 
SXC-2023 will be supplied as 50 mg and 200 mg capsules. 
Placebo will be provided as matching placebo capsules. 
An unblinded pharmacist will be responsible for providing 
SXC-2023 or placebo to the blinded study personnel for 
administration. 
Dosage, Dosage Form, 
Route, and Dose 
Regimen: 
Each cohort will start with a sentinel group of 2 subjects 
(1 active and 1 placebo) who will be dosed at least 24 hours 
before the remaining 6 (5 active and 1 placebo). 
Subjects in each cohort will receive a single oral dose of 
SXC-2023 or placebo on Day 1, under fasting conditions. 
Planned doses will be as follows: 
Cohort 1:  50 mg (1 x 50 mg capsule) SXC-2023 or matching 
 
placebo 
Cohort 2:  100 mg (2 x 50 mg capsules) SXC-2023 or 
 
matching placebo 
Cohort 3:  200 mg (1 x 200 mg capsule) SXC-2023 or 
 
matching placebo 
Cohort 4:  400 mg (2 x 200 mg capsules) SXC-2023 or 
 
matching placebo 
Cohort 5:  800 mg (4 x 200 mg capsules) SXC-2023 or 
 
matching placebo 
Cohort 6:  1600 mg (8 x 200 mg capsules) SXC-2023 or 
 
matching placebo 
One cohort will receive the same dose of SXC-2023 or placebo 
for a second time under fed conditions following a washout 
period of at least 7 days. The dose levels (i.e. cohort) to be used 
for the FE cohort will be determined based on the safety, 
tolerability, and PK plasma data from previous cohorts. The 
safety and tolerability of the dose at least one dose level higher 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 11 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
than the dose level selected for the FE cohort, may be evaluated. 
When administered under fed conditions, SXC-2023 will be 
administered orally following a high-fat breakfast. 
All doses of study drug/placebo will be administered with 
approximately 240 mL of water. In Cohort 6, if the study drugs 
cannot all be swallowed at the same time, the drug 
administration may be divided; however, dosing should be 
completed within 10 minutes. Additional water, up to a 
maximum of 50 mL may be administered as required by the 
subject. 
Safety Assessments 
Safety will be monitored through physical examinations, vital 
signs, 12-lead ECGs, clinical laboratory tests, and AEs. 
Safety Analysis 
The following analyses will be performed; however, no formal 
inferential statistics will be done on safety assessments. 
The placebo subjects from all cohorts will be pooled into a 
single placebo group for all summaries and presentations. 
Descriptive statistics will be calculated for quantitative safety 
data and frequency counts will be compiled for classification of 
qualitative safety data.   
Adverse Events: 
AEs will be coded using the most current version of MedDRA® 
available at Celerion.  
A by-subject treatment-emergent AEs (TEAEs) data listing, 
including verbatim term, preferred term, treatment, severity, and 
relationship to drug, will be provided. 
The number of subjects experiencing AEs and number of AEs 
will be summarized by cohort using frequency counts. 
Medical History and Physical Examination: 
Medical history will be listed by subject. 
Clinical Laboratory Results, Electrocardiograms, and Vital 
Signs Measurements: 
All clinical laboratory results, 12-lead ECGs, vital signs 
measurements, and their change from baseline, will be 
summarized by treatment and time point of collection. 
A shift table describing out-of-normal range shifts will be 
provided for clinical laboratory results. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 12 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Concomitant Medications: 
Concomitant medications will be coded using the most current 
World Health Organization (WHO) drug dictionary available at 
Celerion and listed by treatment. 
Pharmacokinetic Sample 
Collection 
Serial blood and urine samples will be collected prior to and 
through 72 hours postdose on Day 1 to determine the 
concentration of SXC-2023, NAC, and p-toluic acid in plasma 
and urine. For doses greater than or equal to (≥) 200 mg, RBCs 
will be collected to assess analytes, if applicable. 
The sampling schedule may be modified based on the results 
from previous cohorts. 
Pharmacokinetic 
Parameters and Analysis 
The following PK parameters will be calculated for SXC-2023, 
NAC, and p-toluic acid in plasma and RBCs, as appropriate, 
following SXC-2023 administration under fasted and fed 
conditions:   
AUC0-t, AUC0-inf, Cmax, Tmax, CL/F (parent only), Vz/F 
(parent only), Kel, and T½. 
The following PK parameters will be calculated for SXC-2023 
NAC, and p-toluic acid in urine, as appropriate, following 
SXC-2023 administration under fasted and fed conditions:  
Aet1-t2, Ae0-72, CLr, and %Fe (parent only). 
Additional PK parameters may be calculated, if deemed 
appropriate. 
The effect of food on a single oral dose of SXC-2023 will be 
assessed by comparing appropriate plasma and RBCs (if 
appropriate) PK parameters (i.e., AUC0-t, AUC0-inf, and Cmax) 
under fed versus fasting conditions using an analysis of variance 
(ANOVA) approach. 
Dose proportionality may be assessed using the power model 
approach, as appropriate. 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 13 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
6 
STUDY EVENTS FLOW CHART 
Study Procedures a 
S b 
Study Days in Each Cohort c 
FU d 
Days → 
-1 
1 
2 
3 
4 
Hours → 
C-I e 
0 
0.083 0.167 0.25 0.5 0.75 
1 1.5 2 
3 
4 
6 
8 
12 
16 f 
24 48 
72 
Administrative Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X g 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full Physical Examination h 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X i 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X j  
 
Vital Signs (HR and BP) 
X 
 
X i 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
X 
X 
X j 
X 
Vital Signs (RR and T) 
X 
 
X i 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
X 
X 
X j 
X 
Hem, Serum Chem k, and UA  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X j 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Preg Test (♀ only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X j 
 
Serum Total Testosterone, LH, and FSH l 
X m 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X j  
 
Urine cotinine Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Alcohol and Drug Screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/Hepatitis Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE Monitoring 
 
X 
X 
Concomitant Medication Monitoring 
X 
X 
 
Study Drug / Placebo Administration / PK 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SXC-2023 / Placebo Administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for SXC-2023, NAC, and p-toluic acid PK p 
 
 
X n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X j 
 
Urine for SXC-2023, NAC, and p-toluic acid PK 
 
 
X o 
 
Other Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confinement in the CRU 
 
X 
 
Visits 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 14 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
a: 
For details on Procedures, refer to Section 11. 
b: Within 28 days prior to first dose administration. 
c: 
For subjects in the FE cohort, there will be a washout period of at least 7 days between doses. 
d: All subjects who received a dose of study drug/placebo (including subjects who terminate the study early) will return to the CRU approximately 7 days after 
the last study drug/placebo administration for follow-up procedures, and to determine if any AE has occurred since the last study visit. 
e: 
Subjects will be admitted to the CRU on Day -1, at the time indicated by the CRU. 
f: 
The 16-hour time point following dosing on Day 1 will be either on Day 1 or Day 2, depending on the time of dosing on Day 1. 
g: For subjects in the FE cohort, to be performed in the fasted treatment only. 
h: Symptom-driven physical examination may be performed at other times, at the PI’s or designee discretion. 
i: 
To be performed within 24 hours prior to dosing on Day 1. 
j: 
To be performed at the end of treatment or prior to early termination from the study. For subjects in the FE cohort to be performed at the end of each 
treatment period or prior to early termination from the study 
k: Samples for serum chemistry will be obtained following a fast of at least 8 hours, however, in case of dropouts or rechecks, subjects may not have fasted for 
8 hours before the serum chemistry sample is taken. 
l: 
Samples for serum total testosterone, LH, and FSH will be collected at the same clock time (±1 hour) in the morning (before 10:00 AM) on each scheduled 
day, except for sample for FSH collected from postmenapausal women at screening. 
m: At screening, only samples for FSH from postmenopausal women will be collected. 
n: To be performed prior to dosing. 
o: Urine collection intervals are predose, and 0-1, 1-2, 2-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours postdose. 
p:    Includes red blood cell collection and analysis (if applicable) in doses ≥ 200 mg. 
 
