Clinical trial NCT03301298
Conditions: Healthy
Sponsor: Promentis Pharmaceuticals, Inc.
Start date: 2017-09-11; Completion date: 2018-02-13
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blind, placebo-controlled, single ascending oral dose and food effect study conducted at one study center in the United States. Safety and tolerability will be assessed throughout the study and serial blood samples and urine samples will be collected for the safety and pharmacokinetic assessment of SXC-2023.

Detailed description:

Arms: arm 1: Single dose of 50 mg, given orally in capsule form. arm 2: Single dose of 100 mg, given orally in capsule form. arm 3: Single dose of 200mg, given orally in capsule form. arm 4: Single dose of 400mg, given orally in capsule form. arm 5: Single dose of 800mg, given orally in capsule form. arm 6: Single dose of 1600 mg, given orally in capsule form. arm 7: Placebo comparator, given once orally in matching capsule form.
Interventions: intervention 1: SXC-2023 intervention 2: Placebo oral capsule
Intervention descriptions: intervention 1: Oral capsule intervention 2: Placebo given as oral capsule.

Protocol documents:
Prot_001.pdf: 
 
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 
 
Page 18 
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 
 
Page 21 
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 
 
Page 24 
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 
Chamberlain SR, Menzies LA, Fineberg NA, Del Campo N, Suckling J, Craig K, Müller U, 
Robbins TW, Bullmore ET, Sahakian BJ. Grey matter abnormalities in trichotillomania: 
morphometric magnetic resonance imaging study. Br J Psychiatry.2008;193(3):216-21.  
Chamberlain SR, Hampshire A, Menzies LA, Garyfallidis E, Grant JE, Odlaug BL et al. 
Reduced brain white matter integrity in trichotillomania: a diffusion tensor imaging study. 
Arch Gen Psychiatry 2010;67: 965–971. 
Grant JE and Chamberlain SR. Trichotillomania. The American Journal of Psychiatry, 
2016;173 (9), 868-874.  
Grant JE, Odlaug BL, and Kim SW. N-acetylcysteine, a glutamate modulator, in the 
treatment of trichotillomania. Arch Gen Psychiatry. 2009;66(7):756-763.  
FDA, Center for Drug Evaluation and Research (CDER). Guidance for Industry:  
Food-Effect Bioavailability and Fed Bioequivalence Studies (Dec 2002). Available at:  
http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-afda-
gen/documents/document/ucm126833.pdf, accessed on:  May-2017. 
FDA Guidance to Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical 
Trials for Therapeutics in Adult Healthy Volunteers (Jul 2005), Available at: 
https://www.google.ca/search?q=fda+guidance+human+equivalent+dose&oq=fda+human+e
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. 

SAP_000.pdf: 
Statistical Analysis Plan 
 
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 
 
Protocol No: PRO-101 
Final Protocol Date: 17 July 2017 
Amendment #1 Date: 02 November 2017 
Amendment #2 Date:  05 January 2018 
Compound Name: SXC-2023 
 
 
 
Celerion Project CA22427 
Draft Version 1.0 
Date: 28 February 2018 
Promentis Pharmaceuticals, Inc. 
 826 North Plankinton Avenue, Suite 400 
Milwaukee, Wisconsin 53203, USA 
 
Celerion 
2420 West Baseline Road 
Tempe, Arizona 85283, USA 
100 Alexis-Nihon Boulevard, Suite 360, Montreal, QC, H4M 2N8, Canada  


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 2 of 105 
Statistical Analysis Plan Signature Page 
Compound Name: SXC-2023 
Protocol: PRO-101 
Study Title: 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 
Issue Date: 28 February 2018 
Signature:_____________________________________ 
Date:_______________ 
Sanyath Radji, MS 
Biostatistician, Data Management and Biometrics 
Celerion, Montreal, Quebec, Canada  
Signature:_____________________________________ 
Date:_______________ 
Joelle Batonga, MSc 
Senior PK Scientist I, Clinical Pharmacology and Pharmacometrics, 
Data Management and Biometrics 
Celerion, Montreal, Quebec, Canada 
Signature:_____________________________________ 
Date:_______________ 
Thomas Beck, MD 
Chief Medical Officer 
Promentis Pharmaceuticals, Inc. 
Signature:_____________________________________ 
Date:_______________ 
Chad Beyer, PhD MBA 
Senior Vice President, Research and Development 
Promentis Pharmaceuticals, Inc.


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 3 of 105 
Table of Contents 
1. 
INTRODUCTION ..............................................................................................................5 
2. 
OBJECTIVES AND ENDPOINTS ....................................................................................5 
2.1 
Objectives ..................................................................................................................5 
2.2 
Endpoints ..................................................................................................................5 
3. 
STUDY DESIGN ...............................................................................................................6 
4. 
ANALYSIS POPULATIONS ............................................................................................7 
4.1 
Analysis Populations .................................................................................................7 
4.2 
Preliminary Data and Interim Analysis .....................................................................8 
4.2.1 Blinding .........................................................................................................8 
4.2.2 Interim Analysis ............................................................................................9 
5. 
TREATMENT DESCRIPTIONS .......................................................................................9 
6. 
PHARMACOKINETIC ANALYSIS ...............................................................................11 
6.1 
Measurements and Collection Schedule .................................................................11 
6.2 
Bioanalytical Method ..............................................................................................11 
6.2.1 SXC-2023 ....................................................................................................11 
6.2.2 N-acetylcysteine ..........................................................................................12 
6.2.3 p-Toluic Acid ..............................................................................................12 
6.3 
Investigational Product and PK Analyte Information .............................................12 
6.3.1 SXC-2023 ....................................................................................................12 
6.3.2 N-Acetylcysteine .........................................................................................13 
6.3.3 p-Toluic Acid ..............................................................................................13 
6.4 
Pharmacokinetic Concentrations .............................................................................13 
6.5 
NonCompartmental Pharmacokinetic Analysis and Parameter Calculation ...........13 
6.5.1 Plasma and RBC Pharmacokinetic Parameters ...........................................13 
6.5.2 Urine Pharmacokinetic Parameters .............................................................15 
6.6 
Data Summarization and Presentation ....................................................................16 
6.7 
Statistical Analysis of PK Parameters .....................................................................16 
6.7.1 Food Effect Assessment ..............................................................................16 
6.7.2 Dose Proportionality Analysis ....................................................................17 
7. 
SAFETY ...........................................................................................................................18 
7.1 
Subject Discontinuation ..........................................................................................19 
7.2 
Demographics .........................................................................................................19 
7.3 
Adverse Events........................................................................................................19 
7.4 
Clinical Laboratory Tests (Serum Chemistry, Hematology, Urinalysis) ................20 
7.5 
Vital Signs ...............................................................................................................21 
7.6 
Electrocardiogram ...................................................................................................22 


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Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 4 of 105 
7.7 
Concomitant Medications .......................................................................................23 
7.8 
Physical Examination ..............................................................................................23 
8. 
SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS ................23 
9. 
SUMMARY TABLES AND FIGURES ..........................................................................23 
9.1 
In-text Summary Tables and Figures ......................................................................23 
9.2 
Section 14 Summary Tables and Figures ................................................................26 
9.3 
Section 16 Data Listings .........................................................................................38 
10. TABLE AND FIGURE SHELLS .....................................................................................41 
10.1 In-text Summary Tables Shells ...............................................................................42 
10.2 Figures Shells ..........................................................................................................48 
10.3 Section 14 Summary Tables Shells .........................................................................54 
11. LISTING SHELLS ...........................................................................................................80 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 5 of 105 
1. INTRODUCTION 
The following statistical analysis plan (SAP) provides the framework for the 
summarization of the data from this study. The SAP may change due to unforeseen 
circumstances. Any changes made from the planned analysis within protocol, after 
the unblinding, or locking of the database will be documented in the clinical study 
report (CSR). The section referred to as Table Shells within this SAP describes the 
traceability of the tables, figures, and listings (TFLs) back to the data. Note that the 
header for this page will be the one used for the main body of the CSR.  
Any additional exploratory analyses not addressed within this SAP and/or driven by 
the data, or requested by Promentis Pharmaceuticals, will be considered out of scope 
and must be described in the CSR.   
2. OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
Primary: 
To assess the safety and tolerability of SXC-2023 following administration of single 
ascending doses (SAD) to healthy adult subjects. 
Secondary: 
Objective 1: To assess the pharmacokinetics (PK) of SXC-2023 in plasma, red blood 
cells (RBC), 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’s 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. 
2.2 
Endpoints 
Primary:  
The primary endpoints of the study will be the number and severity of treatment-
emergent adverse events (TEAEs) following single doses of SXC-2023 and placebo. 
Secondary: 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 6 of 105 
The secondary endpoints of the study are the PK parameters following SXC-2023 
administration under fasted and fed conditions. The following PK parameters will 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. 
• 
RBC (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. 
• 
RBC (if applicable): AUC0-t, AUC0-inf, Cmax, Tmax, 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. 
3. STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled, SAD and food-effect (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. Attempts will be made to enroll 50% of each sex in each cohort. 
Screening of subjects will occur within 28 days prior to dosing. 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. 
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 crossing over to receive the same dose of 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 7 of 105 
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 and through 72 hours postdose for 
the PK assessment of SXC-2023, NAC, and p-toluic acid, as appropriate.  
Safety will be monitored throughout the study by repeated clinical and laboratory 
evaluations. Discontinued subjects may be replaced at the discretion of the Sponsor. 
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. At 
least one dose level higher than the dose level selected for the FE cohort, may be 
evaluated for safety and tolerability of the dose at least.  
Subjects will be housed on Day -1, at the time indicated by the clinical research unit 
(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. 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 adverse events (AEs) have occurred 
since the last study visit. 
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. 
4. ANALYSIS POPULATIONS 
4.1 
Analysis Populations 
Safety Population 
All subjects who received any dose of the study drug or placebo will be included in 
the safety evaluations.  
Pharmacokinetic Population 
The PK population will include data from all subjects who received at least one dose 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 8 of 105 
of active treatment (SXC-2023) and completed at least one PK blood draw resulting 
in at least one quantifiable plasma concentration. All available data will be included 
in the concentration tables to the extent possible. Data for each subject will be 
included in the concentration summary statistics with the exceptions described as 
follows: 
• Data from subjects who experience emesis at or before 2 times median Tmax 
for SXC-2023 during the PK sampling period time course may be excluded 
from the summary statistics. 
• Data from subjects who significantly violate a protocol inclusion or exclusion 
criteria, deviate significantly from the protocol, or have unavailable or 
incomplete data, which may influence the PK analysis, will be excluded from 
the PK analysis population.  
Any subject or data excluded from the analysis will be identified, along with their 
reason for exclusion, in the CSR. 
Pharmacokinetic Evaluable Population 
The PK evaluable population will include all subjects in the PK population 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). PK evaluable population will be used in the PK parameter summary 
statistics and in statistical comparisons. For the FE cohort subject must have 
sufficient data in both periods (fed and fasted) to be included in the PK evaluable 
population.  
4.2 
Preliminary Data and Interim Analysis 
4.2.1 Blinding 
This is a double-blind, randomized, placebo controlled study. 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 
will 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. 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 9 of 105 
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. 
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. 
4.2.2 Interim Analysis 
Safety: the PI, Medical Monitor, and Sponsor representative will review all available 
blinded safety data 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. The bioanalytical personnel will scramble subject numbers before sending 
to Celerion for analysis. PK analysis will be performed on SXC-2023, NAC, and 
p-toluic acid plasma concentration-time data using Phoenix® WinNonlin® Version 6.3 
or higher. The parameters listed in Section 6.5 will be calculated. The following 
interim tables and figures will be generated using Phoenix® WinNonlin® Version 6.3 
or higher: Concentration tables, PK parameter tables, mean graphs and superimposed 
(spaghetti) plots generated by cohort and analyte. The interim analysis populations 
will be the same as the analysis populations described in Section 4.1. 
5. TREATMENT DESCRIPTIONS 
SXC-2023 will be supplied as 50 and 200 mg capsules. 
Placebo will be provided as matching placebo capsules. 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 10 of 105 
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 
Treatments will be described as follows: 
Treatment 
Short Description (Legends, 
Columns Headers, Report 
Text) 
Long Description (Titles, Footnotes) 
Placebo 
Pooled Placebo  
A single oral dose of Placebo (Cohorts 1-6) 
Treatment A 
50 mg SXC-2023 Fasted 
A single oral dose of 50 mg SXC-2023 
administered under fasted conditions (Cohort 1) 
Treatment B 
100 mg SXC-2023 Fasted 
A single oral dose of 100 mg SXC-2023 
administered under fasted conditions (Cohort 2) 
Treatment C 
200 mg SXC-2023 Fasted 
A single oral dose of 200 mg SXC-2023 
administered under fasted conditions (Cohort 3)  
Treatment D 
400 mg SXC-2023 Fasted 
A single oral dose of 400 mg SXC-2023 
administered under fasted conditions (Cohort 4) 
Treatment E 
800 mg SXC-2023 Fasted 
A single oral dose of 800 mg SXC-2023 
administered under fasted conditions (Cohort 5) 
Treatment F* 
800 mg SXC-2023 Fed 
A single oral dose of 800 mg SXC-2023 
administered under fed conditions (Cohort 5) 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 11 of 105 
Treatment 
Short Description (Legends, 
Columns Headers, Report 
Text) 
Long Description (Titles, Footnotes) 
Treatment G 
1600 mg SXC-2023 Fed 
A single oral dose of 1600 mg SXC-2023 
administered under fed conditions (Cohort 6) 
 
*Programmer’s note: Treatment letters may change depending on which cohort is 
selected for the FE evaluation. The Description for Treatments F and G will also be 
updated accordingly then.  
All doses of study drug/placebo will be administered with approximately 240 mL of 
water. When administered under fed conditions, SXC-2023 or placebo will be 
administered orally following a high-fat breakfast. 
6. PHARMACOKINETIC ANALYSIS 
6.1 
Measurements and Collection Schedule 
For all subjects, blood samples for the determination of plasma SXC-2023, NAC, and 
p-toluic acid will be collected at the following time points: predose and 0.083, 0.167, 
0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose. For doses 
equal or greater than 200 mg, analytes may also be determined in RBC samples 
collected at selected time points, as necessary. 
All concentration data will be included in the calculation of the individual PK 
parameters, in the individual and superimposed concentration-time plots (based on 
actual sample times), and in the mean concentration-time plots (based on nominal 
sample times). However, if there are any significant deviations from nominal sample 
times, some concentration data may be excluded from mean concentration-time plots 
and/or additional concentration-time plots of the mean data may be provided. All 
deviations and excluded data will be provided and discussed in the CSR. 
For all subjects, urine samples for the determination of urine SXC-2023, NAC, and 
p-toluic acid will be collected at the following intervals: predose, and 0-1, 1-2, 2-4, 4-
8, 8-12, 12-24, 24-48, and 48-72 hours postdose. 
6.2 
Bioanalytical Method 
6.2.1 SXC-2023 
Plasma and urine concentrations of SXC-2023 will be determined using high 
performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) 
methods validated with respect to accuracy, precision, linearity, sensitivity, and 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 12 of 105 
specificity at Covance BioAnalytic (Salt Lake City, Utah). The lower limit of 
quantitation (LLOQ) for SXC-2023 in plasma and urine will be 50.0 ng/mL. Method 
development in RBC is ongoing but concentration will be determined using qualified 
methods with a targeted LLOQ of 50.0 ng/mL. This could vary depending on the 
success/limitations of the on-going bioanalytical method development work. 
6.2.2 N-acetylcysteine  
Plasma and urine concentrations of NAC will be determined using HPLC-MS/MS 
methods validated with respect to accuracy, precision, linearity, sensitivity, and 
specificity at Covance BioAnalytic (Salt Lake City, Utah). The LLOQ for NAC in 
plasma and urine will be 100 ng/mL. Method development in RBC is ongoing but 
concentration will be determined using qualified methods with a targeted LLOQ of 
100 ng/mL. This could vary depending on the success/limitations of the on-going 
bioanalytical method development work. 
6.2.3 p-Toluic Acid 
Plasma and urine concentrations of p-toluic acid will be determined using HPLC-
MS/MS methods validated with respect to accuracy, precision, linearity, sensitivity, 
and specificity at Covance BioAnalytic (Salt Lake City, Utah). The LLOQ for p-
toluic acid in plasma and urine will be 50 ng/mL. Method development in RBC is 
ongoing but concentration will be determined using qualified methods with a targeted 
LLOQ of 50 ng/mL. This could vary depending on the success/limitations of the on-
going bioanalytical method development work. 
6.3 
Investigational Product and PK Analyte Information 
6.3.1 SXC-2023 
Plasma, RBC, and urine will be analyzed for SXC-2023 concentrations. The analyte 
can be described with the following structure and a molecular weight (MW) of 
281.33 g/mol (Figure A). SXC-2023 capsules are an oral dosage form available in 
50 mg and 200 mg unit dose strengths. 
 