Abbreviations:  ♀ = Females, ≥ = greater than or equal to, AE = Adverse events, BP = Blood pressure, C-I = Check-in, Chem = Chemistry, CRU = Clinical 
research unit, ECG = Electrocardiogram, EOT/ET = End-of-Treatment or early termination, FE = Food effect, FSH = Follicle-stimulating hormone, 
FU = Follow-up, Hem = Hematology, HIV = Human immunodeficiency virus, HR = Heart rate, LH = Luteinizing hormone, PI = Principal Investigator, 
PK = Pharmacokinetics, Preg = Pregnancy, RR = Respiratory rate, S = Screening, T = Temperature, UA = Urinalysis. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 15 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
7 
ABBREVIATIONS 
≥ 
greater than or equal to 
µ 
micro 
AE 
Adverse event 
Aet1-t2 
Amount of unchanged drug excreted in t1 to t2 urine collection interval 
ANOVA 
Analysis of variance 
AUC 
Area under the concentration-time curve 
AUC0-t 
Area under the concentration-time curve, from time 0 to the last observed 
non-zero concentration (t) 
AUC0-inf 
Area under the concentration-time curve, from time 0 extrapolated to 
infinity 
bpm 
Beats per minute 
BMI 
Body mass index 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL/F 
Apparent total plasma clearance after oral (extravascular) administration 
CLr 
Renal clearance 
Cm 
Centimeter 
Cmax 
Maximum observed concentration  
CNS 
Central nervous system 
CRF 
Case report form 
CRU 
Clinical Research Unit 
CYP 
Cytochrome P450 
DRF 
Dose range finding 
ECG 
Electrocardiogram 
%Fe 
Fraction of drug excreted unchanged in urine 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B surface antigen 
hERG 
Human ether-a-go-go related gene 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
HCV 
Hepatitis C virus 
HED 
Human equivalent dose 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IB 
Investigator’s Brochure 
IC50 
Half-maximal inhibitory concentration of enzyme activity 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
Kel 
Apparent terminal elimination rate constant 
kg 
Kilogram 
LH 
Luteinizing hormone 
ln 
Natural log 
LSM 
Least-squares means 
m2 
Meters squared 
MedDRA® 
Medical Dictionary for Regulatory Activities® 
mg 
Milligram 
mL 
Milliliter 
mmHg 
Millimeter of mercury 
MRSD 
Maximum recommended starting dose 
msec 
Millisecond 
n 
Sample size 
NAC 
N-acetylcysteine 
No. 
Number 
NOAEL 
No observed adverse effect level 
OATP 
Organic anion transporting polypeptide 
oz 
Ounce 
P-gp 
P-glycoprotein 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
QA 
Quality Assurance 
QTcF 
Fridericia’s correction method 
RBC 
Red blood cell 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to reach maximum observed concentration 
TTM 
Trichotillomania 
T½ 
Apparent terminal elimination half-life 
US 
United States 
USA 
United States of America 
Vz/F 
Apparent volume of distribution during the terminal elimination phase after 
oral (extravascular) administration 
WHO 
World Health Organization 
WONCBP 
Women of non-childbearing potential 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
8 
BACKGROUND AND RATIONALE 
 
Background 
8.1
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 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 to modulate 
glutamatergic neurotransmission in the brain.  
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 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 currently being assessed for the treatment of TTM in adults. 
NAC, one of the primary metabolites of SXC-2023, has been approved for treating hepatic 
toxicity associated with acetaminophen overdose and as a mucolytic agent. In addition, NAC 
has also been shown to be a promising treatment for several psychiatric and neurological 
disorders and has been proven to be safe, even when administered at high doses. NAC has 
been shown to be effective in the treatment of TTM in a clinical trial. SXC-2023 has been 
designed to more effectively deliver NAC and cyst(e)ine to the brain. 
 
Preclinical Trials 
8.1.1
 
Pharmacology 
8.1.1.1
In a variety of preclinical rodent models, SXC-2023 was found to increase the time spent in 
the open arm of the elevated plus maze, which is used to measure anxiety (a symptom of 
many psychiatric disorders and a clear indication of CNS penetration); ameliorated 
N-methyl-D-aspartate receptor antagonist (MK-801) induced deficits in pre-pulse inhibition, 
which tests behavior that is dependent on cortical glutamatergic transmission; and 
significantly lowered the number of lever presses to self-administer cocaine, an assay 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 19 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
measuring compulsive behavior in a model of chemical addiction. These studies, coupled 
with a study using rats engineered to lack a functional cystine-glutamate antiporter 
(specifically the xCT light chain protein), suggest that SXC-2023, through activation of 
System xc
-, may provide a novel approach to reverse the deficits associated with 
glutamatergic dysfunction and heightened levels of oxidative stress implicated in the 
pathophysiology of TTM. 
 
Pharmacokinetics 
8.1.1.2
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 has been shown to distribute into red blood cells (RBCs) and the brain of rodents, 
and into the RBCs and cerebral fluid of monkeys. SXC-2023 is rapidly absorbed in all 
species following oral administration with peak plasma concentrations occurring within 
1 hour in dogs and at up to 4 hours post-dose in monkeys. In whole blood, most of the 
SXC-2023 and NAC 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 RBCs appear to be minimal when taking 
background levels into consideration. Metabolism of SXC-2023 was evaluated using rat, 
monkey and human hepatocytes. In each species, the primary metabolites were NAC and 
p-toluic acid. Another possible minor pathway of SXC-2023 metabolism includes 
deamidation followed by cysteine conjugation. 
Based on preliminary data, the parent drug and both primary metabolites appear to have 
relatively short plasma half-lives (< 6 hours). All the metabolites are polar so extensive renal 
clearance and urinary excretion is expected. 
Following in vitro studies to assess the potential of SXC-2023 to inhibit, induce, or be 
metabolized by cytochrome P450 (CYP) enzymes, it is anticipated that the likelihood of 
drug-drug interactions with SXC-2023 is minimal, with a possible exception for inhibition of 
CYP2C8 (showing half-maximal inhibitory concentration of enzyme activity [IC50] of 
570 μM). In vitro data indicates that SXC-2023 may be a substrate of organic 
anion-transporting polypeptide (OATP)1B1 and 1B3, but not of P-glycoproteins or breast 
cancer resistance protein. 
 
Toxicity 
8.1.1.3
The safety and toxicity associated with chronic treatment with SXC-2023 was evaluated in 
two species (rats and dogs) following chronic, 7- and 28-day dosing. 
In a dose range finding (DRF) study in rats, minor, SXC-2023-related effects were observed 
at both 500 and 2000 mg/kg/day dose levels that included basophilic tubule and tubule 
dilatation findings in the kidney; however, given the magnitude of the changes and/or a lack 
of microscopic correlates, coupled to similar observations in the control group, none of these 
effects in rats were considered adverse.  

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 20 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Once daily, oral administration of SXC-2023 for 28 days at 500, 1000 and 2000 mg/kg/day 
were well tolerated in both male and female rats. While non-adverse hematology 
observations and findings consistent with chronic progressive nephropathy were observed in 
this 28-day dosing study, no adverse findings were noted. Based on these findings, and 
taking into consideration the overall wellbeing of the animals, the Study Director at the 
non-clinical 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. This 
determination also takes into consideration the markedly increased exposure to p-toluic acid 
at the highest dose. 
In dogs, a 7-day DRF study demonstrated that daily oral administration of 500 mg/kg/day 
SXC-2023 by gavage for 7 days in dogs was well tolerated. However, the dose of 
2000 mg/kg/day by gavage was not tolerated, based on the unscheduled sacrifice of 2 males 
and adverse findings that included emesis/vomiting, liquid feces, which correlated with 
decreases in body weight and food consumption. Clinical pathology findings and a decrease 
in thymus weights were observed only at the 2000 mg/kg/day dose group and were consistent 
with inflammation and/or stress. Based on this DRF study in dogs, the doses selected for the 
28-day study were 250, 500 and 1200 mg/kg/day. 
SXC-2023 had no effect on survival in Beagle dogs administered doses up to 
1200 mg/kg/day for 28 days. No CNS safety or measurements of CNS excitotoxicity 
differences in neuron integrity were noted between controls and animals administered the 
highest dose of SXC-2023 (1200 mg/kg/day). Emesis/vomitus, excessive salivation, liquid 
feces, and overall loss of body weight for animals administered 1200 mg/kg/day were 
observed. Similar findings were occasionally noted in animals administered 250 mg/kg/day 
and 500 mg/kg/day, and these findings were observed in the control animals as well.  
Decreased thymus weight parameters occurred in males at all doses, statistically significantly 
different from vehicle control at doses of 250 and 1200 mg/kg/day but not 500 mg/kg/day. 
Decreased cortical lymphocytes were observed in some males and females administered 
≥ 250 mg/kg/day. Incidence of decreased cortical lymphocytes was variable, without a clear 
dose response, with minimal to slight severity in animals administered 250 or 500 mg/kg/day 
and minimal to marked severity in animals administered 1200 mg/kg/day. Given the lack of 
clinical pathology correlates and dose response, these findings in the thymus did not impact 
the function of the organ and could be attributed to stress given the emesis, weight loss and 
need for supplementation. 
Also in the high dose group, lower testis weights for males administered 1200 mg/kg/day 
were correlated with the microscopic findings of degeneration and atrophy (slight to 
moderate) of the seminiferous tubules which were considered adverse. No effects on 
seminiferous tubules or testes weight were observed in animals administered 250 mg/kg/day 
or 500 mg/kg/day. Based on these findings, the Study Director of the non-clinical 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 NOAEL to be 250 mg/kg/day. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
This also takes into consideration the potential for increased exposure with the administration 
of enteric capsules. 
Based on a pivotal Ames assay and a human peripheral blood lymphocyte chromosome 
aberration assay, SXC-2023 is considered not genotoxic. 
Refer to the Investigator’s Brochure [SXC-2023, 2017] for detailed background information 
on SXC-2023. 
 