Figure A: SXC-2023 (free acid MW = 281.33 g/mol) 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 13 of 105 
The nominal dose will be administered in the form of the free acid therefore, MW 
adjustment will not be needed for the calculation of dose-dependent PK parameters 
since SXC-2023 is dosed in the same form it is measured in. 
6.3.2 N-Acetylcysteine 
Plasma, RBC, and urine will be analyzed for NAC concentrations. Dose-dependent 
PK parameters will not be calculated for NAC; therefore, no MW adjustments will be 
necessary for PK calculations. Molecular weights and structures are contained in the 
Investigator’s Brochure (IB). 
6.3.3 p-Toluic Acid 
Plasma, RBC, and urine will be analyzed for p-toluic acid concentrations. Dose-
dependent PK parameters will not be calculated for p-toluic acid; therefore, no MW 
adjustments will be necessary for PK calculations. Molecular weights and structures 
are contained in the IB. 
6.4 
Pharmacokinetic Concentrations 
Plasma, RBC, and urine concentrations of SXC-2023, NAC, and p-toluic acid, as 
determined at the collection times and per the bioanalytical methods described in 
Section 6.1 and Section 6.2, respectively, will be used for the calculation of the 
plasma, RBC, and urine PK parameters. Concentrations reported from subjects who 
received the placebo treatment will be listed in the concentration tables only. 
6.5 
NonCompartmental Pharmacokinetic Analysis and Parameter Calculation 
6.5.1 Plasma and RBC Pharmacokinetic Parameters 
The appropriate noncompartmental PK parameters will be calculated from the plasma 
SXC-2023, NAC, and p-toluic acid concentration-time data as well as from the RBC 
(if applicable) SXC-2023, NAC, and p-toluic acid concentration-time data using 
Phoenix® WinNonlin® Version 6.3 or higher. Actual sample times will be used in the 
calculations of the PK parameters. The calculation of the actual time for all analytes 
will be in respect to the start of dose administration time of SXC-2023. All PK 
parameters included in the protocol are listed in Table 6.1 below, and are defined as 
appropriate for study design. 
Table 6.1. Noncompartmental Pharmacokinetic Parameters to be Calculated 
Parameter 
Definition 
Method of Determination 
AUC0-t 
Area under the concentration-time curve 
from time 0 to the time of the last 
observed/measured non-zero concentration 
Calculated using the Linear 
Trapezoidal with Linear 
Interpolation Method  


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 14 of 105 
Parameter 
Definition 
Method of Determination 
AUC0-inf 
Area under the concentration-time curve 
from time 0 extrapolated to infinity 
AUC0-∞ = AUC0-t + 
(Clast/kel) 
where Clast is the last 
observed/measured plasma or 
RBC concentration  
Cmax 
The maximum observed concentration 
Taken directly from 
bioanalytical data 
Tmax 
The time to reach Cmax 
Taken from clinical database as 
the difference in the time of 
administration and the time of 
the blood draw which is 
associated with the Cmax. 
t1/2 
Apparent first-order terminal elimination 
half-life 
Calculated as 0.693/Kel 
Kel 
Apparent first-order terminal elimination 
rate constant calculated from a semi-log 
plot of the plasma or RBC concentration 
versus time curve 
Calculated by linear least-
squares regression analysis 
using the maximum number of 
points in the terminal log-linear 
phase (e.g., 3 or more non-zero 
plasma concentrations). 
CL/F 
The apparent total plasma or RBC 
clearance after extravascular 
administration (Calculated for SXC-2023 
only) 
Calculated as 
Dose/(AUC0-inf)  
 
Vz/F 
The apparent volume of distribution 
during the terminal elimination phase after 
extravascular administration (Calculated 
for SXC-2023 only) 
Calculated as  
Dose/(AUC0-inf x Kel) 
Pharmacokinetic parameters will not be calculated for subjects with less than 
3 consecutive postdose time points with quantifiable concentrations. Subjects for 
whom there are insufficient data to calculate the PK parameters will be included in 
the concentration tables only and excluded from the statistical analysis.  
Plasma or RBC concentrations below the limit of quantitation (BLQ) prior to the first 
quantifiable concentration will be set to zero (0) and plasma or RBC concentrations 
BLQ after the first quantifiable concentration will be treated as missing.  
The Kel will be determined using linear regressions composed of least 3 data points. 
The Kel will not be assigned if 1) the terminal elimination phase is not apparent, 2) if 
Tmax is one of the 3 last data points, or 3) if the R2 value is less than 0.8. In cases 
where the Kel interval is not assigned, the values of t½, AUC0-inf, CL/F, and Vz/F 
are considered not calculable and will not be reported. Wherever the resulting t½ is 
more than half as long as the sampling interval, the Kel values and associated 
parameters (t½, AUC0-inf, CL/F, and Vz/F) may not be presented as judged 
appropriate and in accordance with Celerion SOPs.  
Subjects who vomit within twice the median Tmax value for SXC-2023 may be 
excluded from the PK Evaluable population.  


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 15 of 105 
6.5.2 Urine Pharmacokinetic Parameters 
The following PK parameters will be calculated from urine SXC-2023, NAC, and 
p-toluic acid data using SAS® Version 9.3 or higher. 
Table 6.2. Noncompartmental Urine Pharmacokinetic Parameters to be 
Calculated 
 
Parameter 
Definition 
Method of Determination 
Conct1-t2 
Drug concentration in the urine 
during the urine collection interval 
from t1 to t2 
Taken directly from 
bioanalytical data 
Volt1-t2 
Sum of volume of urine collected 
over the entire urine collection 
interval from t1-t2  
Taken directly from CRF 
data 
Aet1-t2 
Amount of analyte excreted in the 
urine collection interval from t1 to 
t2 
Calculated as  
(Curt1-t2 x Vurt1-t2) 
CumAe  
(Ae0-72) 
Total amount of analyte excreted in 
the urine over the entire period of 
sample collection, obtained by 
adding the amounts excreted over 
each collection interval 
Calculated as: 
∑
−
=
+
=
1
1
i
1
i
i
i
)
 t
- 
(t
 
Ae
 
 e
n
A
 
where t1 = 0 and tn = t and 
Aei is measured between ti 
and ti+1, i=1,…,nth 
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 
%Dose 
The percent of dose excreted into 
urine during a urine collection 
interval (Calculated for SXC-2023 
only) 
Calculated as:  
[Aet1-t2]/Dose x 100 
Cum%Dose 
(%Fe) 
The percent of dose excreted into 
urine over the entire period of 
sample collection (Calculated for 
SXC-2023 only) 
Calculated as:  
[CumAe]/Dose x 100 
For the calculation of descriptive statistics and urine PK parameters, urine 
concentrations that are BLQ will be set to zero. Cumulative urine PK parameters 
(e.g., CumAe) and derived parameters (e.g., %Dose and Cum%Dose) after a missing 
sample (e.g., lost part of void, volume not recorded, etc.) will continue to be 
presented, but will be excluded from the summary statistics. 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 16 of 105 
6.6 
Data Summarization and Presentation 
All SXC-2023, NAC, and p-toluic acid PK concentrations and/or PK parameters 
descriptive statistics will be generated using SAS®. 
The plasma, RBC, and urine concentrations of SXC-2023, NAC, and p-toluic acid will 
be listed and summarized by analyte, treatment (dose level) and time point or collection 
interval for all subjects in the PK Population. Plasma, RBC, and urine concentrations 
of SXC-2023, NAC, and p-toluic acid will be presented with the same level of precision 
as received from the bioanalytical laboratory. Summary statistics, including sample 
size (n), arithmetic mean (Mean), standard deviation (SD), coefficient of variation 
(CV%), standard error of the mean (SEM), minimum, median, and maximum will be 
calculated for all nominal concentration time points. Excluded subjects will be included 
in the concentration listings, but will be excluded from the summary statistics and noted 
as such in the tables. All BLQ values will be presented as “BLQ” in the concentration 
listings and footnoted accordingly.  
Mean and individual concentration-time profiles will be presented on linear and semi-
log scales. Linear mean plots will be presented with and without SD. Superimposed 
profiles (spaghetti plots) will be presented per treatment on linear scale. 
Plasma, RBC (if applicable), and urine PK parameters for SXC-2023, NAC, and p-
toluic acid will be listed and summarized by analyte and treatment (dose level) for all 
subjects in the PK Evaluable Population. Cmax will be presented with the precision 
of the bio data. AUCs will be reported to 3-4 significant figures (to be determined by 
the PKist once bio data are received). Tmax and t1/2 will be presented with 2 decimal 
places. Kel, Vz/F, and CL/F will be presented with 3 significant figures. Summary 
statistics (n, arithmetic mean, SD, CV%, SEM, minimum, median, maximum, 
geometric mean [Geom Mean] and geometric CV% [Geom CV%]) will be calculated 
for plasma, RBC, and urine SXC-2023, NAC, and p-toluic acid PK parameters. 
Excluded subjects will be listed in the PK parameter tables, but will be excluded from 
the summary statistics and noted as such in the tables. 
The level of precision for each concentration and PK parameter statistic will be 
presented as follows: minimum/maximum in same precision as in bioanalytical data 
and/or parameter output, mean/median/Geom.Mean in one more level of precision 
than minimum/maximum, SD/SEM in one more level of precision than mean/median, 
n will be presented as an integer and CV% and Geom CV will be presented to the 
nearest tenth. 
6.7 
Statistical Analysis of PK Parameters 
6.7.1 Food Effect Assessment 
A comparison will be performed on the natural-log (ln)-transformed SXC-2023 
plasma and RBC (if applicable) PK parameters Cmax, AUC0-t, and AUC0-inf to 


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 17 of 105 
evaluate the relative bioavailability of fed versus fasted conditions, by performing an 
analysis of variance (ANOVA) model using PROC MIXED of SAS®. The ANOVA 
model will include treatment (fed or fasted) as a fixed effect and subject as a random 
effect. The inferential results (least-squares means [LSMs], difference between LS 
means, and 90% CIs of the difference) will be exponentiated to the original scale. 
Geometric LSM, geometric mean ratios (GMRs) and 90% CIs will be presented. The 
ratios and 90% CIs will be expressed as a percentage relative to the fasting 
conditions. 
The ANOVA will be performed using the following SAS® code: 
PROC MIXED; 
CLASS TREATMENT SUBJECT; 
MODEL PK_PARAMETER = TREATMENT; 
RANDOM SUBJECT; 
*ESTIMATE “FED vs. FASTED” TREATMENT -1 1/ cl alpha=0.1 e; 
* Programmer Note: Please only include data from the food effect cohort in this 
model. Prior to running the model, please contact biostatistician to confirm 
coefficients for the ESTIMATE statement.  
6.7.2 Dose Proportionality Analysis 
Dose proportionality will be evaluated for SXC-2023, NAC, and p-toluic AUC0-t, 
AUC0-inf, and Cmax plasma PK 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. 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 18 of 105 
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 Step 1 (see below), 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).  
The following SAS® PROC MIXED code will be used: 
Step 1: Test of a quadratic and cubic effects: 
PROC MIXED; 
MODEL LN_PKPARAMETER = LNDOSE  LNDOSE2 LNDOSE3   /DDFM=KR 
HTYPE = 1 SOLUTION; 
RUN; 
 
Where LNDOSE = Ln(Dose) and LNDOSEN = [Ln(dose)-Mean(Ln(dose))]N. The 
centralized quadratic and cubic terms are used to avoid multicollinearity and 
estimation problems. 
If the statistical linear relationship is established in step 1, a second step (see below) 
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 the following SAS® PROC MIXED code: 
Step 2: Test for a linear effect and obtaining a 95% CI for the slope parameter: 
PROC MIXED; 
MODEL LPARM = LNDOSE / DDFM = KR SOLUTION CL ALPHA=0.05; 
RUN; 
 
Where LNDOSE = Ln(Dose) 
7. SAFETY  
All case report form (CRF) data will be listed by subject and chronologically by 
assessment time points. This will include rechecks, unscheduled assessments, and 
early termination.  
Applicable continuous variables will be summarized using n, arithmetic mean, SD, 
minimum, median, and maximum. Data from subjects who received the placebo 


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 19 of 105 
treatment (fasted or fed) will be pooled across cohorts. Therefore, for subjects in the 
food effect cohort, the placebo treatment received in Periods 1 and 2 will be 
summarized under the same treatment.  
The level of precision will be presented as follows: minimum/maximum in the same 
precision as in the database, mean/median in one more precision level than 
minimum/maximum, SD in one more precision level than mean/median, and n will be 
presented as an integer. 
Where individual data points are missing because of dropouts or other reasons, the 
data will be summarized based on reduced denominators. 
No inferential statistics will be performed for safety assessments. 
7.1 
Subject Discontinuation 
Subjects will be summarized by number of subjects enrolled, completed, and 
discontinued the study with discontinuation reasons by randomized treatment 
(including pooled placebo) and overall. Subjects enrolled in the food effect cohort 
will be summarized according to the treatment they were randomized to receive in 
Period 1.   
7.2 
Demographics 
Descriptive statistics will be calculated for continuous variables (age, weight, height, 
and body mass index [BMI]) by randomized treatment (including pooled placebo) 
and overall. Weight, height, and BMI will be summarized at screening. Age will be 
derived from date of birth to date of first dosing (Day 1 of Period 1). Frequency 
counts will be provided for categorical variables (race, ethnicity, and sex) by 
randomized treatment (including pooled placebo) and overall. Subjects enrolled in the 
food effect cohort will be summarized according to the treatment they were 
randomized to receive in Period 1. 
7.3 
Adverse Events 
All AEs occurring during this clinical trial will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA®), Version 20.0.  
All AEs captured in the database will be listed in by-subject data listings including 
verbatim term, coded term, treatment, severity, relationship to study medication, and 
actions; however, only TEAEs will be summarized. 
A TEAE is defined as an AE that is starting or worsening at the time of or after study 
drug administration. Each TEAE will be attributed to a treatment based on the onset 
date and time of the AE. For subjects enrolled in the food effect cohort, an AE that 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 20 of 105 
occurs during the washout period between drugs will be considered treatment-
emergent to the treatment administered in Period 1.  
If an AE increases in severity, that AE will be given a resolution date and time and a 
new record will be initiated with the new severity. If the severity of an AE remains 
the same or decreases, the AE will be kept open through to resolution.  
If the onset date and/or time of an AE is/are missing, the AE will be treated as TEAE 
to the randomized treatment, unless the onset date of the AE is known to have 
occurred prior to dosing. For subjects enrolled in the food effect cohort, if the onset 
time of an AE is missing and the onset date is the same as the treatment dosing date, 
then the AE will be considered treatment emergent to both treatments. If onset time of 
an AE is missing and the onset date does not fall on a dosing date, then the AE will be 
considered treatment emergent for the last treatment administered. If the onset date of 
an AE is missing, then the AE will be considered treatment emergent and attributed to 
both treatments, unless the onset date is known to have occurred within or between 
specific treatment periods. 
TEAEs will be tabulated by System Organ Class (SOC) and Preferred Term. 
Summary tables will include number of subjects reporting the AE and as percent of 
number of subjects dosed by treatment (including pooled placebo), and overall. The 
number of AEs will be tabulated in a similar manner. Tables which tabulate the 
number of TEAEs by severity and relationship to study treatment will also be 
included.  
Serious adverse events (SAEs), if present, will also be listed. Applicable narratives 
will be included in the CSR.  
7.4 
Clinical Laboratory Tests (Serum Chemistry, Hematology, Urinalysis) 
All clinical laboratory test results will be presented in by-subject data listings; 
however, only serum chemistry (including Total testosterone, LH, and FSH), 
hematology, and urinalysis values will be summarized.   
Serum chemistry (including Total testosterone, LH, and FSH), hematology, and 
urinalysis tests will be performed at the following time points: 
Table 7-1 Clinical Laboratory Collection Time Points 
Test* 
Period 
Day 
Time Point 
Serum Chemistry, 
Hematology, 
Urinalysis  
Screen 
 
 
1,2** 
 
-1 
Check-in 
2 
Hour 24 
4 / ET 
Hour 72 or Early Termination 
*Coagulation, HIV/Hepatitis and urine cotinine tests will also be performed at Screening. 
Serum pregnancy tests will be performed at Screening, Day -1 and Day 4 of each period. 
Urine cotinine screen will be performed at Screening and Urine alcohol and drug screens 
will be performed at Screening and Day -1 of each period.  