Rationale 
8.2
 
Rationale for this Study and Study Design 
8.2.1
This clinical trial will be the first-in-human study of SXC-2023. When developing new drugs 
for clinical indications, it is necessary to collect data on the safety, tolerability, and PK in 
order to support further development of the compound as a useful clinical candidate and 
determine of dose levels and dose intervals in Phase 2 and subsequent studies. Subjects will 
be randomized to treatment to minimize assignment bias.  
The effect of food on the rate and extent of absorption of SXC-2023 will be investigated 
when the drug is administered shortly after a meal. As per the Food and Drug Administration 
(FDA) recommendations [FDA Guidance for Industry:  Food Effect Bioavailability and Fed 
Bioequivalence Studies, 2002], the test meal provided will be a high-fat / high-calorie meal. 
The washout period between doses in the FE cohort is expected to be sufficient to prevent 
carryover effects of the treatments.  
This SAD and FE study is designed to meet the objectives outlined in Section 9.1. 
 
Rationale for the Dose Selection 
8.2.2
Given the findings in the 7-day DRF and 28- day studies in rats for doses of 500, 1000, and 
2000 mg/kg/day and in the 7-day DRF and 28-day studies in dogs for doses of 250, 500, 
1000, 1200, and 2000 mg/kg/day, a 250 mg/kg/day dose in dog was determined to be the 
NOAEL and therefore selected for the calculation of maximum recommended starting dose 
(MRSD) for the study [FDA Guidance for Industry: Estimating the Maximum Safe Starting 
Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, 2005]. 
The proposed clinical starting dose, 50 mg, is 193-fold lower than the human equivalent dose 
(HED) of 9678 mg at the rat NOAEL of 1,000 mg/kg/day and 167-fold lower than the HED 
of 8333 mg at the dog NOAEL of 250 mg/kg/day NOAEL. SXC-2023 was shown to have 
CNS activity in other relevant rodent models at a dose of 10 mg/kg in rats; the corresponding 
HED is about 100 mg. 
The concentrations of both metabolites, NAC and p-toluic acid, following administration of 
50, 100, 200, and 400 mg SXC-2023 (Cohorts 1-4) were below the levels of quantification 
for all subjects at all time points, with the exception of the 4.0 hours postdose time point for 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 22 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
NAC in a single subject, and sporadic time points for p-toluic acid, deemed not sufficient to 
generate PK parameters.  
In the safety and tolerability assessments of Cohorts 1-4, a total of 33 AEs (15 AEs in 
5 subjects in Cohort 1, 1 AE in Cohort 2, 16 AEs in 4 subjects in Cohort 3, and 1 AE in 
1 subject in Cohort 4) were observed in this study to date, all of which were considered to be 
mild to moderate in severity.  In addition, no dose dependence of AEs has been observed. 
Based on the safety and tolerability profile of SXC-2023 to date, it was decided to add a dose 
level of 1600 mg (approximately 5-fold below the NOAEL of dog) to the study in 
Amendment 2. 
 
Risks and/or Benefits to Subjects 
8.3
The safety monitoring practices employed by this protocol (i.e., physical examination, vital 
signs, 12-lead ECG, clinical laboratory tests, and AE questioning) are adequate to protect the 
subjects’ safety, should detect all expected treatment-emergent AEs (TEAEs), and are 
standard for a first-in-human, SAD study.  
Subjects will be admitted to the CRU, where they will be monitored to detect AEs during the 
study and followed appropriately to ensure resolution of AEs. Sentinel dosing will be 
employed within each cohort of the study. Available blinded safety and tolerability data will 
be assessed after each dose level to determine if it is safe to escalate to the next dose level. 
PK data will also be assessed as part of the dose escalation decision for each dose level. 
The approximate volume of blood planned for collection from each subject over the course of 
the study (see Section 11.3) presents no undue risk to the subjects nor does the possibility of 
collection (for wasting to ensure clean sample) of additional blood in the event an indwelling 
cannula is utilized and the possibility of collection of additional blood for recheck of safety 
labs if deemed necessary by the PI. 
There will be no direct health benefit for study participants from receipt of study 
drug/placebo. An indirect health benefit to the healthy subjects enrolled in this study is the 
free medical tests received at screening and during the study. 
 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
9 
STUDY OBJECTIVES AND ENDPOINTS 
 
Study Objectives 
9.1
Primary: 
To assess the safety and tolerability of SXC-2023 following administration of single 
ascending doses to healthy adult subjects. 
Secondary: 
Objective 1:  To assess the PK of SXC-2023 in plasma, RBCs (if applicable), and urine 
following administration of single ascending doses to healthy adult subjects. 
Objective 2:  To compare the single-dose PK of SXC-2023 in plasma, RBCs (if applicable), 
and urine following oral administration under fed and fasting conditions. 
Objective 3:  To assess the PK of SXC-2023 primary metabolites, NAC, and p-toluic acid, as 
available, in plasma, RBCs (if applicable), and urine, following administration of a single 
dose to healthy adult subjects. 
 
Study Endpoints 
9.2
The primary endpoints of the study will be the number and severity of TEAEs following 
single doses of SXC-2023 and placebo. 
The secondary endpoints of the study are the PK parameters following SXC-2023 
administration under fasted and fed conditions.  
The PK parameters will also be computed, as appropriate: 
SXC-2023: 
• plasma:  AUC0-t, AUC0-inf, Cmax, Tmax, CL/F, Vz/F, Kel, and T½. 
• urine:  Aet1-t2, Ae0-72, CLr, and %Fe. 
• RBCs (if applicable):  AUC0-t, AUC0-inf, Cmax, Tmax, CL/F, Vz/F, Kel, and T½. 
NAC and p-toluic acid: 
• plasma:  AUC0-t, AUC0-inf, Cmax, Tmax, Kel, and T½. 
• urine:  Aet1-t2, Ae0-72, and CLr. 
• RBCs (if applicable):  AUC0-t, AUC0-inf, Cmax, Tmax, Kel, and T½. 
The effect of food on a single oral dose of SXC-2023 will be assessed by comparing AUC0-t, 
AUC0-inf, and Cmax under fed versus fasting conditions using an ANOVA. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
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CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
10 INVESTIGATIONAL PLAN 
 Overall Study Design and Plan 
10.1
This is a randomized, double-blind, placebo-controlled, SAD and FE study.  
Up to 48 healthy, adult male and female subjects are planned to be enrolled in 6 cohorts of 
8 subjects each (6 active and 2 placebo). Subjects will participate in only one cohort. 
Screening of subjects will occur within 28 days prior to dosing. 
Each cohort will include a sentinel group (1 active and 1 placebo) who will be dosed at least 
24 hours before the remaining 6 subjects (5 active and 1 placebo). Dosing of the remaining 
6 subjects will be conducted following a safety evaluation of the sentinel group by the PI, 
Medical Monitor, and Sponsor. 
In each cohort, subjects will receive a single oral dose of SXC-2023 or placebo under fasting 
conditions, with one cohort crossing over to receive the same dose of SXC-2023 or placebo 
for a second time under fed conditions. There will be a washout period of at least 7 days 
between dosing under fasting conditions and dosing under fed conditions (high-fat breakfast).  
Blood and urine samples will be collected predose through 72 hours postdose for the PK 
assessment of SXC-2023, NAC, and p-toluic acid, as appropriate. 
Dose escalation to the next dose level (i.e., next cohort) will not take place until a PI, 
Medical Monitor, and Sponsor representative have determined that adequate safety, 
tolerability, and PK plasma have been demonstrated regarding the previous cohort(s) to 
permit proceeding to the next cohort. 
The dose level (i.e., cohort) to be used for the assessment of a FE will be determined based 
on the safety, tolerability, and PK plasma evaluations of previous cohorts.  The safety and 
tolerability of the dose at least one dose level higher than the dose level selected for the FE 
cohort, may be evaluated.  
All Parts 
Safety will be monitored throughout the study by repeated clinical and laboratory 
evaluations. 
Discontinued subjects may be replaced at the discretion of the Sponsor. 
 
Confinement, Return Visits, and Follow-Up 
10.1.1
Subjects will be housed on Day -1, at the time indicated by the CRU, until after the 72-hour 
blood draw and/or end of treatment procedures on Day 4. Subjects from one cohort will be 
confined for a second, similar, period for the FE arm of the study. A subject may be required 
to remain at the CRU for longer at the discretion of the PI or designee. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 25 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
All subjects who received a dose of study drug/placebo (including subjects who terminate the 
study early) will return to the CRU approximately 7 days after the last study drug/placebo 
administration for follow-up procedures, and to determine if any AEs have occurred since the 
last study visit. 
 