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
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** Period 2 assessments will only be performed for subjects included in the food effect 
cohort.  
 
 
 
Out-of-normal-range flags will be recorded as follows: high (H) and low (L) for 
numerical results and did-not-match (*) for categorical results. If a value fails the 
reference range, it will automatically be compared to a computer clinically significant 
(CS) range. If the value falls within the computer CS range, it will be noted as “N” 
for not clinically significant. If the value fails the computer CS range (i.e., falls 
outside of the CS range), it will be flagged with a “Y”, which prompts the PI to 
determine how the out-of-range value should be followed using 4 Investigator flags: 
"N", not clinically significant; "R", requesting a recheck; "^", checking at the next 
scheduled visit; or "Y", clinically significant. To distinguish the PI flag from the 
computer CS range flags, the PI flags of “N” and “Y” will be presented as “-” and 
“+”, respectively, in the data listing. Additionally, a derived flag based on a search of 
the PI comments for a comment of “CS” or “Clinically Significant” will be used. The 
derived flag will be populated with “+” if the positive clinically significant 
determination is found in the comments for cases when the PI flag is populated with a 
“^” or an “R”. 
Out-of-range values and corresponding recheck results will be listed. Results that are 
indicated as CS by the PI (either in the PI flag or in PI comments) will be listed in the 
table. 
For all numeric laboratory values, descriptive statistics will be presented for each 
laboratory test by assessment time point and treatment. Change from baseline will be 
summarized in a similar manner. Baseline is defined as the result closest and prior to 
dose which may include unscheduled or recheck results. This will typically be the 
result collected on Day -1 in each period. Postdose unscheduled events or rechecks 
will not be included in summaries. Similarly, early termination results will not be 
included in summaries. 
For each laboratory test, a shift table will be developed to compare the frequency of 
the results at baseline (above reference, within reference, or below reference) with the 
respective postdose results. For urinalysis tests, the categories are normal and outside 
normal. 
7.5 
Vital Signs 
Single measurements of oral body temperature, respiratory rate, blood pressure and 
heart rate will be performed with subjects in a seated position at the following time 
points:   
 


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 22 of 105 
Table 7-2 Vital Signs Collection Time Points 
Vital Sign 
Measurement 
Period 
Day 
Time Point 
Blood Pressure 
(Systolic, 
Diastolic), Heart 
Rate, Body 
Temperature, 
Respiratory Rate 
Screen 
 
 
1, 2** 
-1  
Predose 
1 
Hour 2, Hour 4 
2 
Hour 24 
3 
Hour 48 
4 / ET 
Hour 72 or Early Termination 
FU* 
Follow-Up 
*The follow-up measurements will be collected approximately 7 days after the last study 
drug/placebo administration.  
** Period 2 assessments will only be performed for subjects included in the food effect 
cohort.  
 
All vital signs data will be listed by subject. Descriptive statistics will be reported for 
all vital signs measurements by treatment and time point. Change from baseline will 
be summarized in a similar way. Baseline is defined as the result closest and prior to 
first dosing in each period, which may include unscheduled or recheck results. This 
will typically be the predose measurement collected within 24 hours prior to dosing in 
each period. For subjects in the food effect cohort, baseline for the follow-up time 
point will be the predose measurement collected in Period 2. Postdose unscheduled 
events, rechecks, or early termination records will not be included in summaries. 
7.6 
Electrocardiogram  
Single 12-lead ECG parameters (i.e., HR, PR, QRS, QT, and QTcF [QT corrected for 
heart rate using Fridericia’s equation]) will be collected with subjects in supine 
position at the following time points:   
Table 7-3 12-lead ECG Collection Time Points 
ECG Parameter 
Period 
Day 
Time Point 
HR, PR, QRS, QT, 
QTcF  
Screen 
 
 
1, 2* 
-1  
Predose 
1 
Hour 2 
2 
Hour 24 
4 / ET 
Hour 72 or Early Termination 
*Period 2 assessments will only be performed for subjects included in the food effect 
cohort.  
 
 
Descriptive statistics will be reported for ECG parameters by treatment and time 
point. Change from baseline will be summarized in a similar way. Baseline is defined 
as the result closest and prior to dosing, which may include unscheduled or recheck 
results. This will typically be the predose measurement collected within 24 hours 
prior to dosing in each period. Postdose unscheduled events or rechecks will not be 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 23 of 105 
included in summaries. Similarly, early termination results will not be included in 
summaries. QTcF values greater than 450 and QTcF changes from baseline greater 
than 30 msec will be flagged in the data listing.   
A normal-abnormal shift from baseline table will be presented for the ECG overall 
interpretation by treatment and time point.   
7.7 
Concomitant Medications 
All concomitant medications recorded during the study will be coded with the WHO 
Dictionary Version 01MAR2017 and listed. 
7.8 
Physical Examination 
A full physical examination will be performed at Screening. Symptom-driven 
physical examinations may be performed at other times, if deemed necessary by the 
PI or designee. Abnormal findings will be reported as medical history or adverse 
events. All data found in the CRF will be listed.  
8. SUMMARY OF CHANGES FROM PROTOCOL-PLANNED ANALYSIS 
The analyses described in this SAP are aligned with those analyses described in the 
protocol.  
9. SUMMARY TABLES AND FIGURES 
Summary tables and figures are numbered following the International Conference on 
Harmonization (ICH) structure but may be renumbered as appropriate during the 
compilation of the tables and figures for the CSR. Note that all PK and safety 
summary tables and figures will be generated using SAS® Version 9.3 or higher. 
9.1 
In-text Summary Tables and Figures 
The following is a list of table and figure titles that will be included in the text of the 
CSR. Tables and figures will be numbered appropriately during compilation of the 
CSR. 
Section 10: 
Table 10-1 
Summary of Disposition  
Section 11: 
Table 11-1 
Demographic Summary  
SXC-2023 In-Text Tables and Figures 


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Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 24 of 105 
Table 11-2 
Summary of Plasma SXC-2023 Pharmacokinetics Following Single 
Oral Doses of SXC-2023 Administered Under Fasted or Fed 
Conditions  
Table 11-3 
Summary of Statistical Comparisons of Plasma SXC-2023 
Pharmacokinetic Parameters Following Single Oral Doses of SXC-
2023 Administered Under Fed Versus Fasted Conditions  
Table 11-4 
Dose Proportionality Analysis of Plasma SXC-2023 Pharmacokinetic 
Parameters Following Single Oral Doses of SXC-2023 Administered 
Under Fasted Conditions  
Table 11-5 
Summary of RBC SXC-2023 Pharmacokinetics Following Single Oral 
Doses of SXC-2023 Administered Under Fasted or Fed Conditions  
Table 11-6 
Summary of Statistical Comparisons of RBC SXC-2023 
Pharmacokinetic Parameters Following Single Oral Doses of SXC-
2023 Administered Under Fed Versus Fasted Conditions  
Table 11-7 
Summary of Urine SXC-2023 Pharmacokinetics Following Single 
Oral Doses of SXC-2023 Administered Under Fasted or Fed 
Conditions  
Figure 11-1 
Arithmetic Mean Plasma SXC-2023 Concentration-Time Profiles 
Following Administration of Single Oral Doses of SXC-2023 Under 
Fasted or Fed Conditions 
Figure 11-2 
Arithmetic Mean Urine SXC-2023 Amount Excreted-Time Profiles 
Following Administration of Single Oral Doses of SXC-2023 Under 
Fasted or Fed Conditions 
Figure 11-3 
Arithmetic Mean Percent of SXC-2023 Dose Excreted in Urine-Time 
Profiles Following Administration of Single Oral Doses of SXC-2023 
Under Fasted or Fed Conditions 
NAC In-Text Tables and Figures 
Table 11-8 
Summary of Plasma NAC Pharmacokinetics Following Single Oral 
Doses of SXC-2023 Administered Under Fasted or Fed Conditions  
Table 11-9 
Dose Proportionality Analysis of Plasma NAC Pharmacokinetic 
Parameters Following Single Oral Doses of SXC-2023 Administered 
Under Fasted Conditions  
Table 11-10 
Summary of RBC NAC Pharmacokinetics Following Single Oral 
Doses of SXC-2023 Administered Under Fasted or Fed Conditions  


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 25 of 105 
Table 11-11 
Summary of Urine NAC Pharmacokinetics Following Single Oral 
Doses of SXC-2023 Administered Under Fasted or Fed Conditions  
Figure 11-4 
Arithmetic Mean Plasma NAC Concentration-Time Profiles Following 
Administration of Single Oral Doses of SXC-2023 Under Fasted or 
Fed Conditions  
Figure 11-5 
Arithmetic Mean Urine NAC Amount Excreted-Time Profiles 
Following Administration of Single Oral Doses of SXC-2023 Under 
Fasted or Fed Conditions 
p-Toluic Acid In-Text Tables and Figures 
Table 11-12 
Summary of Plasma p-Toluic Acid Pharmacokinetics Following 
Single Oral Doses of SXC-2023 Administered Under Fasted or Fed 
Conditions  
Table 11-13 
Dose Proportionality Analysis of Plasma p-Toluic Acid 
Pharmacokinetic Parameters Following Single Oral Doses of SXC-
2023 Administered Under Fasted Conditions  
Table 11-14 
Summary of RBC p-Toluic Acid Pharmacokinetics Following Single 
Oral Doses of SXC-2023 Administered Under Fasted or Fed 
Conditions  
Table 11-15 
Summary of Urine p-Toluic Acid Pharmacokinetics Following Single 
Oral Doses of SXC-2023 Administered Under Fasted or Fed 
Conditions  
Figure 11-6 
Arithmetic Mean Plasma p-Toluic Acid Concentration-Time Profiles 
Following Administration of Single Oral Doses of SXC-2023 Under 
Fasted or Fed Conditions  
Figure 11-7 
Arithmetic Mean Urine p-Toluic Acid Amount Excreted-Time Profiles 
Following Administration of Single Oral Doses of SXC-2023 Under 
Fasted or Fed Conditions 
Programmer’s note if no parameters can be determined in RBC Tables 11-5, 11-6, 
11-10, and 11-14, as appropriate, will not be generated and table 
numbers will be updated accordingly. 
Section 12: 
Table 12-1 
Treatment-Emergent Adverse Event Frequency by Treatment - 
Number of Subjects Reporting the Event (% of Subjects Dosed) 


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Statistical Analysis Plan                                     28 February 2018                                                  Page 26 of 105 
9.2 
Section 14 Summary Tables and Figures 
The following is a list of table and figure titles that will be included in Section 14 of 
the report. Table and figure titles may be renumbered as appropriate during the 
compilation of the report.  
14.1 
Demographic Data Summary Tables  
Table 14.1.1 Summary of Disposition (Safety Population) 
Table 14.1.2 Demographic Summary (Safety Population) 
14.2 
Pharmacokinetic Data Summary Tables and Figures  
14.2.1 SXC-2023 Tables and Figures 
14.2.1.1 Plasma SXC-2023 Tables 
Table 14.2.1.1.1 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 50 mg SXC-2023 Administered Under 
Fasted Conditions (Cohort 1 - Treatment A) 
(Pharmacokinetic Population) 
Table 14.2.1.1.2 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 100 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 2 - Treatment B) 
(Pharmacokinetic Population) 
Table 14.2.1.1.3 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Population) 
Table 14.2.1.1.4 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 400 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 4 - Treatment D) 
(Pharmacokinetic Population) 
Table 14.2.1.1.5 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 5 - Treatment E) 
(Pharmacokinetic Population) 
Table 14.2.1.1.6 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fed Conditions (Cohort 5 - Treatment F) 
(Pharmacokinetic Population) 
Table 14.2.1.1.7 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 1600 mg SXC-2023 Administered 


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Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 27 of 105 
Under Fasted Conditions (Cohort 6 - Treatment G) 
(Pharmacokinetic Population) 
Table 14.2.1.1.8 Plasma SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of Placebo Administered under Fasted 
Conditions (Cohorts 1-6 – Pooled Placebo)  
Table 14.2.1.1.9 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 50 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 1 - Treatment A) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.10 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 100 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 2 - Treatment B) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.11 Plasma SXC-2023 Pharmacokinetic Parameters Following  
a Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.12 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 400 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 4 - Treatment D) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.13 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 5 - Treatment E) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.14 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fed Conditions (Cohort 5 - Treatment F) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.15 Plasma SXC-2023 Pharmacokinetic Parameters Following 
a Single Oral Dose of 1600 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 6 - Treatment G) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.16 Intervals (Hours) Used for Determination Plasma 
SXC-2023 Kel Values (Pharmacokinetic Population) 
Table 14.2.1.1.17 Statistical Comparisons of Plasma SXC-2023 
Pharmacokinetic Parameters: Fed Versus Fasted Conditions 
(Cohort 5 - Pharmacokinetic Evaluable Population) 
Table 14.2.1.1.18 Dose Proportionality Analysis of Plasma SXC-2023 
Pharmacokinetic Parameters Under Fasted Conditions 
(Pharmacokinetic Evaluable Population) 


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Statistical Analysis Plan                                     28 February 2018                                                  Page 28 of 105 
14.2.1.2 
Plasma SXC-2023 Figures 
Figure 14.2.1.2.1 Mean (SD) Plasma SXC-2023 Concentration Versus Time 
Profiles Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G - 
Pharmacokinetic Evaluable Population) 
Figure 14.2.1.2.2 Mean Plasma SXC-2023 Concentration Versus Time 
Profiles Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G - 
Pharmacokinetic Evaluable Population) 
Figure 14.2.1.2.3 Mean Plasma SXC-2023 Concentration Versus Time 
Profiles Following Administration of Single Oral Doses of 
SXC-2023 (Semi-Log Scale) (Treatments A-G 
Pharmacokinetic Evaluable Population) 
Figure 14.2.1.2.4 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 50 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment A)  (Linear Scale)  
Figure 14.2.1.2.5 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 100 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment B)  (Linear Scale)  
Figure 14.2.1.2.6 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 200 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment C)  (Linear Scale)  
Figure 14.2.1.2.7 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 400 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment D)  (Linear Scale)  
Figure 14.2.1.2.8 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 800 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment E)  (Linear Scale)  
Figure 14.2.1.2.9 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 800 mg SXC-2023 Administered Under Fed Conditions 
(Treatment F)  (Linear Scale)  
Figure 14.2.1.2.10 Superimposed Plasma SXC-2023 Concentration Versus 
Time Profiles Following Administration a Single Oral Dose 
of 1600 mg SXC-2023 Administered Under Fasted 
Conditions (Treatment G)  (Linear Scale)  
 


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 29 of 105 
Programmer’s note: Figures 14.2.1.2.4 through 14.2.1.2.10 will be spaghetti 
plots. 
 
14.2.1.3 RBC SXC-2023 Tables 
Table 14.2.1.3.1 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Population) 
Table 14.2.1.3.2 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 400 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 4 - Treatment D) 
(Pharmacokinetic Population) 
Table 14.2.1.3.3 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 5 - Treatment E) 
(Pharmacokinetic Population) 
Table 14.2.1.3.4 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fed Conditions (Cohort 5 - Treatment F) 
(Pharmacokinetic Population) 
Table 14.2.1.3.5 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of 1600 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 6 - Treatment G) 
(Pharmacokinetic Population) 
Table 14.2.1.3.6 RBC SXC-2023 Concentrations (<units>) Following a 
Single Oral Dose of Placebo Administered under Fasted 
Conditions (Cohorts 1-6 – Pooled Placebo)  
Table 14.2.1.3.7 RBC SXC-2023 Pharmacokinetic Parameters Following a 
Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.3.8 RBC SXC-2023 Pharmacokinetic Parameters Following a 
Single Oral Dose of 400 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 4 - Treatment D) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.3.9 RBC SXC-2023 Pharmacokinetic Parameters Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 5 - Treatment E) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.3.10 RBC SXC-2023 Pharmacokinetic Parameters Following a 
Single Oral Dose of 800 mg SXC-2023 Administered 


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SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 30 of 105 
Under Fed Conditions (Cohort 5 - Treatment F) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.3.11 RBC SXC-2023 Pharmacokinetic Parameters Following a 
Single Oral Dose of 1600 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 6 - Treatment G) 
(Pharmacokinetic Evaluable Population) 
Table 14.2.1.3.12 Intervals (Hours) Used for Determination RBC SXC-2023 
Kel Values (Pharmacokinetic Population) 
Table 14.2.1.3.13 Statistical Comparisons of RBC SXC-2023 
Pharmacokinetic Parameters: Fed Versus Fasted Conditions 
(Cohort 5 - Pharmacokinetic Evaluable Population) 
Programmer’s note: if RBC PK parameters cannot be determined tables 
14.2.1.3.7 through 14.2.1.3.13 will not be generated. 
14.2.1.4 
RBC SXC-2023 Figures 
Figure 14.2.1.4.1 Mean (SD) RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments C-G - 
Pharmacokinetic Evaluable Population) 
Figure 14.2.1.4.2 Mean RBC SXC-2023 Concentration Versus Time Profiles 
Following Administration of Single Oral Doses of SXC-
2023 (Linear Scale) (Treatments C-G - Pharmacokinetic 
Evaluable Population) 
Figure 14.2.1.4.3 Mean RBC SXC-2023 Concentration Versus Time Profiles 
Following Administration of Single Oral Doses of SXC-
2023 (Semi-Log Scale) (Treatments C-G - Pharmacokinetic 
Evaluable Population) 
Figure 14.2.1.4.4 Superimposed RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration a Single Oral Dose of 
200 mg SXC-2023 Administered Under Fasted Conditions 
(Treatment C)  (Linear Scale)  
Figure 14.2.1.4.5 Superimposed RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration a Single Oral Dose of 
400 mg SXC-2023 Administered Under Fasted Conditions 
(Treatment D)  (Linear Scale)  
Figure 14.2.1.4.6 Superimposed RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration a Single Oral Dose of 
800 mg SXC-2023 Administered Under Fasted Conditions 
(Treatment E)  (Linear Scale)  
Figure 14.2.1.4.7 Superimposed RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration a Single Oral Dose of 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 31 of 105 
800 mg SXC-2023 Administered Under Fed Conditions 
(Treatment F)  (Linear Scale)  
Figure 14.2.1.4.8 Superimposed RBC SXC-2023 Concentration Versus Time 
Profiles Following Administration a Single Oral Dose of 
1600 mg SXC-2023 Administered Under Fasted Conditions 
(Treatment G)  (Linear Scale)  
 
Programmer’s note: Figures 14.2.1.4.4 through 14.2.1.4.8 will be spaghetti 
plots. 
 
14.2.1.5 
Urine SXC-2023 Tables 
Table 14.2.1.5.1 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 50 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 1 - Treatment A) (Pharmacokinetic 
Population) 
Table 14.2.1.5.2 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 100 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 2 - Treatment B) (Pharmacokinetic 
Population) 
Table 14.2.1.5.3 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 200 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 3 - Treatment C) (Pharmacokinetic 
Population) 
Table 14.2.1.5.4 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 400 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 4 - Treatment D) (Pharmacokinetic 
Population) 
Table 14.2.1.5.5 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 800 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 5 - Treatment E) (Pharmacokinetic 
Population) 
Table 14.2.1.5.6 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 800 mg SXC-2023 Administered Under Fed 
Conditions (Cohort 5 - Treatment F) (Pharmacokinetic 
Population) 
Table 14.2.1.5.7 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of 1600 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 6 - Treatment G) (Pharmacokinetic 
Population) 
Table 14.2.1.5.8 Urinary Excretion of SXC-2023 Following a Single Oral 
Dose of Placebo Administered Under Fasted Conditions 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 32 of 105 
(Cohorts 1-6 – Pooled Placebo) (Pharmacokinetic 
Population) 
 
14.2.1.6 
Urine SXC-2023 Figures 
Figure 14.2.1.6.1 Mean (SD) Cumulative Urine SXC-2023 Amounts 
Excreted Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
Figure 14.2.1.6.2 Mean Cumulative Urine SXC-2023 Amounts Excreted 
Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
Figure 14.2.1.6.3 Mean (SD) Cumulative Percent of SXC-2023 Dose 
Excreted in Urine Following Administration of Single Oral 
Doses of SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
Figure 14.2.1.6.4 Mean Cumulative Percent of SXC-2023 Dose Excreted in 
Urine Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
 
Programmer’s note: Figures 14.2.1.6.1 through 14.2.1.6.4 will present 
cumulative amount (CumAe)/fraction excreted (Cum%Dose) 
versus the nominal end of the collection interval (0, 1, 2, 4, 8, 
12, 24, 48, and 72 hours postdose). 
 
14.2.2 N-acetylcysteine Tables and Figures 
14.2.2.1 Plasma N-acetylcysteine Tables 
Table 14.2.2.1.1 Plasma N-acetylcysteine Concentrations (<units>) 
Following a Single Oral Dose of 50 mg SXC-2023 
Administered Under Fasted Conditions (Cohort 1 - 
Treatment A) (Pharmacokinetic Population) 
Programmer’s note: Tables 14.2.2.1.1 through 14.2.2.1.17 will present 
plasma NAC data and will follow the same format as 
Tables 14.2.1.1.1 through 14.2.1.1.18 (with the exception 
that the statistical comparisons for FE, corresponding to 
SXC-2023 Table 14.2.1.1.17, will not be presented). 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 33 of 105 
14.2.2.2 
Plasma N-acetylcysteine Figures 
Figure 14.2.2.2.1 Mean (SD) Plasma N-acetylcysteine Concentration Versus 
Time Profiles Following Administration of Single Oral 
Doses of SXC-2023 (Linear Scale) (Treatments A-G - 
Pharmacokinetic Evaluable Population) 
Programmer’s note: Figures 14.2.2.2.1 through 14.2.2.2.10 will present 
plasma NAC data and will follow the same format as 
Figures 14.2.1.2.1 through 14.2.1.2.10. 
Programmer’s note: Figures 14.2.2.2.4 through 14.2.2.2.10 will be spaghetti 
plots. 
14.2.2.3 RBC N-acetylcysteine Tables 
Table 14.2.2.3.1 RBC N-acetylcysteine Concentrations (<units>) Following 
a Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Population) 
Programmer’s note: Tables 14.2.2.3.1 through 14.2.2.3.12 will present RBC 
NAC data and will follow the same format as Tables 
14.2.1.3.1 through 14.2.1.3.12 
Programmer’s note: if RBC PK parameters cannot be determined tables 
14.2.2.3.7 through 14.2.2.3.12 will not be generated. 
14.2.2.4 
RBC N-acetylcysteine Figures 
Figure 14.2.2.4.1 Mean (SD) RBC N-acetylcysteine Concentration Versus 
Time Profiles Following Administration of Single Oral 
Doses of SXC-2023 (Linear Scale) (Treatments C-G - 
Pharmacokinetic Evaluable Population) 
Programmer’s note: Figures 14.2.2.4.1 through 14.2.2.4.8 will present RBC 
NAC data and will follow the same format as Figures 
14.2.1.4.1 through 14.2.1.4.8. 
Programmer’s note: Figures 14.2.2.4.4 through 14.2.2.4.8 will be spaghetti 
plots. 
14.2.2.5 
Urine N-acetylcysteine Tables 
Table 14.2.2.5.1 Urinary Excretion of N-acetylcysteine Following a Single 
Oral Dose of 50 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 1 - Treatment A) (Pharmacokinetic 
Population) 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 34 of 105 
Programmer’s note: Tables 14.2.2.5.1 through 14.2.2.5.8 will present urine 
NAC data and will follow the same format as Tables 
14.2.1.5.1 through 14.2.1.5.8. 
14.2.2.6 
Urine N-acetylcysteine Figures 
Figure 14.2.2.6.1 Mean (SD) Cumulative Urine N-acetylcysteine Amounts 
Excreted Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
Figure 14.2.2.6.2 Mean Cumulative Urine N-acetylcysteine Amounts 
Excreted Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
 
Programmer’s note: Figures 14.2.2.6.1 and 14.2.2.6.2 will present urine NAC 
data and will follow the same format as Figures 14.2.1.6.1 
and 14.2.1.6.2. 
Programmer’s note: Figures 14.2.1.6.1 and 14.2.1.6.2 will present cumulative 
amounts excreted (CumAe) versus the nominal end of the 
collection interval (0, 1, 2, 4, 8, 12, 24, 48, and 72 hours 
postdose). 
14.2.3 p-Toluic Acid Tables and Figures 
14.2.3.1 Plasma p-Toluic Acid Tables 
Table 14.2.3.1.1 Plasma p-Toluic Acid Concentrations (<units>) Following 
a Single Oral Dose of 50 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 1 - Treatment A) 
(Pharmacokinetic Population) 
Programmer’s note: Tables 14.2.3.1.1 through 14.2.3.1.17 will present 
plasma p-toluic acid data and will follow the same format 
as Tables 14.2.1.1.1 through 14.2.1.1.18 (with the 
exception that the statistical comparison for FE, 
corresponding to SXC-2023 Table 14.2.1.1.17, will not be 
presented. 
14.2.3.2 
Plasma p-Toluic Acid Figures 
Figure 14.2.3.2.1 Mean (SD) Plasma p-Toluic Acid Concentration Versus 
Time Profiles Following Administration of Single Oral 
Doses of SXC-2023 (Linear Scale) (Treatments A-G - 
Pharmacokinetic Evaluable Population) 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 35 of 105 
Programmer’s note: Figures 14.2.3.2.1 through 14.2.3.2.10 will present 
plasma p-Toluic Acid data and will follow the same format 
as Figures 14.2.1.2.1 through 14.2.1.2.10. 
Programmer’s note: Figures 14.2.3.2.4 through 14.2.3.2.10 will be spaghetti 
plots. 
14.2.3.3 RBC p-Toluic Acid Tables 
Table 14.2.3.3.1 RBC p-Toluic Acid Concentrations (<units>) Following a 
Single Oral Dose of 200 mg SXC-2023 Administered 
Under Fasted Conditions (Cohort 3 - Treatment C) 
(Pharmacokinetic Population) 
Programmer’s note: Tables 14.2.3.3.1 through 14.2.3.3.12 will present RBC 
p-toluic acid data and will follow the same format as 
Tables 14.2.1.3.1 through 14.2.1.3.12  
Programmer’s note: if RBC PK parameters cannot be determined tables 
14.2.3.3.7 through 14.2.3.3.12 will not be generated. 
14.2.3.4 
RBC p-Toluic Acid Figures 
Figure 14.2.3.4.1 Mean (SD) RBC p-Toluic Acid Concentration Versus Time 
Profiles Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments C-G - 
Pharmacokinetic Evaluable Population) 
Programmer’s note: Figures 14.2.3.4.1 through 14.2.3.4.8 will present RBC 
p-toluic acid data and will follow the same format as 
Figures 14.2.1.4.1 through 14.2.1.4.8. 
Programmer’s note: Figures 14.2.3.4.4 through 14.2.3.4.8 will be spaghetti 
plots. 
14.2.3.5 
Urine p-Toluic Acid Tables 
Table 14.2.3.5.1 Urinary Excretion of p-Toluic Acid Following a Single 
Oral Dose of 50 mg SXC-2023 Administered Under Fasted 
Conditions (Cohort 1 - Treatment A) (Pharmacokinetic 
Population) 
Programmer’s note: Tables 14.2.3.5.1 through 14.2.3.5.8 will present urine p-
Toluic Acid data and will follow the same format as Tables 
14.2.1.5.1 through 14.2.1.5.8. 
14.2.3.6 
Urine p-Toluic Acid Figures 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 36 of 105 
Figure 14.2.3.6.1 Mean (SD) Cumulative Urine p-Toluic Acid Amounts 
Excreted Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
Figure 14.2.3.6.2 Mean Cumulative Urine p-Toluic Acid Amounts Excreted 
Following Administration of Single Oral Doses of 
SXC-2023 (Linear Scale) (Treatments A-G) 
(Pharmacokinetic Population) 
 
Programmer’s note: Figures 14.2.3.6.1 and 14.2.3.6.2 will present urine 
p-toluic acid data and will follow the same format as 
Figures 14.2.1.6.1 and 14.2.1.6.2. 
Programmer’s note: Figures 14.2.3.6.1 and 14.2.3.6.2 will present amount 
excreted (CumAe) versus the nominal end of the collection 
interval (0, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose). 
14.3 
Safety Data Summary Tables  
14.3.1 
Displays of Adverse Events 
Table 14.3.1.1 Treatment-emergent Adverse Event Frequency by Treatment 
– Number of Subjects Reporting the Event (% of Subject 
Dosed) (Safety Population) 
Table 14.3.1.2 Treatment-emergent Adverse Event Frequency by Treatment 
– Number of Adverse Events (% of Total Adverse Events) 
(Safety Population) 
Table 14.3.1.3 Treatment-emergent Adverse Event Frequency by Treatment, 
Severity, and Relationship to Study Drug – Number of 
Adverse Events (Safety Population) 
14.3.2 
Listings of Deaths, other Serious and Significant Adverse Events 
Table 14.3.2.1 Serious Adverse Events (Safety Population)  
 
14.3.3 
Narratives of Deaths, other Serious and Certain other 
Significant Adverse Events 
14.3.4 
Abnormal Laboratory Value Listing (each patient) 
Table 14.3.4.1 Out-of-Range Values and Recheck Results – Serum 
Chemistry (Safety Population) 


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Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 37 of 105 
Table 14.3.4.2 Out-of-Range Values and Recheck Results – Hematology 
(Safety Population) 
Table 14.3.4.3 Out-of-Range Values and Recheck Results – Urinalysis 
(Safety Population) 
Table 14.3.4.4 Clinically Significant Values and Recheck Results (Safety 
Population) 
14.3.5 
Displays of Other Laboratory, Vital Signs, Electrocardiogram, 
Physical Examination, and Other Safety Data 
Table 14.3.5.1.1 Clinical Laboratory Summary – Serum Chemistry (Safety 
Population) 
Table 14.3.5.1.2 Clinical Laboratory Change From Baseline – Serum 
Chemistry (Safety Population) 
Table 14.3.5.1.3 Clinical Laboratory Shift From Baseline – Serum 
Chemistry (Safety Population) 
Table 14.3.5.2.1 Clinical Laboratory Summary – Hematology (Safety 
Population) 
Table 14.3.5.2.2 Clinical Laboratory Change From Baseline – Hematology 
(Safety Population) 
Table 14.3.5.2.3 Clinical Laboratory Shift From Baseline – Hematology 
(Safety Population) 
Table 14.3.5.3.1 Clinical Laboratory Summary – Urinalysis (Safety 
Population) 
Table 14.3.5.3.2 Clinical Laboratory Change From Baseline – Urinalysis 
(Safety Population) 
Table 14.3.5.3.3 Clinical Laboratory Shift From Baseline – Urinalysis 
(Safety Population) 
Table 14.3.5.4.1   Vital Sign Summary (Safety Population)  
Table 14.3.5.4.2 Vital Sign Change From Baseline (Safety Population)  
Table 14.3.5.5.1 12-Lead Electrocardiogram Summary (Safety Population) 
Table 14.3.5.5.2 12-Lead Electrocardiogram Change From Baseline (Safety 
Population) 
Table 14.3.5.5.3 12-Lead Electrocardiogram Shift From Baseline (Safety 
Population) 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 38 of 105 
9.3 
Section 16 Data Listings 
Note: Hepatitis and HIV results that are provided by the clinical laboratory will not be 
presented in subject data listings and will not be included in any database transfer.  
Data listings are numbered following the ICH structure but may be renumbered as 
appropriate during the compilation of the TFLs for the CSR. The following is a list of 
appendix numbers and titles that will be included as data listings: 
16.1 
Study Information 
Appendix 16.1.9 
Statistical Methods 
Appendix 16.1.10.1 
Clinical Laboratory Reference Ranges 
16.2 
Subject Data Listings 
16.2.1 
Subject Discontinuation 
Appendix 16.2.1 
Subject Discontinuation (Safety Population) 
16.2.2 
Protocol Deviations 
Appendix 16.2.2 
Protocol Deviations 
16.2.3 
Subjects Excluded from Pharmacokinetic Analysis 
Appendix 16.2.3 
Subjects Excluded from Pharmacokinetic Analysis 
Note: Appendices 16.2.2 and 16.2.3 are generated in MS Word for inclusion 
in the study report. 
16.2.4 
Demographic Data 
Appendix 16.2.4.1 
Demographics (Safety Population) 
Appendix 16.2.4.2 
Physical Examination (Safety Population)  
Appendix 16.2.4.3 
Medical and Surgical History (Safety Population) 
Appendix 16.2.4.4 
Substance Use (Safety Population) 
16.2.5 
Compliance and/or Drug Concentration Data 
Appendix 16.2.5.1.1 Inclusion Criteria   
Appendix 16.2.5.1.2 Exclusion Criteria 
Appendix 16.2.5.2 
Subject Eligibility (Safety Population) 
Appendix 16.2.5.3.1 Check-in and Return Criteria  