Study Duration 
10.1.2
The total planned duration of subject participation is approximately 35 days from screening 
to follow-up, with CRU confinement from check-in on Day -1 to Day 4. The total planned 
duration of subject participation is approximately 42 days for subjects enrolled to receive a 
second dose under fed conditions. 
 Study Conduct 
10.2
Please see the Study Events Flow Chart for a summary of the schedule of study participation 
and procedures in Section 6. 
 
Screening 
10.2.1
Screening will begin within 28 days prior to dosing. Informed consent will be obtained at 
screening (see Section 13.1.3). Subjects will have to meet all eligibility criteria before being 
enrolled in the study (see Section 10.3). Subjects will be informed of the study restrictions 
(see Section 10.3.5). 
The following will be recorded at screening: medical history and demographic data, 
including name, sex, age, race, ethnicity, body weight (kg), height (cm), body mass index 
(BMI) (kg/m2), and history of tobacco use.  
Safety assessment will be conducted as listed in the Study Events Flow Chart (Section 6). 
 
Check-in Procedures (Day -1) 
10.2.2
At check-in (Day -1), subjects will return to the CRU, and those subjects who satisfy all of 
the inclusion criteria and none of the exclusion criteria will qualify and be eligible for 
randomization. A check-in questionnaire will be reviewed for each subject to ensure that 
subjects remain eligible for the study since screening. Questions will focus on inclusion and 
exclusion criteria and on study restrictions. Subjects in all cohorts will be required to satisfy 
all of the inclusion criteria and none of the exclusion criteria at the time of each check-in.  
Safety assessment will be conducted as listed in the Study Events Flow Chart (Section 6). 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 26 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
Treatment Period (Day 1 to Day 4) 
10.2.3
 
Single-dose Administration 
10.2.3.1
On the morning of Day 1, predose evaluations will be obtained.   
Subjects will receive a single oral dose of the assigned formulation (SXC-2023 or placebo) 
on the morning of Day 1 (Section 10.4.1 and Section 10.4.4). 
Safety and tolerability will be monitored throughout the treatment period as listed in the 
Study Events Flow Chart (Section 6). 
Blood samples for PK assessments (Section 11.2.1) will be collected at the time points as 
listed in the Study Events Flow Chart (Section 6). 
Urine samples for PK assessments (Section 11.2.2) will be collected over specific intervals as 
listed in the Study Events Flow Chart (Section 6). 
10.2.3.1.1 Food Effect Group 
Following washout period of at least 7 days, subjects in one cohort will return and check-in 
for a second treatment period. They will receive the same treatment under fed conditions. 
The subjects will repeat the events outlined above (Sections 10.2.2 to 10.2.4) and as 
delineated in the Study Events Flow Chart (Section 6). 
 
Meal Schedule 
10.2.3.2
Water (except water provided with each dosing) will be restricted 1 hour prior to and 1 hour 
after each study drug/placebo administration, but will be allowed ad libitum at all other 
times. Other fluids may be given as part of meals and snacks but will be restricted at all other 
times throughout the confinement period. 
In the fasted cohorts, subjects will fast overnight for at least 10 hours prior to study 
drug/placebo administration. On Day 1, subjects will continue the fast for at least 4 hours 
postdose. 
On Day 1 of the fed portion, subjects will be required to fast overnight for at least 10 hours 
until 30 minutes prior to their scheduled morning dose, when they will be given a high-fat 
breakfast which will be entirely consumed within 30 minutes. An example of high-fat 
breakfast would be 2 slices of buttered toast, 2 eggs fried in butter, 2 strips of bacon, 4 oz of 
hash brown potatoes, and 240 mL of whole milk [FDA Guidance for Industry:  Food Effect 
Bioavailability and Fed Bioequivalence Studies, 2002]. Subjects will fast for at least 4 hours 
following dose on this day. 
On Day 1, standard meals will be provided at approximately 4 and 9 hours postdose, and at 
appropriate times thereafter. Snacks will be provided appropriate times thereafter. When 
confined in the CRU, subjects will be required to fast from all food and drink except water 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 27 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
between meals and snacks. 
Each meal and/or snacks served at the CRU will be standardized and will be similar in 
caloric content and composition (except for the high-fat breakfast served as part of the fed 
portion) and will be taken at approximately the same time in each period. 
 
Activity 
10.2.3.3
Subjects will remain ambulatory or seated upright for the first 4 hours following study 
drug/placebo administration, except when they are supine or semi-reclined for study 
procedures.  
However, should AEs occur at any time, subjects may be placed in an appropriate position or 
will be permitted to lie down on their right side. 
Specific measures will be taken to prevent the subject from missing a urine collection by 
strictly controlling and providing access to designated restrooms only. Subjects will be asked 
to void prior to entering the shower. 
Subjects will be instructed to refrain from strenuous physical activity which could cause 
muscle aches or injury, including contact sports at any time from screening until completion 
of the study. 
 
End-of-Treatment  
10.2.4
Subjects will remain confined until 72 hours after Day 1 dosing. Before leaving the CRU, all 
subjects will have the end-of-treatment evaluation. A subject may be required to remain at 
the CRU longer at the discretion of the PI. 
The end-of-treatment procedures are listed in the Study Events Flow Chart (Section 6). 
 
Follow-up Visit / End-of-Study  
10.2.5
All subjects who received a dose of study drug/placebo (including subjects who termination 
the study early) will be asked to return to the clinical facility for a follow-up visit 
approximately 7 days after Day 1 dosing. 
For any subject enrolled in the study, the study participation will be concluded following the 
end-of-study evaluation (approximately 7 days after the last dose) or at early termination. 
Should any subjects withdraw or be withdrawn from the study, all the follow-up 
(end-of-study) evaluations should be performed if possible, including samples for PK 
assessments if applicable. 
The follow-up (end-of-study) procedures are listed in the Study Events Flow Chart 
(Section 6). 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 28 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
Scheduled End of Study 
10.2.6
The end of the study is scheduled after completion of the evaluations in the 5 cohorts or after 
dose-limiting clinical safety endpoints have been reached to preclude further increases of 
dose. 
This time period may change in the event that the study is terminated early, additional 
cohorts are enrolled, additional time is required to review safety data between cohorts, or a 
decision is made to complete an unscheduled analysis between cohorts. 
 Selection of Study Population 
10.3
 
Number of Subjects 
10.3.1
Up to 48 healthy, adult male and female subjects will be enrolled in 6 cohorts of 8 subjects 
each (6 subjects to receive active drug and 2 subjects to receive placebo per the 
randomization)  
Every attempt will be made to enroll 50% of each sex in each cohort. 
A sentinel group (1 active and 1 placebo) in each fasted cohort will consist of 2 subjects who 
will be randomized to receive active drug or placebo. The remaining 6 subjects in the cohort 
will be randomized to receive active drug (n=5) or placebo (n=1). 
Additional subjects may be enrolled if it is deemed appropriate by the PI, the Sponsor, and 
the Medical Monitor to repeat a dose level or to study an intermediate dose level (lower than 
those planned). 
 
Inclusion Criteria 
10.3.2
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in 
the study, unless otherwise specified: 
1. Healthy, adult, male or female (WONCBP only), 18-55 years of age, inclusive, at 
screening. 
2. Continuous non-smoker who has not used nicotine-containing products for at least 
3 months prior to the first dose and throughout the study. 
3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening. 
4. Medically healthy with no clinically significant medical history, physical examination, 
laboratory profiles (including coagulation), vital signs, or ECGs, as deemed by the PI or 
designee. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 29 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
5. 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 and FSH 
serum levels consistent with postmenopausal status. 
6. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain 
from sexual intercourse during the study until 90 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 dosing of study drug/placebo. 
A male who has been vasectomized less than 4 months prior to study dosing must follow 
the same restrictions as a non-vasectomized male). 
7. If male, must agree not to donate sperm from the first dose until 90 days after the last 
dose administration. 
8. For subjects in Cohorts 5 and 6, must be able to swallow multiple capsules. 
9. Understands the study procedures in the informed consent form (ICF), and be willing and 
able to comply with the protocol. 
 
Exclusion Criteria 
10.3.3
Subjects must not be enrolled in the study if they meet any of the following criteria: 
1. Subject is mentally or legally incapacitated or has significant emotional problems at the 
time of the screening visit or expected during the conduct of the study. 
2. History or presence of clinically significant medical or psychiatric condition or disease in 
the opinion of the PI or designee. 
3. History of any illness 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. 
4. History or presence of alcoholism or drug abuse within the past 2 years prior to the first 
dose. 
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or 
related compounds. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 30 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
6. Allergy to band aids, adhesive dressing, or medical tape. 
7. Female subject of childbearing potential. 
8. Female subject with a positive pregnancy test or who is lactating. 
9. Positive urine cotinine at screening. 
10. Positive urine drug or alcohol results at screening or check-in.  
11. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg) or hepatitis C virus (HCV). 
12. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at 
screening. 
13. QTcF interval is >460 msec (males) or >470 msec (females) or has ECG findings deemed 
abnormal with clinical significance by the PI or designee at screening. 
14. Unable to refrain from or anticipates the use of any drug, including prescription and 
non-prescription medications, herbal remedies, or vitamin supplements beginning 
14 days prior to the first dose and throughout the study. After randomization/dosing, 
acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or 
designee. 
15. Is lactose intolerant. 
16. Has been on a diet incompatible with the on-study diet, in the opinion of the PI or 
designee, within the 30 days prior to the first dose and throughout the study. 
17. Donation of blood or significant blood loss within 56 days prior to the first dose. 
18. Plasma donation within 7 days prior to the first dose. 
19. Participation in another clinical study within 30 days prior to the first dose. 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 first dose of the current study. 
 
Early Termination of Subjects from the Study 
10.3.4
Subject participation in this trial may be discontinued for any of the following reasons: 
• Occurrence of any medical condition or circumstance that exposes the subject to 
substantial risk and/or does not allow the subject to adhere to the requirements of the 
protocol. 
• Any SAE, clinically significant AE, severe laboratory abnormality, intercurrent illness, or 
other medical condition that indicates to the PI that continued participation is not in the 
best interest of the subject. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 31 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
• Subject's decision to withdraw. 
• Requirement of prohibited concomitant medication. 
• Subject failure to comply with protocol requirements or study related procedures. 
• Termination of the study by the Sponsor, FDA, Celerion, or other regulatory authorities. 
The clinical report will include reason(s) for subject withdrawals as well as details relevant to 
the subject withdrawal. If a subject is withdrawn from the trial prior to study completion, the 
subject will undergo all procedures scheduled for study completion (end-of-treatment / early 
termination evaluations) as the situation allows (see Section 10.2.4). Any subject withdrawn 
due to an AE (whether serious or non-serious) or clinically significant abnormal laboratory 
test values will be evaluated by the PI or a monitoring physician and will be treated and/or 
followed up until the symptoms or values return to normal or acceptable levels, as judged by 
the PI. 
 
Prohibitions and Concomitant Medication 
10.3.5
Consumption of foods and beverages containing the following substances will be prohibited 
as indicated: 
• Xanthines/Caffeine:  24 hours before dosing and throughout the study. Subjects in the 
FE portion will be allowed to consume xanthines/caffeine containing food and 
beverages from the end of sample collection in the fasted cohort and through 24 hours 
before the second dosing (under fed conditions); 
• Alcohol:  48 hours before dosing and throughout the study. Subjects in the FE portion 
will be allowed to consume alcohol from the end of sample collection in the fasted 
cohort and through 48 hours before the second dosing (under fed conditions); 
• Grapefruit/Seville orange:  14 days before dosing and throughout the study. Subjects 
in the FE portion will be allowed to consume Grapefruit/Seville orange from the end 
of sample collection in the fasted cohort and through 14 days before the second 
dosing (under fed conditions). 
Concomitant medication will be prohibited as listed in the exclusion criteria in 
Section 10.3.3. After randomization/dosing, acetaminophen (up to 2 g per 24 hours) may be 
administered at the discretion of the PI or designee. 
If deviations occur, the PI or designee in consultation with the Sponsor will decide on a 
case-by-case basis whether the subject may continue participation in the study. 
All medications taken by subjects during the course of the study will be recorded. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 32 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 Treatments 
10.4
 
Treatments Administered 
10.4.1
SXC-2023 will be supplied as 50 and 200 mg capsules. 
Placebo will be provided as matching placebo capsules. 
Subjects will be instructed not to crush, split or chew the study drug/placebo. 
Subjects in each cohort will receive a single oral dose of SXC-2023 or placebo, under fasting 
conditions. 
Planned doses will be as follows: 
Cohort 1:  50 mg (1 x 50 mg capsule) SXC-2023 or matching placebo 
Cohort 2:  100 mg (2 x 50 mg capsules) SXC-2023 or matching placebo 
Cohort 3:  200 mg (1 x 200 mg capsule) SXC-2023 or matching placebo 
Cohort 4: 400 mg (2 x 200 mg capsules) SXC-2023 or matching placebo 
Cohort 5: 800 mg (4 x 200 mg capsules) SXC-2023 or matching placebo 
Cohort 6: 1600 mg (8 x 200 mg capsules) SXC-2023 or matching placebo 
One cohort will receive the same dose of SXC-2023 or placebo for a second time under fed 
conditions following a washout period of at least 7 days. The dose level (i.e., cohort) to be 
used for the FE cohort will be determined based on the safety, tolerability, and PK plasma 
evaluations of previous cohorts and the safety. The safety and tolerability of the dose at least 
one dose level higher than the dose level selected for the FE cohort, may be evaluated. 
When administered under fed conditions, SXC-2023 will be administered orally following a 
high-fat breakfast. 
A sentinel group (1 active and 1 placebo) in each fasted cohort will consist of 2 subjects who 
will be randomized to receive active drug or placebo. The remaining 6 subjects in the cohort 
will be randomized to receive active drug (n=5) or placebo (n=1). 
All doses of study drug/placebo will be administered with approximately 240 mL of water. In 
Cohort 6, if the study drugs cannot all be swallowed at the same time, the drug administration 
may be divided; however, dosing should be completed within 10 minutes. Additional water, 
up to a maximum of 50 mL may be administered as required by the subject. 
An unblinded pharmacist will be responsible for providing SXC-2023 or placebo to the 
blinded study personnel for administration. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 33 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
The exact clock time of dosing will be recorded. 
 
Repeat / Additional Dose Levels 
10.4.2
Additional subjects may be enrolled if it is deemed appropriate by the PI, the Sponsor, and 
the Medical Monitor to repeat a dose level or to study an intermediate dose level (lower than 
those planned). 
 
Dose Escalation and Stopping Rules 
10.4.3
A decision to proceed to the next higher dose administration will be made by the safety data 
review team which includes but is not limited to, the following members:  the PI, Medical 
Monitor, and Sponsor representative. The safety data review team will review all pertinent 
blinded safety/tolerability (e.g., physical examinations, vital signs assessments, ECGs, 
clinical laboratory tests, and AEs) and PK plasma data through at least 3 days following 
Day 1 dosing for at least 75% of subjects of the current dose level cohort and those from all 
previous cohorts. The safety data review team will make one of the following determinations: 
• To continue with the study as planned. 
• To continue with the study and add additional safety evaluations. 
• To continue with the study by repeating the current dose, adjusting to an intermediate 
dose between the current dose and the next planned dose, or adjusting to an intermediate 
dose between the current dose and the previous lower dose if 1 subject at a given dose 
level meets any of the following criteria and the subject was determined, after unblinding, 
to have received active drug: 
 Has a drug-related SAE (see Section 11.1.6.4). 
 Experiences drug-related grade ≥3 severity AE (see Section 11.1.6.3). 
• To terminate the study if ≥2 subjects in a cohort meet any of the following criteria and 
the subjects were determined, after unblinding, to have received active drug: 
 Have a drug-related SAE (see Section 11.1.6.4). 
 Experience drug-related grade ≥3 severity AE (see Section 11.1.6.3). 
When applicable, a written statement fully documenting the reasons for study termination 
will be provided to the institutional review board (IRB). 
 
Method of Assigning Subjects to Treatment Groups 
10.4.4
Each subject will be assigned a unique identification number upon screening. Subjects who 
complete the study screening assessments and meet all the eligibility criteria will be assigned 
a unique randomization identification number at the time of dosing, different from the 
screening number, and will receive the corresponding dose of study drug/placebo, according 
to a randomization scheme generated at Celerion.  

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 34 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Subjects will participate in only one cohort (in one selected cohort, subjects will participate 
in the fasted portion and the fed portion).  
Subjects will be randomized to receive either SXC-2023 or placebo, maintaining a 3:1 ratio 
in each cohort. Attempts will be made to enroll 50% of each sex in each cohort. 
In each cohort, a sentinel group will consist of 2 subjects who will be randomized to receive 
active drug or placebo (1 active and 1 placebo). The remaining 6 subjects in the cohort will 
be randomized to receive active drug (n=5) or placebo (n=1). 
Subjects in the first enrollment cohort will be numbered 1001 – 1008; subjects in the second 
enrollment cohort will be numbered 2001 – 2008, etc.  
If replacement subjects are used, they will be assigned a number 100 higher than the original 
subject (e.g., Subject 1106 would replace Subject 1006). A second replacement for a subject 
will be assigned a number 100 higher than prior replacement subject (e.g., Subject 1206 
would replace Subject 1106). 
 