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 39 of 105 
Appendix 16.2.5.3.2 Check-in and Return Responses (Safety Population) 
Appendix 16.2.5.4.1 Test Compound Description (Safety Population) 
Appendix 16.2.5.4.2 Test Compound Administration Times (Safety 
Population) 
Appendix 16.2.5.5 
Blood Draw Times (Safety Population) 
Appendix 16.2.5.6 
Urine Collection Times (Safety Population) 
Appendix 16.2.5.7 
Meal Times (Safety Population) 
Appendix 16.2.5.8 
Prior and Concomitant Medications (Safety Population) 
16.2.6 
Individual Pharmacokinetic Response Data 
Appendix 16.2.6.1 
Plasma SXC-2023 Concentrations Versus Time (Linear 
and Semi-Log Scale) for Subject # 
Appendix 16.2.6.2 
RBC SXC-2023 Concentrations Versus Time (Linear 
and Semi-Log Scale) for Subject # 
Appendix 16.2.6.3 
Urine SXC-2023 Amounts Excreted Versus Time 
(Linear Scale) for Subject # 
Appendix 16.2.6.4 
Percent of SXC-2023 Dose Excreted in urine Versus 
Time (Linear Scale) for Subject # 
Appendix 16.2.6.5 
Plasma NAC Concentrations Versus Time (Linear and 
Semi-Log Scale) for Subject # 
Appendix 16.2.6.6 
RBC NAC Concentrations Versus Time (Linear and 
Semi-Log Scale) for Subject # 
Appendix 16.2.6.7 
Urine NAC Amounts Excreted Versus Time (Linear 
Scale) for Subject # 
Appendix 16.2.6.8 
Plasma p-Toluic Acid Concentrations Versus Time 
(Linear and Semi-Log Scale) for Subject # 
Appendix 16.2.6.9 
RBC p-Toluic Acid Concentrations Versus Time 
(Linear and Semi-Log Scale) for Subject # 
Appendix 16.2.6.10 
Urine p-Toluic Acid Amounts Excreted Versus Time 
(Linear Scale) for Subject # 
16.2.7 
Adverse Events Listings 
Appendix 16.2.7.1.1 Adverse Events (I of II) (Safety Population) 
Appendix 16.2.7.1.2 Adverse Events (II of II) (Safety Population) 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 40 of 105 
Appendix 16.2.7.2 
Adverse Event Non-Drug Therapy (Safety Population) 
Appendix 16.2.7.3 
Adverse Event Preferred Term Classification (Safety 
Population) 
16.2.8 
Listings of Individual Laboratory Measurements and Other 
Safety Observations 
Appendix 16.2.8.1.1 Clinical Laboratory Report - Serum Chemistry (Safety 
Population)  
Appendix 16.2.8.1.2 Clinical Laboratory Report - Hematology (Safety 
Population) 
Appendix 16.2.8.1.3 Clinical Laboratory Report - Urinalysis (Safety 
Population) 
Appendix 16.2.8.1.4 Clinical Laboratory Report - Urine Drug Screening 
(Safety Population) 
Appendix 16.2.8.1.5 Clinical Laboratory Report - Comments (Safety 
Population) 
Appendix 16.2.8.2 
Vital Signs (Safety Population) 
Appendix 16.2.8.3 
12-Lead Electrocardiogram (Safety Population) 
 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                     28 February 2018                                                  Page 41 of 105 
10. TABLE AND FIGURE SHELLS  
The following table shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the tables that will be presented and included in the final report. Unless otherwise 
noted, all tables will be presented in Times New Roman font size 8. These tables will 
be generated off of the Celerion ADaM Model 2.1 and ADaM Implementation Guide 
1.1. 
  
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 42 of 105 
10.1 
In-text Summary Tables Shells 
In-text Table 10-1 will be in the following format: 
 
Table 10-1 
 
Summary of Disposition 
 
 
Randomized Treatment 
 
Disposition 
A 
B 
C 
… 
G 
Placebo 
Overall 
Enrolled 
XX (1000%) XX (100.0%) XX (100.0%) XX (100.0%) XX (100.0%) XX (100.0%) XX (100.0%) 
Completed 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
Discontinued Early 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
   <Reason1> 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
   <Reason2> 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
<AE =Adverse event > 
Subjects enrolled in the food effect cohort are summarized according to the treatment they were randomized to receive 
in Period 1.  
 
Source: Table 14.1.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_disp.sas  DDMMMYYYY  HH:MM 
 
 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 43 of 105 
In-text Table 11-1 will be in the following format: 
 
Table 11-1 
Demographic Summary  
 
 
Treatment 
 
Trait 
Category/Statistics 
A 
B 
C 
… 
G 
Placebo 
Overall 
Sex 
Male 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
 
Female 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
Race 
Asian 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
 
Black or African 
American 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
 
White 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
Ethnicity 
Hispanic or Latino 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
 
Not Hispanic or Latino XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
Age* (yrs) n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
BMI = Body mass index 
*Age is derived from birth date to date of first dose. 
Subjects enrolled in the food effect cohort are summarized according to the treatment they are randomized to receive in Period 
1. 
 
Source: Table 14.1.1.2 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_dem.sas  DDMMMYYYY  HH:MM 
 
Programmer Notes: Height (cm), Weight(cm), and BMI (kg/m²) will be also summarized in the table above. Weight will be 
summarized at screening.  
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 44 of 105 
In-text Tables 11-2, 11-5, 11-7, 11-8, 11-10, 11-11, 11-12, 11-14, and 11-15 will be in the following format:  
 
Table 11-2 Summary of Plasma SXC-2023 Pharmacokinetics Following Single Oral Doses of SXC-2023 Administered Under Fasted 
or Fed Conditions  
 
 
Pharmacokinetic Parameters 
Treatment <Y> 
Treatment <X> 
Param1 (units)   
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param2 (units)   
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param3 (units)   
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Param4 (units)  
XXX.X (XX.X) [n=xx] 
XXX.X (XX.X) [n=xx] 
Treatment <Y>: <Label for Second Treatment>  
Treatment <X>: <Label for First Treatment> 
AUCs and Cmax values are presented as geometric mean and geometric CV%. 
Tmax values are presented as median (min, max). 
Other parameters are presented as arithmetic mean (± SD).  
Source: Tables <XXXX> and <YYYY> 
  
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
The following plasma and RBC PK parameters (In-Text Tables 11-2, 11-5, 11-9, 11-12, 11-16, and 11-19) will be presented in the 
following order and with following units: AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), Cmax (ng/mL), Tmax (hr), Kel (1/hr), t½ (hr), CL/F 
(L/hr), and Vz/F (L). CL/F and Vz/F will not be presented for NAC and p-toluic acid plasma and RBC PK tables (In-text Tables 11-9, 
11-12, 11-16 and 11-19). 
• 
The following urine PK parameters (In-Text Tables 11-8, 11-15, and 11-22) will be presented in the following order and with following 
units: Ae0-72 (mg), CLr (L/hr or mL/hr), and %Fe (%). %Fe will not be presented for NAC and p-toluic acid urine PK tables (In-text 
Tables 11-15 and 11-22). 
• 
Summary statistics will be presented with same precision as defined in post-text shells.  
• 
Internal template: ITPar1 
 
 
Celerion Note: Per study design needs, the following changes are made to this table relative to Celerion’s standard shell: 6 columns will be 
presented instead of 2. Column headers will be: ‘50 mg Fasted’, ‘100 mg Fasted’, ‘200 mg Fasted’, ‘400 mg Fasted’, ‘800 mg Fasted’, and ‘XX mg 
Fed’. 
 
Program:  /CAXXXXX/sas_prg/pksas/intext-pk-tables.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_intext_pkparam.sas   DDMMMYYYY  HH:MM 
      
 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 45 of 105 
In-text Tables 11-3 and 11-6 will be in the following format: 
 
 
Table 11-3 Summary of Statistical Comparisons of Plasma SXC-2023 Pharmacokinetic Parameters Following Single Oral Doses of 
SXC-2023 Administered Under Fed Versus Fasted Conditions 
 
 
 
Parameter 
Treatment <X> (Test) 
Treatment <Y> 
(Reference) 
GMR (%) 
90% Confidence 
Interval 
Intra subject 
CV% 
Geometric LSMs 
n 
Geometric LSMs 
n 
param1 (units) 
XXX.X 
XX 
XXX.X 
XX 
XX.XX 
XX.XX - XX.XX 
X.XX 
param2 (units) 
XXX.X 
XX 
XXX.X 
XX 
XX.XX 
XX.XX - XX.XX 
X.XX 
param3 (units) 
XXX.X 
XX 
XXX.X 
XX 
XX.XX 
XX.XX - XX.XX 
X.XX 
Treatment <X>: <Label for Test Treatment>  
Treatment <Y>: <Label for Reference Treatment>  
Geometric least-squares means (LSMs) are calculated by exponentiating the LSMs derived from the ANOVA. 
Geometric Mean Ratio (GMR) = 100*(test/reference) 
Intra-subject CV% was calculated as 100 x square root(exp[MSE]-1), where MSE = Residual variance from ANOVA. 
Source: Table XXXX 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
The following PK parameters will be presented in the following order and with following units: AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), 
and Cmax (ng/mL); 
• 
n will be presented as an integer (with no decimal); 
• 
All statistics will be presented with same precision as defined in post-text shells;  
• 
The test treatment will be the fed condition and the reference treatment will be the fasted condition for the cohort selected for FE; 
• 
Treatment Labels will be updated depending on the cohort selected for FE; 
• 
Internal template: Table ITPStat1. 
 
 
Celerion Note: Per study design needs, the following changes are made to this table relative to Celerion’s standard shell: None. 
 
Program:  /CAXXXXX/sas_prg/pksas/intext-pk-tables.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_intext_pkparam.sas   DDMMMYYYY  HH:MM 
 
 
 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 46 of 105 
In-text Tables 11-4, 11-9, and 11-13 will be in the following format: 
 
 
 
                                                                                                                     
Table 11-4  Dose Proportionality Analysis of Plasma SXC-2023 Pharmacokinetic Parameters Following Single Oral Doses of 
SXC-2023 Administered Under Fasted Conditions 
 
                        
Pharmacokinetic 
Parameters 
Estimate of Slope 
(b) 
Standard 
Error 
95% Confidence Interval 
for Slope 
Param1 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
Param2 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
Param3 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
                       --------------------------------------------------------------------------------------------------- 
Presentation of Data: 
• 
Slope will be presented to 4 decimal places  
• 
Standard error will be presented to 4 decimal places 
• 
95% CI will be presented to 4 decimal places 
• 
Internal template: CPDProp1 
 
 
 
Notes for Generating the Actual Table: 
 
Programmers Note: 
PK Parameters are AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), and Cmax (ng/mL) 
Biostat Note:   
Please use the footnote below if it is power model: 
Parameters were ln-transformed prior to analysis.        
The following statistical model using PROC MIXED of SAS was used to test dose proportionality: Parameter = a * Dose^b which was 
equivalent to ln(Parameter) = ln(a) + b[ln(Dose)] 
Dose proportionality is not rejected if the 95% CI for b contains 1. 
 
 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: None 
Program:  /CAXXXXX/sas_prg/pksas/doseprop-mixed.sas    
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_dosepropmixed.sas   DDMMMYYYY  HH:MM 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 47 of 105 
In-text Table 12-1 will be in the following format: 
 
Table 12-1 
Treatment-Emergent Adverse Event Frequency by Treatment – Number of Subjects Reporting the Event (% of 
Subjects Dosed)  
 
 
Treatment 
 
Adverse Event* 
A 
B 
C 
D 
… 
G 
Placebo 
Overall 
Number of Subjects 
Dosed 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
Number of Subjects 
With TEAEs 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
Number of Subjects 
Without TEAEs 
XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) XX (XX%) 
System Organ Class 1      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
 
Preferred Term 1      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
 
Preferred Term 2      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
System Organ Class 2      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
 
Preferred Term 1      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
 
Preferred Term 2      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%) 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
*Adverse events are coded using MedDRA® Version 20.0. 
If a subject has 2 or more clinical adverse events, the subject is counted only once within a category. The same subject may 
appear in different categories. 
TEAEs = Treatment-emergent adverse events 
 
Source: Table 14.3.1.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_ae.sas  DDMMMYYYY  HH:MM 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 48 of 105 
10.2 
Figures Shells 
In-text Figures 11-1 through 11-7 and Figures 14.2.1.2.2, 14.2.1.4.2, 14.2.1.6.2, 14.2.1.6.4, 14.2.2.2.2, 14.2.2.4.2, 14.2.2.6.2, 
14.2.3.2.2, 14.2.3.4.2, and 14.2.3.6.2 will be in the following format (Internal template: PFPConc2): 
 
Figure 11-1 Arithmetic Mean Plasma SXC-2023 Concentration-Time Profiles Following Administration of Single Oral Doses of 
SXC-2023 Under Fasted or Fed Conditions 
 
 
 
 


Promentis Pharmaceuticals, Inc. 
SXC-2023, PRO-101 
Celerion, Clinical Study Report No. CA22427 
 
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 49 of 105 
Figures 14.2.1.2.1, 14.2.1.4.1, 14.2.1.6.1, 14.2.1.6.3, 14.2.2.2.1, 14.2.2.4.1, 14.2.2.6.1, 14.2.3.2.1, 14.2.3.4.1, and 14.2.3.6.1 will be in 
the following format (Internal template: PFPConc1): 
 
 
Figure 14.2.1.2.1 Mean (SD) Plasma SXC-2023 Concentration Versus Time Profiles Following Administration of Single Oral Doses 
of SXC-2023 (Linear Scale) (Treatments A-G - Pharmacokinetic Evaluable Population) 
 
 


  
Statistical Analysis Plan                                                                                  28 February 2018                                                                                   Page 50 of 105 
Figures 14.2.1.2.3, 14.2.1.4.3, 14.2.2.2.3, 14.2.2.4.3, 14.2.3.2.3, and 14.2.3.4.3 will be in the following format (Internal template: 
PFPConc3): 
 
Figure 14.2.2.3 Mean Plasma SXC-2023 Concentration Versus Time Profiles Following Administration of Single Oral Doses of SXC 
2023 (Semi-Log Scale) (Treatments A-G Pharmacokinetic Evaluable Population) 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 51 of 105 
Notes for Generating the Actual Mean Figure: 
 
• 
Legends will be: ‘50 mg Fasted’, ‘100 mg Fasted’, ‘200 mg Fasted’, ‘400 mg Fasted’, ‘800 mg Fasted’, and ‘XX mg Fed’; 
• 
Y axis label will be Plasma <Analyte> Concentration (ng/mL)for Figures 11-1, 11-4, and 11-6, Amount Excreted (mg) for Figures 11-2, 
11-5, and 11-7, or Percent of Dose Excreted (%)for Figure 11-3; 
• 
X axis label will be “Hours From Dosing”. 
• 
3 treatments will be shifted to the right for ease of reading 
 
Program:  /CAXXXXX/sas_prg/pksas/meangraph.sas   
 
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_meangraph.sas    
DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 52 of 105 
Figures 14.2.1.2.4 through 14.2.1.2.10, 14.2.1.4.4 through 14.2.1.4.8, 14.2.2.2.4 through 14.2.2.2.10, 14.2.2.4.4 through 14.2.2.4.8, 
14.2.3.2.4 through 14.2.3.2.10, and 14.2.3.4.4 through 14.2.3.4.8 will be in the following format (Internal template: PFPConc6): 
 