Blinding 
10.4.5
This is a double-blind, randomized, placebo controlled study. 
 
Maintenance of Randomization 
10.4.5.1
A computerized randomization scheme will be created by a Celerion statistician and it shall 
be considered blinded (as per the following).  
The randomization is available only to the clinic pharmacy staff that is preparing the drug 
who will not be involved in any other aspect of the study including administration of the 
drug. It will not be made available to the Sponsor, bioanalytical laboratory, subjects, or 
members of the staff responsible for the monitoring and evaluation of safety assessments. 
 
Procedures for Breaking the Blind Prior to Study Completion 
10.4.5.2
One set of sealed envelopes containing the randomization code will be supplied to the PI or 
designee at the start of the study. 
Breaking of the blind is expressly forbidden except in the event of a medical emergency 
where the identity of the drug must be known in order to properly treat the subject or in the 
event of an interim analysis.  
In the event of a medical emergency, it is requested that the PI or designee make every effort 
to contact the Study Monitor or designee prior to breaking the blind. If breaking the blind is 
required because of a medical emergency, the treatment identity would be revealed by the PI 
or designee, for that subject only. In the event that the emergency is one, in which it appears 
that the other subjects may be at imminent risk, the blind may be broken for all subjects 
dosed at that dose level. The unblinding will be properly documented in the study file. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 35 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
In all cases where the blind is broken, the PI or designee should record the date and reason 
for blind breaking. 
At the end of the study, envelopes will be retained or destroyed according to site procedures 
unless specified otherwise by the Sponsor. 
 
Revealing of Randomization 
10.4.5.3
In the absence of a medical emergency, the blinded randomization for this study will not be 
revealed until all data are entered in the database, edits checks are performed, queries closed, 
and the database is officially locked. 
 Interim Analysis 
10.4.5.4
Safety: 
All available blinded safety data will be reviewed by the PI, Medical Monitor, and Sponsor 
representative prior to dose escalation and to determine the dose level for the FE cohort. 
At the Sponsor’s request, unblinded safety tables, figures, and data listings may be presented 
to the Sponsor for the purposes of planning the next clinical studies prior to database lock. 
These interim analyses will be performed on data that will be edit-checked and monitored. 
A safety data analyst and a biostatistician at Celerion who are not involved with the present 
study and are not located at the Celerion’s Phoenix site will be unblinded to prepare 
unblinded safety tables, figures, and data listings, if needed. All the personnel related to the 
present study will remain blinded. 
Pharmacokinetics:  
Preliminary PK analysis will be performed for all cohorts. PK plasma analysis data will be 
used to guide the dose escalation decision and may be used to evaluate the sampling time 
points as the study progresses. PK plasma analysis data will also be used to determine the 
dose level for the FE cohort. 
Interim PK analysis will not use the actual subject numbers in order to avoid breaking the 
blind. 
 
Treatment Compliance  
10.4.6
A qualified designee will be responsible for monitoring the administration of the timed oral 
doses. A mouth check will be performed by the qualified designee to ensure that the subjects 
have swallowed the study drug/placebo. Once a subject has finished the dosing water, the 
qualified designee will use a flashlight and a tongue depressor to check the subject’s mouth. 
Subjects’ hands will also be verified to ensure that the study drug/placebo was ingested. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 36 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
11 STUDY PROCEDURES 
 Safety Assessments 
11.1
The Study Events Flow Chart (Section 6) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. 
Additional evaluations/testing may be deemed necessary by the PI or designee and/or the 
Sponsor for reasons related to subject safety. 
For this study, the primary assessment is the safety and tolerability. Safety will be determined 
by evaluating physical examinations, vital signs, 12-lead ECGs, clinical laboratory 
parameters, including but not limited to, hematology, clinical chemistry profile, urinalysis, 
and AEs as outlined in the Study Events Flow Chart (Section 6). 
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 
 
Body Height and Weight 
11.1.1
Body height (centimeters) and body weight (kilograms) will be measured as outlined in the 
Study Events Flow Chart (Section 6). BMI will be calculated. 
 
Physical Examination 
11.1.2
A full physical examination will be performed as per Study Events Flow Chart (Section 6). 
Symptom-driven physical examinations may be performed at other times, if deemed 
necessary by the PI or designee. 
 
Vital Signs 
11.1.3
Single measurements of body temperature, respiratory rate, blood pressure and heart rate, 
will be measured as outlined in the Study Events Flow Chart (Section 6). Additional vital 
signs may be taken at any other times, if deemed necessary. 
Blood pressure and heart rate measurements will be performed with subjects in a seated 
position, except when they are supine or semi-reclined because of study procedures and/or 
AEs (e.g. nausea, dizziness) or if deemed necessary by the PI or designee. 
Vital signs will be measured within 24 hours prior to dosing on Day 1, for the predose time 
point. When scheduled postdose, vital signs will be performed within approximately 
10 minutes of the scheduled time point. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 37 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
12-Lead ECG Monitoring 
11.1.4
ECGs will be performed as outlined in the Study Events Flow Chart (Section 6). 
ECGs will be measured within 24 hours prior to dosing on Day 1, for each cohort for the 
predose time point. When scheduled postdose, ECGs will be performed within approximately 
20 minutes of the scheduled time point. 
ECGs will be taken following resting in the supine position in a quiet environment. Single 
12-lead ECGs may be taken at any other times, if deemed necessary.  
All ECGs will be interpreted on-site by the PI or designee. 
A subject will be withdrawn 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. 
 
 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 38 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
Clinical Laboratory Tests 
11.1.5
All tests listed below will be performed as per Study Events Flow Chart (Section 6). In 
addition, laboratory safety tests may be performed at various unscheduled time points, if 
deemed necessary by the PI or designee. 
Hematology 
 
Serum Chemistry* 
• 
Hemoglobin 
• 
Hematocrit  
• 
Mean corpuscular volume 
• 
Mean corpuscular hemoglobin 
• 
Mean corpuscular hemoglobin concentration 
• 
Total and differential leukocyte count 
• 
RBC count 
• 
Platelet count 
 
 
• 
Blood Urea Nitrogen 
• 
Bilirubin (total and direct) 
• 
Alkaline phosphatase 
• 
Aspartate aminotransferase 
• 
Alanine aminotransferase 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Glucose (fasting) 
• 
Creatinine** 
• 
Creatine phosphokinase 
• 
Gamma-glutamyl transferase 
Coagulation 
• 
Prothrombin time / International normalized ratio, 
and activated prothrombin time 
 
Urinalysis 
 
Additional Tests 
• 
pH 
• 
Specific gravity 
• 
Protein*** 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Blood*** 
• 
Nitrite*** 
• 
Urobilinogen 
• 
Leukocyte esterase*** 
 
• 
HIV test 
• 
HBsAg 
• 
HCV 
• 
Urine drug screen 
 Opioids 
 Opiates 
 Amphetamines 
 Barbiturates 
 Benzodiazepines 
 Cocaine 
 Cannabinoids 
• 
Urine alcohol screen 
• 
Urine cotinine 
• 
Serum pregnancy test  
(for females only) 
• 
FSH ¥ 
• 
Luteinizing hormone (LH) ¥ 
• 
Total testosterone ¥ 
 
* 
Serum chemistry tests will be performed after at least a 8-hour fast; however, in case of dropouts or 
rechecks, subjects may not have fasted for 8 hours before the serum chemistry sample is taken. 
** At screening, creatinine clearance will be calculated using the Cockcroft-Gault formula. 
*** If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination 
(for RBCs, white blood cells, bacteria, casts, and epithelial cells) will be performed. 
¥ 
Samples for serum total testosterone, LH, and FSH will be collected at the same clock time (±1 hour) in 
the morning (before 10:00 AM) on each scheduled day, except for sample for FSH collected from 
postmenapausal women at screening. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 39 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
Adverse Events  
11.1.6
 
Adverse Event Definition 
11.1.6.1
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. 
A suspected adverse reaction means any AE for which there is a reasonable possibility that 
the drug caused the AE. Reasonable possibility means there is evidence to suggest a causal 
relationship between the drug and the AE.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
 
Monitoring 
11.1.6.2
Subjects will be monitored throughout confinement for adverse reactions to the study 
formulations and/or procedures. Prior to release, subjects will be asked how they are feeling. 
At the beginning of the second period of the FE cohort subjects will be queried with an 
open-ended question such as: ‘How have you been feeling since your last visit?’  
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test 
value(s) will be evaluated by the PI or designee and treated and/or followed up until the 
symptoms or value(s) return to normal, or acceptable levels, as judged by the PI or designee.  
Treatment of serious adverse events (SAEs) will be performed by a physician, either at 
Celerion or at a nearby hospital emergency room. Where appropriate, medical test(s) and/or 
examination(s) will be performed to document resolution of event(s). Outcome may be 
classified as resolved, improved, unchanged, worse, fatal, or unknown (lost to follow-up). 
 
Reporting 
11.1.6.3
All AEs that occurred during this clinical trial will be recorded. AEs will be coded using the 
most current Medical Dictionary for Regulatory Activities (MedDRA®). 
The PI will review each event and assess its relationship to drug treatment (likely, probably, 
possibly, unlikely or unrelated). Each sign or symptom reported will be graded on the FDA 
(CBER) toxicity grading scale for healthy volunteers 4-point severity scale (Grade 1, 2, 3 and 
4) [FDA (CBER) Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, 2007]. The date and 
time of onset, time relationship to drug dosing, duration, and outcome of each event will be 
noted.  

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 40 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Relationship of AE: 
The relationship of each AE to the study drug will be assessed using the following 
definitions: 
Unrelated  The adverse event must clearly be caused by the participant’s clinical state, 
or the study procedure/conditions 
 Definitely not related to drug 
 Temporal sequence of an adverse event onset relative to administration of 
drug not reasonable 
 Another obvious cause of an adverse event 
Unlikely 
 Time sequence is unreasonable 
 There is another more likely cause for an adverse event 
Possibly 
 Corresponds to what is known about the drug 
 Time sequence is reasonable 
 Could have been due to another equally, likely cause 
Probably 
 Is a known effect of the drug 
 Time sequence from taking drug is reasonable 
 Ceases on stopping the drug 
 Cannot be reasonably explained by the known characteristics of the 
participants clinical state 
Likely 
 Is a known effect of the drug (e.g. listed in PDR, CPS, IB) 
 Time sequence from taking drug is reasonable 
 Event stops upon stopping drug, event returns upon restarting drug 
Severity of AE: 
The following definitions for rating severity will be used: 
Grade 1 
 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL*. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 41 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Grade 3  
 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self care ADL**. 
Note: An experience may be severe but may not be serious (e.g., severe 
headache). 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
A semi-colon indicates ‘or’ within the description of the grade. 
Note: Activities of Daily Living (ADL)  
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
 
Serious Adverse Event 
11.1.6.4
If any AEs are serious, as defined by the Food and Drug Administration (FDA) Code of 
Federal Regulations (CFR), Chapter 21, special procedures will be followed. All SAEs will 
be reported to the Sponsor via fax or e-mail within one working day of becoming aware of 
the event, whether or not the serious events are deemed drug-related. All serious event 
reporting will adhere to 21 CFR 312.32 for Investigational New Drugs (IND) and to the 
Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and 
BA/BE, dated December 2012. The IRB will be notified of the Alert Reports as per FDA 
regulations. 
A SAE is any AE or suspected adverse reaction that in the view of either the PI (or designee) 
or Sponsor, results in any of the following outcomes:  Death, a life-threatening adverse event, 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in the above definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse.  
Life-threatening is defined as an AE or suspected adverse reaction that in the view of the PI 
(or designee) or Sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred 
in a more severe form, might have caused death. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 42 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Unexpected is defined as an AE or suspected adverse reaction that is not listed in the IB or is 
not listed at the specificity or severity that has been observed; or is not consistent with the 
risk information described in the general investigational plan or elsewhere in the current 
application, as amended. 
If a SAE occurs to a subject on this study, contact the Sponsor personnel listed in Section 3. 
 Pharmacokinetic Assessments 
11.2
 
Blood Sampling and Processing 
11.2.1
As a precaution, blood samples will be collected and processed under conditions that will 
minimize their exposure to UV light. 
For all subjects, blood samples for the determination of SXC-2023, NAC, and p-toluic acid 
will be collected in blood collection tubes at scheduled time points as delineated in the Study 
Events Flow Chart (Section 6).  For doses ≥ 200 mg, RBCs will be collected to assess 
analytes, if appropriate. 
Instruction for blood sampling, collection, processing, and sample shipment will be provided 
separately. 
The allowable deviation window is as follows: 
Sample time 
Allowed deviation 
≤ 8.0 hours 
± 2 minutes 
> 8.0 hours to ≤ 24 hours 
± 5 minutes 
> 24 hours to ≤ 72 hours 
± 10 minutes 
> 72 hours 
± 15 minutes 
 
Urine Sampling and Processing 
11.2.2
As a precaution, samples will be collected and processed under conditions that will minimize 
their exposure to UV light. 
Urine for PK assessments will be collected at the specified intervals delineated in the Study 
Events Flow Chart (Section 6). 
Prior to the predose sample, each subject will be instructed as to urine collection methods. 
All urine during an interval is to be collected.  
On Day 1, a spot collection will be obtained prior to dosing for the predose sample. Subjects 
will be asked again to empty their bladder within approximately 15 minutes prior to dosing, 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 43 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
and no urine will be collected at this time unless it is needed for the predose sample. Only 
one predose urine sample will be collected on Day 1. 
Subjects will be encouraged to void at the end of each collection interval. If they do void at 
any time during the collection interval, the time should be documented. Should this be the 
case, subjects need to void again at the end of the collection period, as scheduled. However, 
should subjects be unable to void, this will be documented as well.  
Urine will be refrigerated during the collection intervals. At the end of each interval, urine 
will be pooled and thoroughly mixed. Total urine volume will be weighed and recorded.  
Instructions for urine sampling, collection, processing, and sample shipment will be provided 
separately document. 
 
Analytical Method 
11.2.3
Samples will be analyzed for SXC-2023, NAC, and p-toluic acid in plasma and urine using 
validated bioanalytical methods and samples for one or more analytes, if applicable, in RBCs 
will be analyzed using qualified bioanalytical methods.  Samples from subjects to be assayed 
are specified in Section 12.2.2. 
 Blood Volume Drawn for Study Assessments 
11.3
Table 1: Blood Volume during the Study 
Sample Type 
Number of 
Time Points 
Approximate 
Volume per Time 
Point (mL) 
Approximate Sample 
Volume Over Course of 
Study (mL) 
Screening laboratory safety tests 
(including hematology, serum chemistry, 
coagulation, and serology), FSH (for 
postmenopausal female subjects only), and 
serum pregnancy (for female subjects 
only). 
1 
16 
16 
On-study hematology and serum chemistry 
(this includes serum pregnancy for female 
subjects only and testosterone, LH, and 
FSH, when scheduled at the same time) 
3 (6 **) 
12.5 
37.5 (75 **) 
Blood for SXC-2023, NAC, and p-toluic  
18 (36 **) 
4 
72 (144 **) 
Total Blood Volume (mL)→ 
125.5 (235 **) * 
* 
If additional safety, and/or PK analysis is necessary or if larger collection tubes are required to obtain 
sufficient plasma/serum and/or RBCs for analysis, additional blood may be obtained (up to a maximum of 
50 mL). 
** 
Subjects in the FE cohort. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 44 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
12 DATA ANALYSIS 
Data will be handled and processed according to Celerion Standard Operating Procedures, 
which are written based on the principles of GCP. 
 Pharmacokinetic Parameters 
12.1
 
For Plasma and Red Blood Cells 
12.1.1
PK parameters for plasma and RBCs (if applicable) SXC-2023, NAC, and p-toluic will be 
calculated as follows, as appropriate: 
AUC0-t: 
 
The area under the concentration-time curve, from time 0 to the last observed 
non-zero concentration, as calculated by the linear trapezoidal method. 
AUC0-inf: 
The area under the concentration-time curve from time 0 extrapolated to 
infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the 
last measurable plasma and RBC concentration to the elimination rate 
constant. 
CL/F: 
Apparent total plasma and RBC clearance after oral (extravascular) 
administration, calculated as Dose/AUC0-inf (parent only). 
Cmax: 
Maximum observed concentration. 
Tmax: 
Time to reach Cmax. If the maximum value occurs at more than one time 
point, Tmax is defined as the first time point with this value. 
Kel: 
Apparent first-order terminal elimination rate constant calculated from a 
semi-log plot of the plasma and RBC concentration versus time curve. The 
parameter will be calculated by linear least-squares regression analysis using 
the maximum number of points in the terminal log-linear phase (e.g., three or 
more non-zero plasma/RBC concentrations). 
T½: 
Apparent first-order terminal elimination half-life will be calculated as 
0.693/Kel. 
Vz/F: 
Apparent volume of distribution during the terminal elimination phase after 
oral (extravascular) administration, calculated as Dose/(AUC0-inf x Kel) 
(parent only). 
No value for AUC0-inf, CL/F, Vz/F, Kel, or T½ will be reported for cases that do not exhibit 
a terminal log-linear phase in the concentration-time profile. 
Individual and mean plasma and RBC (if applicable) concentration time curves (both linear 
and log-linear) will be included in the final report. 
Additional PK parameters may be calculated, if deemed appropriate. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 45 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 
For Urine 
12.1.2
PK parameters for urine SXC-2023, NAC, and p-toluic will be calculated as follows: 
Aet1-t2 
Amount of drug excreted in the urine collection interval from t1 to t2. 
Ae0-72: 
Total amount of drug excreted in the urine over the entire period of sample 
collection (0-72 h), obtained by adding the amounts excreted over each 
collection interval.  
CLr: 
Renal clearance calculated as Ae(t’-t”)/AUC(t’-t”) where t’-t” is the longest 
interval of time during which Ae and AUC are both obtained.  
%Fe 
Fraction of drug excreted unchanged in urine (parent only) 
Additional PK parameters may be calculated if deemed appropriate. 
 Statistical Methods 
12.2
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 by 
Celerion and agreed upon with the Sponsor. This document may modify the plans outlined in 
the protocol; however, any major modifications of the primary endpoints definition and/or its 
analysis will also be reflected in a protocol amendment. Additional statistical analyses other 
than those described in this section may be performed if deemed appropriate.  
 