Figure 14.2.2.1 
Superimposed Plasma SXC-2023 Concentration Versus Time Profiles Following Administration a Single Oral 
Dose of 50 mg SXC-2023 Administered Under Fasted Conditions (Treatment A)  (Linear Scale) 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 53 of 105 
Notes for Generating the Actual Spaghetti Plots Figure: 
 
• 
All profiles will be presented with the same line type (with or without color) 
• 
Y axis label will be <Matrix> <Analyte> Concentration (<units>) 
• 
X axis label will be “Hours From Dosing” 
• 
Reference line will not be included for the LOQ  
• 
Mean or median values will not be presented, the descriptive footnote will be removed and no median or mean (red stars) will be 
presented – only individual lines representing subject values will be shown 
 
 
Program:  /CAXXXXX/sas_prg/pksas/spaggraph.sas   
 
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_spaggraph.sas    
DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 54 of 105 
10.3 
Section 14 Summary Tables Shells 
 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 55 of 105 
Table 14.1.1.1 will be in the following format: 
 
                                                                                                Part 1 of X 
                        Table 14.1.1.1  Summary of Disposition (Safety Population)                                                   
                                                                                                                            
                                              Randomized Treatment 
                    ---------------------------------------------------------------------- 
                                                                                   
Category                 A           B           C           …           G       Placebo      Overall        
-------------------------------------------------------------------------------------------------------- 
Enrolled             XX (100%)   XX (100%)   XX (100%)   XX (100%)   XX (100%)   XX (100%)   XX (100%)    
Completed              X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)       
Discontinued Early     X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)       
  <Reason1>            X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)       
  <Reason2>            X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)      X (X%)       
 
 
 
 
Treatment A: < >                                                                                                         
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
<AE = Adverse event> 
Subjects included in the food effect cohort are summarized according to the treatment they were randomized to 
receive in Period 1.  
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM      
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 56 of 105 
Table 14.1.1.2 will be in the following format: 
                                                                                                    Page 1 of X                   
                         Table 14.1.1.2  Demographic Summary (Safety Population)               
                                                                                                                                      
                                                       Treatment 
                             ------------------------------------------------------------ 
                                                                                  
Trait                             A         B         C        …          G      Placebo   Overall 
---------------------------------------------------------------------------------------------------- 
Sex             Male           X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                Female         X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                                                                                                                                      
Race            Asian          X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                Black or       X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                African 
                American 
                White          X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
 
Ethnicity       Hispanic       X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                or Latino 
                Not Hispanic   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)   X (XX%)    
                or Latino 
                Latino 
                                                                                                                                      
Age* (yrs)      n                  X          X         X         X        X         X         X       
                Mean             X.X        X.X       X.X       X.X      X.X       X.X       X.X       
                SD              X.XX       X.XX      X.XX      X.XX     X.XX      X.XX      X.XX       
                Minimum           XX         XX        XX        XX       XX        XX        XX       
                Median           X.X        X.X       X.X       X.X      X.X       X.X       X.X       
                Maximum           XX         XX        XX        XX       XX        XX        XX       
 
Treatment A: < >   
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Age is derived from birth date to date of first dose.  
Subjects included in the food effect cohort are summarized according to the treatment they were randomized to receive 
in Period 1.  
BMI = Body mass index 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 57 of 105 
Programmer Notes: Weight (kg), Height (cm) and BMI (kg/m2) will also be summarized in the table above. Weight will be 
summarized at screening.  
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 58 of 105 
Concentration tables: Tables 14.2.1.1.1 through 14.2.1.1.8, Tables 14.2.1.3.1 through 14.2.1.3.6, Tables 14.2.2.1.1 through 14.2.2.1.8, 
Tables 14.2.2.3.1 through 14.2.2.3.6, Tables 14.2.3.1.1 through 14.2.3.1.8, and Tables 14.2.3.3.1 through 14.2.3.3.6 will be in the 
following format: 
 
Table 14.2.1.1.1 Plasma SXC-2023 Concentrations ng/mL) Following a Single Oral Dose of 50 mg SXC-2023 Administered Under Fasted Conditions 
(Cohort 1 - Treatment A) (Pharmacokinetic Population) 
 
Subject 
Treatment 
Study --------------------------------- Sample Times (hr) -------------------------------- 
 
Number 
Sequence Period Predose 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
------------------------------------------------------------------------------------------------------------------------------- 
X 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
X 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
X 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
------------------------------------------------------------------------------------------------------------------------------- 
n 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
CV% 
 
 
. 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
------------------------------------------------------------------------------------------------------------------------------- 
For the calculation of summary statistics, values that are below the limit of quantitation (BLQ) of XX are treated as 0  
before the first quantifiable concentration and as missing elsewhere. 
. = Value missing or not reportable.  
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
Concentrations will be presented to same precision as in bio data.  
Summary statistics presentation with respect to the precision of the bio data: n = integer; Mean and Median +1; SD and SEM +2, Min and Max 
+0, CV% to 1 decimal 
Internal template: Table CPConc1 
 
Programmer Note:  
PK Time points are from Protocol: i.e. predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, and 72 hours 
postdose. 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: Columns ‘Treatment Sequence’ and ‘Study 
Period’ will be removed except for the food effect cohort where the ‘Study Period’ column will be presented. 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 59 of 105 
Program:  /CAXXXXX/sas_prg/pksas/pk-conc-tables.sas    
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/pk-conc-tables-sig.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_conc.sas   
 
DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 60 of 105 
PK parameter tables: Tables 14.2.1.1.9 through 14.2.1.1.15, Tables 14.2.1.3.7 through 14.2.1.3.11, Tables 14.2.2.1.9 through 14.2.2.1.15, 
Tables 14.2.2.3.7 through 14.2.2.3.11, Tables 14.2.3.1.9 through 14.2.3.1.15, and Tables 14.2.3.3.7 through 14.2.3.3.11 will be in the 
following format: 
 
Page X of X 
Table 14.2.1.1.9  Plasma SXC-2023 Pharmacokinetic Parameters Following a Single Oral Dose of 50 mg SXC-2023 Administered Under Fasted Conditions 
(Cohort 1 - Treatment A) (Pharmacokinetic Evaluable Population) 
  
                                                      ------------------------------------ Parameters ----------------------------- 
Subject 
Treatment 
Study 
param1 
param2 
param3 
param4 
param5 
param6 
Number 
Sequence 
Period 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
    -------------------------------------------------------------------------------------------------------------------------------- 
X 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
X.XX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
X 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
    -------------------------------------------------------------------------------------------------------------------------------- 
n 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
SD 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
CV% 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Median 
 
 
XX.XX 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Maximum 
 
 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Geom Mean 
 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Geom CV% 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    -------------------------------------------------------------------------------------------------------------------------------- 
         . = Value missing or not reportable. 
 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
PK Parameters will be presented in the following order and with following units: AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), Cmax (ng/mL), 
Tmax (hr), Kel (1/hr), t½ (hr), CL/F (L/hr), and Vz/F (L). CL/F and Vz/F will not be presented for plasma and RBC NAC and p-toluic 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 61 of 105 
acid PK tables (Tables 14.2.2.1.8 through 14.2.2.1.13, Tables 14.2.2.3.6 through 14.2.2.3.9, Tables 14.2.3.1.8 through 14.2.3.1.13, 
and Tables 14.2.3.3.6 through 14.2.3.3.9); 
• 
n will be presented as an integer (with no decimal); 
• 
Parameter values for Cmax will be presented with the precision of the bio data,  
• 
Parameter values for AUCs will be presented with 3-4 significant figures (to be determined by the PKist once bio data are received), 
• 
Parameter values for Kel,Vz/F, and CL/F will be presented with 3 significant figures,  
• 
Values for time-based parameters (i.e. Tmax and t1/2) will be presented with 2 decimals,  
• 
Summary statistics for all parameters will be presented as: Mean, Median, and Geom Mean +1; SD and SEM +2, Min and Max +0;  
• 
CV% and Geom CV% for all parameters will be presented with 1 decimal; 
• 
Internal template: Table CPPar1. 
 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: Columns ‘Treatment Sequence’ and ‘Study 
Period’ will be removed except for the food effect cohort where the ‘Study Period’ column will be presented.> 
 
Program:  /CAXXXXX/sas_prg/pksas/pk-tables.sas   
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_pkparam.sas   DDMMMYYYY  HH:MM 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 62 of 105 
Kel Interval tables: Tables 14.2.1.1.16, 14.2.1.3.12, 14.2.2.1.16, 14.2.2.3.12, 14.2.3.1.16, and 14.2.3.3.12 will be in the following 
format: 
 
                                                                                                                               Page X of X 
                        Table 14.2.1.1.16  Intervals (Hours) Used for Determination of Plasma SXC 2023 Kel Values (Pharmacokinetic Population) 
 
 
Subject 
Number 
Treatment 
Interval 
R2 
n 
                      ----------------------------------------------------------------------- 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
X 
X 
XX.X - XX.X 
X.XXX 
X 
                      ----------------------------------------------------------------------- 
                        Treatment <X>: <Label for First Treatment> 
                        Treatment <Y>: <Label for Second Treatment> 
                        R2 = Coefficient of determination  
                        n = Number of points used in Kel calculation 
                        . = Kel value not reportable. 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
Interval start and stop times will be presented to 1 decimal or 3 sig figures min; 
• 
R2 will be presented to 3 decimals; 
• 
n will be presented as an integer (with no decimal) 
• 
Internal template: CPKel2 
 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: 6 treatments will be presented 
 
Program:  /CAXXXXX/sas_prg/pksas/kel-tables-parallel.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_kel.sas    
DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 63 of 105 
Statistical comparison (ANOVA) tables: Tables 14.2.1.1.17 and 14.2.1.3.13 will be in the following format: 
 
                                                                                                                               Page X of X 
Table 14.2.1.1.17  Statistical Comparisons of Plasma SXC-2023 Pharmacokinetic Parameters: Fed Versus Fasted Conditions (Cohort X - Pharmacokinetic 
Evaluable Population) 
 
 
 
Treatment 
------- Geometric LSMs ------- 
Geometric 
Mean 
90 %  
Intra-subject 
Parameter 
(unit) 
<X> 
(n) 
<Y> 
(n) 
Ratio 
Confidence Intervals 
CV% 
--------------------------------------------------------------------------------------------------------------------------------------------------- 
Param1 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
Param2 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
Param3 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
--------------------------------------------------------------------------------------------------------------------------------------------------- 
    Treatment <Y>: <Label for Second Treatment> (test) 
    Treatment <X>: <Label for First Treatment> (reference) 
    Parameters were ln-transformed prior to analysis.  
    Geometric least-squares means (LSMs) are calculated by exponentiating the LSMs from ANOVA. 
    Geometric Mean Ratio = 100*(test/reference)  
    Intra-subject CV% = 100 x (square root (exp[MSE]-1), where MSE = Residual variance from ANOVA. 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
PK parameters will be: AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), and Cmax (ng/mL); 
• 
Geometric LSMs be presented to same precision as Mean in the PK parameter table CPPar1; 
• 
Geometric Mean Ratio, 90% CI and intra-subject CV% will be presented to 2 decimal places; 
• 
Internal template: CPStat1 
 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: None 
 
Program:  /CAXXXXX/sas_prg/pksas/stats-tables-mixed.sas   DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_statsmixed.sas   DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 64 of 105 
Dose proportionality analysis tables: Tables 14.2.1.1.18, 14.2.2.1.17, and 14.2.3.1.17 will be in the following format: 
 
                                                                                                                       Page X of X 
Table 14.2.1.1.18.  Dose Proportionality Analysis of Plasma SXC-2023 Pharmacokinetic Parameters Under Fasted Conditions (Pharmacokinetic 
Evaluable Population) 
 
Pharmacokinetic 
Parameters 
Estimate of Slope 
(b) 
Standard 
Error 
95% Confidence Interval 
for Slope 
                       --------------------------------------------------------------------------------------------------- 
Param1 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
Param2 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
Param3 
X.XXXX 
X.XXXX 
X.XXXX - X.XXXX 
                       --------------------------------------------------------------------------------------------------- 
Presentation of Data: 
• 
Slope will be presented to 4 decimal places  
• 
Standard error will be presented to 4 decimal places 
• 
95% CI will be presented to 4 decimal places 
• 
Internal template: CPDProp1 
 
 
 
Notes for Generating the Actual Table: 
 
Programmers Note: 
PK Parameters are AUC0-t (ng*hr/mL), AUC0-inf ng*hr/mL), and Cmax (ng/mL) 
Biostat Note:   
Please use the footnote below if it is power model: 
Parameters were ln-transformed prior to analysis.        
The following statistical model using PROC MIXED of SAS was used to test dose proportionality: Parameter = a * Dose^b which was 
equivalent to ln(Parameter) = ln(a) + b[ln(Dose)] 
Dose proportionality is not rejected if the 95% CI for b contains 1. 
 
 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: None 
Program:  /CAXXXXX/sas_prg/pksas/doseprop-mixed.sas    
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_dosepropmixed.sas   DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 65 of 105 
Urine excretion tables: Tables 14.2.1.5.1 through 14.2.1.5.8, Tables 14.2.2.5.1 through 14.2.2.5.8, and Tables 14.2.3.5.1 through 14.2.3.5.8 
will be in the following format: 
                                                                                                                               Page X of X 
 
Table 14.2.1.5.1  Urinary Excretion of SXC-2023 Following a Single Oral Dose of 50 mg SXC-2023 Administered Under Fasted Conditions (Cohort 1 - 
Treatment A) (Pharmacokinetic Population) 
 
 
 
  
--------------------------------------------- Parameters ------------------------------------------- 
  
Predose 
 
X – X Hours 
---------------------------------------------   ----------------------   ------------------------------------------------------------------------------ 
Subject 
Treatment 
Study  
Conc 
Vol  
Conc 
Vol 
Ae 
CumAe 
%Dose Cum%Dose 
CLr 
Number 
Sequence 
Period  (units) (units)  (units) (units) (units) (units) 
(%) 
(%) (units) 
------------------------------------------------------------------------------------------------------------------------------------------------------- 
X 
XXX 
X  
X.XX 
X.XX  
XX.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X 
XXX 
X  
X.XX 
X.XX  
XX.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X 
XXX 
X  
X.XX 
X.XX  
XX.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
------------------------------------------------------------------------------------------------------------------------------------------------------- 
n 
 
  
X 
X  
X 
X 
X 
X 
X 
X 
X 
Mean 
 
  
X.XXX 
X.XXX  
XX.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
SD 
 
  
X.XXXX 
X.XXXX  XX.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
CV% 
 
  
X.X 
X.X  
XX.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
SEM 
 
  
X.XXXX 
X.XXXX  XX.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
X.XXXX 
Minimum 
 
  
X.XX 
X.XX  
XX.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Median 
 
  
X.XXX 
X.XXX  
XX.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
Maximum 
 
  
X.XX 
X.XX  
XX.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
Geom Mean 
 
  
X.XXX 
X.XXX  
XX.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
Geom CV% 
 
  
X.X 
X.X  
XX.X 
X.X 
X.X 
X.X 
X.X 
X.X 
X.X 
------------------------------------------------------------------------------------------------------------------------------------------------------- 
  . = Value missing or not reportable. 
 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
• 
Concentrations and amounts will be presented to same precision as the bio concentration data. Volume will be presented to same 
precision as on the CRF. Cum%Dose will be presented to 2 decimal places. Clr and all other parameters will be presented to 3 
significant figures. 
• 
Summary statistics presentation: n = integer; Mean Median and Geom Mean +1; SD and SEM +2, Min/Max +0, CV% and Geom CV% to 1 decimal. 
 
Programmers Note:  
Intervals are predose, and 0-1, 1-2, 2-4, 4-8, 8-12, 12-24, 24-48, and 48-72 hours postdose, and 0-72 (Overall). 
PK Parameters for each postdose interval are: Conc, Vol, Ae, CumAe, %Dose, Cum%Dose; predose: Conc, Vol, Overall: CumAe, Cum%Dose, CLr 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 66 of 105 
Internal template: Appendix Table C(A)UPar3 
 
Per study design needs, the following changes are made to this table relative to Celerion standard: Columns ‘Treatment Sequence’ and ‘Study 
Period’ will be removed except for the food effect cohort where the ‘Study Period’ column will be presented. 
 