Determination of Sample Size 
12.2.1
The sample size chosen for this study has been determined adequate to meet the study 
objectives. 
 
Subjects to Analyze 
12.2.2
Safety Population: All subjects who received any dose of the study drug/placebo will be 
included in the safety evaluations. 
PK Population: Samples from all subjects will be assayed even if the subjects do not 
complete the study. All subjects who comply sufficiently with the protocol and display an 
evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence 
of major protocol violations) will be included in the statistical analyses. 
 
Safety Evaluation 
12.2.3
The following analyses will be performed; however, no formal inferential statistics will be 
performed on safety assessments. 
The placebo subjects from all cohorts in each part will be pooled into a single placebo group 
for all summaries and presentations. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 46 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
A by-subject TEAE data listing, including verbatim term, preferred term, treatment, severity, 
outcome, seriousness, and relationship to treatment, will be provided. 
The number of subjects experiencing AEs and number of AEs will be summarized by 
treatment using frequency counts. 
Safety data, including laboratory evaluations, vital signs assessments, and ECGs will be 
summarized by treatment and time point of collection. 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will 
be compiled for classification of qualitative safety data. 
A mean change-from-baseline table will be provided for vital signs, ECGs and clinical 
laboratory results, per treatment. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory 
results.  
A normal-abnormal shift table will be presented for ECGs. 
AEs will be coded using the most current version of MedDRA® available at Celerion. 
Concomitant medications will be listed by treatment and coded using the most current WHO 
drug dictionary available at Celerion and listed by treatment. 
 
Pharmacokinetic Analysis 
12.2.4
 
Descriptive statistics 
12.2.4.1
Values will be calculated for plasma, RBCs (if appropriate) and urine SXC-2023, NAC, and 
p-toluic concentrations following SXC-2023 administration under fasted and fed conditions, 
and the PK parameters listed in Section 12.1 using appropriate summary statistics to be fully 
outlined in the SAP. 
 
Food Effect Assessment 
12.2.4.2
An ANOVA will be performed on the natural log (ln)-transformed AUC0-t, AUC0-inf, and 
Cmax. The ANOVA model will include dietary conditions (fast, fed) as a fixed effect and 
subject as a random effect. Each ANOVA will include calculation of least-squares means 
(LSM), the difference between regimen LSM, and the standard error associated with this 
difference. The above statistical analyses will be done using the appropriate statistical 
procedure. 
Ratios of LSM will be calculated using the exponentiation of the LSM from the analyses on 
the ln-transformed AUC0-t, AUC0-inf, and Cmax. These ratios will be expressed as a 
percentage relative to the fasting conditions. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 47 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
Ninety percent (90%) confidence intervals (CIs) for the ratios will be derived by 
exponentiation of the CIs obtained for the difference between regimen LSM resulting from 
the analyses on the ln-transformed AUC0-t, AUC0-inf, and Cmax. The CIs will be expressed 
as a percentage relative to the fasting conditions. 
 
Dose Proportionality Analysis 
12.2.4.3
Dose proportionality will be evaluated for SXC-2023, NAC, and p-toluic AUC and Cmax 
parameters following administration of single doses (fasted cohorts). To evaluate dose 
proportionality, a regression approach will be used. A statistical linear relationship between 
the ln-transformed PK parameters AUC and Cmax and the ln-transformed dose will be fitted 
by using a regression model with ln-transformed dose as a covariate.  
Ln(Y) = β0 + β Ln Dose + ε (Model 1) 
where Y represents the PK parameter, AUCs and Cmax. 
This approach is usually referred to as a power model because after exponentiation: 
Y = α (Dose)β 
where α only depends on β0 and error. 
Dose proportionality requires that β = 1 for dose-dependent parameters. 
As a first step, the statistical linear relationship between the ln-transformed PK parameters 
AUC and Cmax and the ln-transformed dose will be verified by including the (ln dose)2 and 
(ln dose)3 terms in model, as applicable, which corresponds to the quadratic and cubic 
effects. A 5% level of significance will be used to test the quadratic and/or cubic effects. The 
statistical linear relationship will be concluded if the quadratic and cubic terms are not 
statistically significant or if the effects are statistically significant, but of small magnitude 
(not clinically relevant). If the statistical linear relationship is established in step 1, a second 
step will be performed. As a second step, model will be used to calculate the 95% CIs for the 
slope of the ln-transformed PK parameters, AUC and Cmax. 
Dose proportionality will be established if a statistical linear relationship is demonstrated and 
if the 95% CIs for these parameters include the value of 1 for dose-dependent parameters 
(AUC and Cmax). The above assessments of dose proportionality will be performed using 
the SAS® mixed procedure. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 48 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
13 STUDY ADMINISTRATION 
 Ethics 
13.1
 
Institutional Review Board 
13.1.1
This protocol will be reviewed by the Chesapeake Research Review, Inc. 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 
US Code of Federal Regulations (21 CFR Part 56). The IRB is compliant to International 
Council for Harmonisation (ICH) guidelines, and may be reached at: 
Chesapeake IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, Maryland 21046, USA 
Tel.:  +1 410 884-2900 
 
Ethical Conduct of the Study 
13.1.2
This research will be carried out in accordance with the protocol, US Code of Federal 
Regulations, 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). 
 
Subject Information and Consent 
13.1.3
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 ICF 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 ICF. 
 Termination of the Study 
13.2
Celerion reserves the right to terminate the study in the interest of subject welfare. 
 Data Quality Assurance 
13.3
Standard operating procedures are available for all activities performed at Celerion relevant 
to the quality of this study. Designated personnel of Celerion 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. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 49 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
The Clinical Study Report will be audited by the QA department and the QA audit certificate 
will be included in the study report. 
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. 
 Direct Access to Source Data/Documents 
13.4
Celerion 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. 
 Drug Supplies, Packaging and Labeling 
13.5
The Sponsor will supply sufficient quantities of the study formulations and matching placebo 
to allow completion of this study. The lot numbers and expiration dates (where available) of 
the study drugs/placebo supplied will be recorded in the final report. 
Records will be made of the receipt and dispensing of the study drugs supplied. At the 
conclusion of the study, any unused study drugs/placebo will be retained by Celerion, 
returned to the Sponsor or designee, or destroyed, as per Sponsor instructions. If no supplies 
remain, this fact will be documented in the pharmacy product accountability records. 
 Data Handling and Record Keeping 
13.6
Celerion 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 Celerion 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. 
 
Report Format 
13.7
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).  

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 50 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
 Publication Policy 
13.8
All unpublished information given to Celerion 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. 

SXC-2023 
SAD and FE Study Protocol, Amendment 2 
Promentis Pharmaceuticals, Inc. 
Sponsor Project No.:  PRO-101 
Celerion Project No.:  CA22427 
US Pre-IND No.:  133689 
 
Page 51 
CA22427 (PRO-101)_Final_Amendment 2_Protocol_05Jan2018 
14 REFERENCES 
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Robbins TW, Bullmore ET, Sahakian BJ. Grey matter abnormalities in trichotillomania: 
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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. 
Grant JE and Chamberlain SR. Trichotillomania. The American Journal of Psychiatry, 
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Grant JE, Odlaug BL, and Kim SW. N-acetylcysteine, a glutamate modulator, in the 
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http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-afda-
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quivalent+dose&aqs=chrome.1.69i57j0l3.9383j0j7&sourceid=chrome&ie=UTF-8. Accessed 
on: May-2017. 
FDA (CBER) Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. September 2007. 
Available online at:  https://www.fda.gov/biologicsbloodvaccines/guidancecompliance 
regulatoryinformation/guidances/vaccines/ucm074775.htm Accessed on: May-2017. 
Investigator’s Brochure for SXC-2023, Edition 1, Promentis Pharmacauticals, Inc., Jun-2017. 
Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies 
revisited. FASEB J. 2008;22(3):659-61. 
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. Behavioural Brain Research. 2015; 279: 255-258.