Notes for preparation of standard programs (to be deleted after standard programs are updated):  
Update standard program name to include C(A)UPar3 shell name  
 
Program:  DM_PX:[HLXXXXX.PKSAS]URINE-CONC-TABLES.SAS  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 67 of 105 
 
Table 14.3.1.1 will be in the following format: 
Page 1 of X           
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Treatment – Number of Subjects Reporting the Event (% of 
Subjects Dosed) (Safety Population) 
 
                                                              Treatment 
                                  ---------------------------------------------------------------------------                         
Adverse Event* 
A          B          C           D          …         G       Placebo    Overall   
----------------------------------------------------------------------------------------------------------------------- 
Number of Subjects Dosed          XX (XXX%)  XX (XXX%)  XX (XXX%)  XX (XXX%)  XX (XXX%)  XX (XXX%)  XX (XXX%)  XX(XXX%) 
Number of Subjects With TEAEs      X (  X%)   X ( XX%)   X ( XX%)   X ( XX%)   X (XXX%)   X (XXX%)   X (XXX%)   X(XXX%) 
Number of Subjects Without TEAEs  XX ( XX%)  XX ( XX%)  XX ( XX%)  XX ( XX%)  XX (XXX%)  XX (XXX%)  XX (XXX%)  XX(XXX%) 
----------------------------------------------------------------------------------------------------------------------- 
Eye disorders                      X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Vision blurred                X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
Gastrointestinal disorders         X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Dyspepsia                     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Nausea                        X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
Musculoskeletal and connective     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
  tissue disorders 
     Back pain                     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Muscle cramps                 X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Musculoskeletal pain          X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Adverse events are coded using MedDRA Version 20.0. 
If a subject has 2 or more clinical adverse events, the subject is counted only once within a category. The same 
subject may appear in different categories. 
TEAEs = Treatment-emergent adverse events 
 
Programmer Notes: Should all treatments not be able to fit on the same page, then present the following treatments on a 
separate page: E, F, G, Placebo, Overall. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM          
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 68 of 105 
Tables 14.3.1.2 will be in the following format: 
 
Page 1 of X         
Table 14.3.1.2 Treatment-Emergent Adverse Event Frequency by Treatment –Number of Adverse Events (% of Total Adverse 
Events) (Safety Population) 
 
                                                              Treatment 
                                  ---------------------------------------------------------------------------                         
Adverse Event* 
A          B          C           D          …         G        Placebo   Overall 
----------------------------------------------------------------------------------------------------------------------- 
Number of TEAEs                    X (100%)   X (100%)   X (100%)   X (100%)   X (100%)   X (100%)   X (100%)   X(100%) 
----------------------------------------------------------------------------------------------------------------------- 
Eye disorders                      X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Vision blurred                X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
Gastrointestinal disorders         X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Dyspepsia                     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Nausea                        X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
Musculoskeletal and connective     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
  tissue disorders 
     Back pain                     X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Muscle cramps                 X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
     Musculoskeletal pain          X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X (  X%)   X(  X%) 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Adverse events are coded using MedDRA Version 20.0. 
TEAEs = Treatment-emergent adverse events 
 
 
Programmer Notes: Should all treatments not be able to fit on the same page, then present the following treatments on a 
separate page: E, F, G, Placebo, Overall. 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 69 of 105 
Table 14.3.1.3 will be in the following format: 
 
                                                                                                            Page 1 of X 
Table 14.3.1.3 Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship 
to Study Drug - Number of Adverse Events (Safety Population) 
                                                                                                                          
                               Number of 
                               Subjects Number   Severity Grade**                Relationship to Study Drug 
                               With     of    ----------------------- ------------------------------------------------- 
   Adverse Event*   Treatment  TEAEs    TEAEs   1     2     3     4    Unrelated  Unlikely Possibly  Probably  Likely   
   -------------------------------------------------------------------------------------------------------------------- 
   Abdominal pain        A     X        X       X     X     X     X       X          X        X         X        X    
   Constipation          F     X        X       X     X     X     X       X          X        X         X        X 
   Dry throat            B     X        X       X     X     X     X       X          X        X         X        X 
   Dysmenorrhoea         C     X        X       X     X     X     X       X          X        X         X        X 
   Dyspepsia             B     X        X       X     X     X     X       X          X        X         X        X 
   Headache              A     X        X       X     X     X     X       X          X        X         X        X 
                         E     X        X       X     X     X     X       X          X        X         X        X 
   Myalgia               G     X        X       X     X     X     X       X          X        X         X        X 
   Nasal congestion      C     X        X       X     X     X     X       X          X        X         X        X 
   Skin laceration       F     X        X       X     X     X     X       X          X        X         X        X 
   -------------------------------------------------------------------------------------------------------------------- 
   Treatment A                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment B                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment C                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment D                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment E                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment F                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment F                 X        X       X     X     X     X       X          X        X         X        X 
   Treatment Placebo           X        X       X     X     X     X       X          X        X         X        X 
   Overall                     X        X       X     X     X     X       X          X        X         X        X 
   -------------------------------------------------------------------------------------------------------------------- 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Adverse events are coded using MedDRA Version 20.0. 
** Severity Grade: 1 = Mild, 2 = Moderate, 3 = Severe or medically significant but not immediately life-threatening,  
4 = Life-threatening consequences   


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 70 of 105 
TEAEs = Treatment-emergent adverse events 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY HH:MM   
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 71 of 105 
Table 14.3.2.1 will be in the following format: 
 
Table 14.3.2.1 Serious Adverse Events (Safety Population)  
 
-------------------------------------------------------------------------------------------------------------------------------------------- 
 
 
 
Programmer Note: Will match 16.2.7 or contain the following statement: “There were no serious adverse events recorded during the study.” 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 72 of 105 
Tables 14.3.4.1 to 14.3.4.3 will have the following format: 
Page 1 of X 
 
Table 14.3.4.1  Out-of-Range Values and Recheck Results - Serum Chemistry (Safety Population) 
  
                                                                             Parameter1  Parameter2   Parameter3  Parameter4  Parameter5  
         Subject Age#/   Study                                                 <Range>     <Range>      <Range>      <Range>    <Range>   
 Cohort  Number  Sex    Period  Treatment  Day   Hour    Date       Time       (Unit)      (Unit)       (Unit)      (Unit)     (Unit)   
 ----------------------------------------------------------------------------------------------------------------------------------------- 
   X       X     XX/X   Screen              .      .     DDMMMYYYY  HH:MM:SS    XX HN                                           XX HN  
                          1        X       -X   -XX.XX   DDMMMYYYY  HH:MM:SS    XX LY-      XX LN                     XX LYR+            
                       Recheck                           DDMMMYYYY  HH:MM:SS                                          XX              
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
# Age is calculated at the time of first dosing. F = Female, M = Male 
H = Above reference range, L = Below reference range                                                                     
Computer: N = Not clinically significant, Y = Clinically significant                                                           
PI Interpretation: - = Not clinically significant, R = Recheck requested, ^ = Will be retested later, + = Clinically significant 
          
 
Programmer Notes:  Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early termination records 
chronologically with other scheduled assessments and rechecks. Recheck should be sorted with the scheduled time point the 
recheck is for.  
 
Clinically significant lab values generally will be captured as AEs, some of which the PI may indicate in Appendix 
16.2.8.1.6 lab comments (as per GPG.03.0028 sections 2.9 and 2.10). Derive an additional flag for PI flag -/+ based on 
comments (i.e. NCS/CS). Present this derived 4th column in all tables, and list only PI-determined out-of-range clinically 
significant lab values in Table 14.3.4.5.  
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM          
Page 1 of X 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 73 of 105 
 
                           Table 14.3.4.4  Clinically Significant Values and Recheck Results (Safety Population) 
 
          Subject  Age#/ Study                                                                                                     
   Cohort Number   Sex   Period  Treatment  Day  Hour  Date       Time      Department     Test             Result    Reference Range   Unit      
   ---------------------------------------------------------------------------------------------------------------------------------------- 
     X     X      XX/X   X        X       1  -X.XX  DDMMMYYYY  HH:MM:SS  Serum Chemistry  Cholesterol      XXX           X – X         mg/dL  
                                          2  XX.XX  DDMMMYYYY  HH:MM:SS  Serum Chemistry  Cholesterol      XXX  HYR+     X – X         mg/dL    
                                          3  XX.XX  DDMMMYYYY  HH:MM:SS  Serum Chemistry  Cholesterol      XXX  HY+      X – X         mg/dL     
                                          4  XX.XX  DDMMMYYYY  HH:MM:SS  Serum Chemistry  Cholesterol      XXX  HN       X – X         mg/dL  
 
 
 
 
 
 
 
 
 
                                                                                                                               
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
# Age is calculated at the time of first dosing. F = Female, M = Male 
H = Above reference range                                                                     
Computer: Y = Clinically significant                                                           
PI Interpretation: R = Recheck requested, + = Clinically significant  
 
 
Programmer Notes: All time points for a subject/test with at least one value deemed as CS by the PI will be presented in this table. 
If there were no CS values as deemed by PI (i.e., no “CS” or “Clinically Significant” in the PI comment field in the 
laboratory dataset), then this table will contain the following statement: “There were no laboratory values documented as 
clinically significant by the PI in the study.” 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 74 of 105 
Tables 14.3.5.1.1, 14.3.5.1.2, 14.3.5.2.1, 14.3.5.2.2, 14.3.5.3.1, and 14.3.5.3.2 will be in the following format: 
 
Page 1 of X 
Table 14.3.5.1.1  Clinical Laboratory Summary - Serum Chemistry (Safety Population) 
                                                                                             
                                                                                      Treatment 
                         Reference   Time                    --------------------------------------------------------- 
Laboratory Test (unit)   Range       Point       Statistic        A       B       C       D       …       G    Placebo 
---------------------------------------------------------------------------------------------------------------------- 
Testname (unit)          < - >       Baseline*   n                X       X       X       X       X       X         X 
                                                 Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                                 Minimum         XX      XX      XX      XX      XX      XX        XX 
                                                 Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                                     Day 2       n                X       X       X       X       X       X         X 
                                                 Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                                 Minimum         XX      XX      XX      XX      XX      XX        XX 
                                                 Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                                     Day 4       n                X       X       X       X       X       X         X 
                                                 Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                                 Minimum         XX      XX      XX      XX      XX      XX        XX 
                                                 Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                                 Maximum         XX      XX      XX      XX      XX      XX        XX 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Baseline is the last non-missing assessment prior to dosing (Day -1 Check-in), including rechecks and unscheduled 
assessments. 
# = Lowest of the lower ranges and highest of the higher ranges are used. Refer to Appendix 16.1.10.1 for the 
breakdown. 
  


  
Statistical Analysis Plan                                                                            28 February 2018 
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Programmer Notes: Similar for all time points and laboratory tests. For the change from baseline tables 14.3.5.1.2, 
14.3.5.2.2, and 14.3.5.3.2, please remove the baseline time point, keep the baseline definition footnote and change the 
‘Treatment’ header to ‘Change From Baseline’. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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Tables 14.3.5.1.3, 14.3.5.2.3, and 14.3.5.3.3 will be in the following format: 
 
Page 1 of X 
 
      Table 14.3.5.1.3  Clinical Laboratory Shift From Baseline - Serum Chemistry (Safety Population)                                 
                                                     
                                                           Baseline* L       Baseline* N         Baseline* H      
                                                      ------------------  -----------------  -----------------      
                                                            Postdose          Postdose             Postdose   
                                                      ------------------  -----------------  -----------------     
Laboratory Test (unit)   Treatment      Time Point        L    N     H        L    N    H        L    N    H 
-------------------------------------------------------------------------------------------------------------- 
Testname (unit)              A            Day 2           X    XX    X        X   XX    X        X    XX   X 
                                          Day 4           X    XX    X        X   XX    X        X    XX   X 
                             B            Day 2           X    XX    X        X   XX    X        X    XX   X 
                                          Day 4           X    XX    X        X   XX    X        X    XX   X 
                           
                           < - >           
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Baseline is the last non-missing assessment prior to dosing (Day -1 Check-in), including rechecks and unscheduled 
assessments. 
N = Within reference range, L = Below reference range, H = Above reference range 
 
Programmer Notes: Similar for all time points and laboratory tests. For urinalysis, the following footnote is used 
since the categories of N and O will be used instead of L, N, H: N = Within reference range, O = Outside reference 
range 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab prograname.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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Tables 14.3.5.4.1 and 14.3.5.4.2 will be in the following format: 
Page 1 of X 
Table 14.3.5.4.1  Vital Sign Summary (Safety Population) 
                                                                                             
                                                                         Treatment 
                    Time                        --------------------------------------------------------- 
Vital Sign (unit)   Point           Statistic        A       B       C       D       …       G    Placebo 
--------------------------------------------------------------------------------------------------------- 
Testname (unit)     Baseline*       n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                    Day 1 Hour 2    n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                    Day 1 Hour 4    n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Baseline is the last non-missing assessment prior to dosing (Predose), including rechecks and unscheduled 
assessments. 
Programmer Notes: Similar for all time points and vital signs. The following time points will be summarized: Baseline, 
Day 1 Hour 2, Day 1 Hour 4, Day 2, Day 3, Day 4, and Follow-Up. For the change from baseline table 14.3.5.4.2, please 
remove the baseline time point, keep the baseline definition footnote and change the ‘Treatment’ header to ‘Change From 
Baseline’. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM  
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 78 of 105 
 Tables 14.3.5.5.1 and 14.3.5.5.2 will be in the following format: 
 
Page 1 of X 
Table 14.3.5.5.1  12-Lead Electrocardiogram Summary (Safety Population) 
                                                                                             
                                                                         Treatment 
                    Time                        --------------------------------------------------------- 
Parameter (unit)    Point           Statistic        A       B       C       D       …       G    Placebo 
--------------------------------------------------------------------------------------------------------- 
Testname (unit)     Baseline*       n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                    Day 1 Hour 2    n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
 
                    Day 2           n                X       X       X       X       X       X         X 
                                    Mean           X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    SD            X.XX    X.XX    X.XX    X.XX    X.XX    X.XX      X.XX 
                                    Minimum         XX      XX      XX      XX      XX      XX        XX 
                                    Median         X.X     X.X     X.X     X.X     X.X     X.X       X.X 
                                    Maximum         XX      XX      XX      XX      XX      XX        XX 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Baseline is the last non-missing assessment prior to dosing (Predose), including rechecks and unscheduled 
assessments. 
Programmer Notes: Similar for all time points and ECG parameters. The following time points will be summarized: 
Baseline, Day 1 Hour 2, Day 2, and Day 4. For the change from baseline table 14.3.5.5.2, please remove the baseline 
time point, keep the baseline definition footnote and change the ‘Treatment’ header to ‘Change From Baseline’. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM  
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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Table 14.3.5.5.3 will be in the following format: 
                                                         
 
Table 14.3.5.5.3  12-Lead Electrocardiogram Shift From Baseline (Safety Population) 
 
                                                     Baseline* N               Baseline* ANCS             Baseline* ACS        
                                              -------------------------- -------------------------- -------------------------- 
                                                      Postdose                   Postdose                   Postdose          
                                              -------------------------- -------------------------- -------------------------- 
                       Treatment  Time Point     N       ANCS     ACS       N       ANCS     ACS       N       ANCS     ACS    
                       ------------------------------------------------------------------------------------------------------- 
                           A      Day 1, Hour 2  X        X        X        X        X        X        X        X        X    
                                                                                                                   
                                  Day 2          X        X        X        X        X        X        X        X        X    
                               
 
                                                                                     
 
                           <similar for all time points and treatments> 
 
   
  
  
  
  
  
  
  
  
  
   
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Baseline is the last non-missing assessment prior to dosing (Predose), including rechecks and unscheduled 
assessments. 
N = Normal, ANCS = Abnormal, Not Clinically Significant, ACS = Abnormal, Clinically Significant                                     
                                                
                                                                      
Program:  /CAXXXXX/sas_prg/stsas/tab programname.sas  DDMMMYYYY  HH:MM                                           


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 80 of 105 
11. LISTING SHELLS 
The following listing shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the listings that will be presented and included in the final report. These listings 
will be generated off of the Celerion SDTM Tabulation Model 1.4 mapped in 
accordance with SDTM Implementation Guide 3.2. All listings will be presented in 
Courier New font size 9.  


  
Statistical Analysis Plan                                                                            28 February 2018 
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Page 1 of X 
 
                                   Appendix 16.1.10.1  Clinical Laboratory Reference Ranges  
 
                                                                                           Reference 
        Laboratory Group           Test Name                     Sex         Age Category  Range           Units      
        -------------------------------------------------------------------------------------------------------- 
        Serum Chemistry            Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                                                                                                     
        Hematology                 Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
                                   Test Name                     XXXXXX      XX            XX – XX         units 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<similar for remaining Laboratory Groups and Test Names> 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
                                              
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                          Page 1 of 1 
                                    Appendix 16.2.1  Subject Discontinuation (Safety Population) 
 
                          Subject   Randomized   Study                 Completed 
                 Cohort   Number    Treatment    Period    Date        Study?     Primary Discontinuation Reason 
                 ----------------------------------------------------------------------------------------------- 
                    1        1        A           Post    DDMMMYYYY     YES 
                             2        A           Post    DDMMMYYYY     YES 
                             3      Placebo       Post    DDMMMYYYY     NO       Adverse Event 
 
 
 
 
 
Treatment A: < >  
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
Subjects included in the food effect cohort are listed according to the treatment they were randomized to 
receive in Period 1.  
 
 
Program:  /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_dis.sas  DDMMMYYYY  HH:MM 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                                      Appendix 16.2.4.1  Demographics (Safety Population)  
                                                                                                                                
                                                                                                           Body Mass   Informed 
         Subject    Date Of    Age*                                                      Height   Weight     Index      Consent 
Cohort   Number      Birth     (yrs)   Sex      Race            Ethnicity                 (cm)     (kg)     (kg/m²)      Date 
--------------------------------------------------------------------------------------------------------------------------------- 
   1         X     DDMMMYYYY    XX     Male     < >             Not Hispanic or Latino    XXX      XX.X      XX.XX     DDMMMYYYY 
             X     <similar to above> 
 
 
 
 
 
* Age is derived from birth date to date of first dose. 
 
 
Program:  /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_dem.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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Appendix 16.2.4.2  Physical Examination (Safety Population) 
  
                                                                                                                    
                   Subject  Study                           Was Physical 
           Cohort  Number   Period         Date            Exam Performed?      Comment 
          ---------------------------------------------------------------------------------------------- 
             X       X      Screen       DDMMMYYYY            Yes              XXXXXXXXXXXXXXXXXXXXX         
                     X      Screen       DDMMMYYYY            Yes                
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                                  Appendix 16.2.4.3 Medical and Surgical History (Safety Population) 
   
                       Date 
         Subject    Any     Study                                                    ----------------------                                         
 Cohort  Number   History?  Period  Body System                Category              Start         End          Ongoing?  Condition or Event                 
-------------------------------------------------------------------------------------------------------------------------------------------- 
    X      X        XXX     Screen  XXXXXX  XXXXX               Medical              DDMMMYYYY                    XXXX    XXXXXXX XXXXXX XX                  
                                                                Surgical             DDMMMYYYY    DDMMMYYYY    
           X        XXX     Screen  XXXXXXXX XXXXX              Medical              DDMMMYYYY    DDMMMYYYY            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                                    Appendix 16.2.4.4  Substance Use (Safety Population) 
  
 
 
                                                 
          Subject   Study                                                Start       End                                                     
 Cohort   Number    Period    Substance       Description of Use         Date        Date            
 ------------------------------------------------------------------------------------------ 
   X        X       Screen    XXXXXXXX XXX    XXXXXXXXXX XXXXXX XXXX    DDMMMYYYY   DDMMMYYYY       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                                  Appendix 16.2.5.1.1  Inclusion Criteria  
  
  
   X.  < >.  
   X.  < >.                                  
   X.  < >.                                                                                         
   X.  < >.             
   X.  < >.            
   X.  < >.             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 88 of 105 
 
                                                                                                                                 Page 1 of X 
 
                                                  Appendix 16.2.5.1.2  Exclusion Criteria  
  
  
   X.  < >.  
   X.  < >.                                  
   X.  < >.                                                                                         
   X.  < >.            
   X.  < >.             
   X.  < >.             
   X.  < >.             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                       Page 1 of 1 
                                                   Appendix 16.2.5.2  Subject Eligibility (Safety Population) 
 
                                              Subject  Study          Did subject meet 
                                      Cohort  Number   Period    all eligibility criteria?    Specify 
                                      ---------------------------------------------------------------------------- 
                                         X         X   Screen               YES 
 
                                                   X   Screen               YES 
            <This column is 
                                                                                               only presented if 
                                                                                               data are present.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
Appendix 16.2.5.3.1  Check-in and Return Criteria  
  
  
    
   X.  Did the Subject report any study restriction violations since the last study visit?                                             
   X.  IF YES TO ANY QUESTION, WAS SUBJECT APPROVED FOR STUDY?                                                                             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                              Page 1 of X 
 
Appendix 16.2.5.3.2  Check-in and Return Responses (Safety Population) 
  
 
                                                              Check-in Criteria 
         Subject  Study                                       ------------------                                                          
 Cohort  Number   Period   Day   Hour  Date       Time           1          2       Specify                                                 
----------------------------------------------------------------------------------------------------------------------------------------- 
    X      X        X      -X   -XX.X  DDMMMYYYY  HH:MM          No         NA     Will only be present and populated if there is a comment                  
           X        X      -X   -XX.X  DDMMMYYYY  HH:MM          No         NA       present in the study database.                                          
           X        X      -X   -XX.X  DDMMMYYYY  HH:MM          No         NA                                                            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
           
                                             
Please refer to Appendix 16.2.5.3.1 for the Check-in criteria. 
NA = Not applicable  
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
                                                                 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 92 of 105 
 
                                                                                                                                 Page 1 of X 
 
                                        Appendix 16.2.5.4.1  Test Compound Description (Safety Population) 
  
                         Compound                                         Form             Route    
                         -------------------------------------------------------------------------- 
                         XXXXXXXXXXXXXX                                    < >             XXXX     
 
                         XXXXXXXXXXXXXX                                    < >             XXXX     
                                                                                                                                                 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                          Appendix 16.2.5.4.2  Test Compound Administration Times (Safety Population)  
  
                                                           Start 
          Subject   Study                            -------------------                                                                               
 Cohort   Number    Period  Treatment  Day   Hour    Date        Time     Compound              Dosage    Comments                
------------------------------------------------------------------------------------------------------------------------------ 
   X        X        X         X        X    X.XX    DDMMMYYYY   X:XX:XX  XXXXXXXXX              < >      XXXXXXXXXXXXXXXXXXX                     
            X        X         X        X    X.XX    DDMMMYYYY   X:XX:XX  XXXXXXXXX              < >       
            X        X         X        X    X.XX    DDMMMYYYY   X:XX:XX  XXXXXXXXX              < >       
  
                                                                                                      
 
  
 
 
 
 
 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                       Page 1 of X 
                       Appendix 16.2.5.5  Blood Draw Times (Safety Population) 
 
         Subject   Study                                            Actual 
Cohort   Number    Period   Treatment   Day    Hour      Date        Time     Bioassay   Comments 
-------------------------------------------------------------------------------------------------- 
   1        1      1            A        X     -X.XX   DDMMMYYYY   HH:MM:SS   XXXXXXXX 
                                         X     XX.XX   DDMMMYYYY   HH:MM:SS   XXXXXXXX 
                                         X     XX.XX   DDMMMYYYY   HH:MM:SS   XXXXXXXX 
                                         X     XX.XX   DDMMMYYYY   HH:MM:SS   XXXXXXXX 
                                         X     XX.XX   DDMMMYYYY   HH:MM:SS   XXXXXXXX 
                                <similar for all other time points and subjects> 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                       Page 1 of X 
                               Appendix 16.2.5.1.6  Urine Collection Times - SAD (Safety Population) 
 
                                                                        Urine Collection 
                                                            ----------------------------------------- 
                                                                            Start                 Stop 
           Subject  Study              Collection     Collection     -------------------   -------------------   Weight 
  Cohort   Number   Period  Treatment   End Day        Interval        Date       Time       Date       Time     (unit)  Comments 
  ----------------------------------------------------------------------------------------------------------------------------------------- 
     X        X      X         X             1          -X.XX        DDMONYYYY  HH:MM:SS   DDMONYYYY  HH:MM:SS    XXX 
                                                         -.XX        DDMONYYYY  HH:MM:SS   DDMONYYYY  HH:MM:SS           SAMPLE PROCESSING 
                                                                                                                         NOT REQUIRED 
                                                     -X.XX - X.XX    <similar to above for all time points and subjects> 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                                 Page 1 of X 
 
                                          Appendix 16.2.5.7  Meal Times (Safety Population) 
  
         Subject  Study                            Timed Interval                 Actual       Start     Stop                                                
 Cohort  Number   Period Treatment    Day  Hour  (Start HR to Stop HR)  Event      Date         Time      Time        Comments                               
 -------------------------------------------------------------------------------------------------------------------------------- 
   X        X       X      X          -X  -XX.XX                       DINNER     DDMMMYYYY   XX:XX:XX  XX:XX:XX                                             
                                          -XX.XX                       SNACK      DDMMMYYYY   XX:XX:XX  XX:XX:XX 
                                       X   -X.XX    -X.X TO –X.XX      BREAKFAST  DDMMMYYYY   XX:XX:XX  XX:XX:XX                                             
                                           XX.XX                       LUNCH      DDMMMYYYY   XX:XX:XX  XX:XX:XX                                             
                                           XX.XX                       DINNER     DDMMMYYYY   XX:XX:XX  XX:XX:XX                                             
                                           XX.XX                       SNACK      DDMMMYYYY   XX:XX:XX  XX:XX:XX                                             
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
HR = Hour 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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Page 1 of 1 
                     Appendix 16.2.5.8  Prior and Concomitant Medications (Safety Population) 
 
                                                                                                                                     Prior  
        Subject  Any   Treat- Medication                           Start   Start   Stop      Stop                                    to     
Cohort  Number   Med?   ment  (WHO DD*)     Dosage    Route        Date    Time    Date      Time  Frequency Indication Continuing?  Study? 
-------------------------------------------------------------------------------------------------------------------------------------------- 
   1       1     NO          None                                                                                                            
                                                                                                                                            
           2     NO          None                                                                                                            
                                                                                                                                            
           3     YES         CETIRIZINE     X MG    BY MOUTH    DDMMMYYYY    UNK  DDMMMYYYY HH:MM XXXXXXX     XXXXXXX   NO          Yes    
                             (CETIRIZINE)                                                                                                    
                         X   PARACETAMOL    X MG    XXXXXXXXX   DDMMMYYYY  HH:MM  DDMMMYYYY HH:MM XXXXXXXX    XXXXXXXX  XX        
                             (PARACETAMOL) 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
*Concomitant medications are coded with WHO Dictionary Version 01Mar2017.                                                             
Med = Medication, UNK = Unknown, WHO DD = World Health Organization Drug Dictionary 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
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                                                                                                                       Page 1 of X 
                    Appendix 16.2.7.1.1  Adverse Events (I of II) (Safety Population) 
 
                                                                                Time From 
                                                                                Last Dose        Onset           Resolved         Duration 
         Subject                                                               -----------   ---------------   ---------------   ---------- 
Cohort   Number    Treatment   TE?  Adverse Event       Preferred Term*         (DD:HH:MM)    Date    Time      Date    Time     (DD:HH:MM) 
------------------------------------------------------------------------------------------------------------------------------------------- 
   1        1                       None 
 
            2                       None 
 
            3                  No   XXXXXXXXXXXXX       XXXXXXXXXXXXXXXXX        DD:HH:MM   DDMMMYYYY HH:MM   DDMMMYYYY HH:MM     DD:HH:MM 
                                    XXXXXXXXXXXXXXXXX   XXXXXXXXXXXX 
                       X       Yes  XXXXXXXXXXXXXXXXX   XXXXXXXXXXXXXXXXXXXXXX   <similar to above> 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
* Adverse events are coded using MedDRA Version 20.0. 
TE = Treatment-emergent 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 99 of 105 
                                                                                                                       Page 1 of 1 
                    Appendix 16.2.7.1.2  Adverse Events (II of II) (Safety Population) 
 
                                                                                                                  Relation- 
                                                                Onset                                             ship to 
         Subject                                           ---------------           Severity                     Study 
Cohort   Number    Treatment   Adverse Event                 Date    Time    Freq^    Grade*    Ser**  Outcome    Drug          Action 
--------------------------------------------------------------------------------------------------------------------------------------- 
   1        1                  None 
 
            2                  None 
 
            3                  XXXXXXXXXXXXXXXXXXXXX       DDMMMYYYY HH:MM   Cont.      1      NS     Resolved   Unrelated   None 
                       X       XXXXXXXXXXXXXXXXXXXXX       DDMMMYYYY HH:MM   <similar to above> 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
^ Freq represents Frequency:  SE = Single Episode, Inter. = Intermittent, Cont. = Continuous 
* Ser represents Serious:  NS = Not Serious 
** Severity Grade: 1 = Mild, 2 = Moderate, 3 = Severe or medically significant but not immediately life-threatening,  
4 = Life-threatening consequences   
 
 
Program:  /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_ae2.sas  DDMMMYYYY  HH:MM  
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 100 of 105 
                                                                                                                       Page 1 of 1 
                  Appendix 16.2.7.2  Adverse Event Non-Drug Therapy (Safety Population) 
 
                                                                 Onset              Procedure Given 
         Subject                                            ---------------   -------------------------------- 
Cohort   Number    Treatment   Adverse Event                  Date    Time      Date    Time    Description 
-------------------------------------------------------------------------------------------------------------- 
   X        X         X        < >                          DDMMMYYYY HH:MM   DDMMMYYYY HH:MM   TRENDELENBURG        
                                                                                                POSITION 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_dev/cdash_lis_ae3.sas  DDMMMYYYY  HH:MM                                                                 
 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 101 of 105 
                                                                                                                     Page 1 of 1 
                  Appendix 16.2.7.3  Adverse Event Preferred Term Classification (Safety Population) 
 
                                                                                                                               Onset 
         Subject                                                                                                         ---------------- 
Cohort   Number    Treatment   Adverse Event                Preferred Term*                System Organ Class              Date     Time 
----------------------------------------------------------------------------------------------------------------------------------------- 
   1        1                  None 
 
            2                  None 
 
            3          X       XXXXXXXXXXXXXXXX             XXXXXXXXXXXXXXXXXXXXXX         XXXXXXXXXXXXXXXXXXXXX         DDMMMYYYY  HH:MM 
                               XXXXXXXXXXXXXXXXXXXXXXXX     XXXXXXXXXXXXXXXXXXXXXX         XXXXXXXXXXXXXXXXXXXXXXXXX     DDMMMYYYY  HH:MM 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
 * Adverse events are coded using MedDRA Version 20.0. 
 
 
Program:  /CAXXXXX/sas_prg/stsas/standardlis/cdash_lis_ae4.sas  DDMMMYYYY  HH:MM 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 102 of 105 
 Appendices 16.2.8.1.1 – 16.2.8.1.4 will be in the following format:      
                                                                                                                             Page 1 of X 
 
                                   Appendix 16.2.8.1.1  Clinical Laboratory Report - Serum Chemistry (Safety Population)  
  
                                                                                                                                                
                                                                    Parameter1  Parameter2   Parameter3    Parameter4  Parameter5 Parameter6  
          Subject   Age#/  Study   Treat-                             < Range>    < Range>     < Range>      < Range>    < Range>   < Range>                 
  Cohort  Number    Sex    Period  ment   Day   Hour   Date      Time  (Unit)      (Unit)       (Unit)        (Unit)      (Unit)     (Unit)      
  ------------------------------------------------------------------------------------------------------------------------------------------ 
    X        X      XX     Screen          .           DDMMMYYYY HH:MM:SS   XX HN       XX           XX            XX          XX HN      XX        
                             X       X    -X   -XX.X   DDMMMYYYY HH:MM:SS   XX LYR+     XX LN        XX            XX LY-      XX         XX        
 
 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
# Age is calculated at the time of first dosing. F = Female, M = Male 
H = Above reference range, L = Below reference range                                                                     
Computer: N = Not clinically significant, Y = Clinically significant                                                           
PI Interpretation: - = Not clinically significant, R = Recheck requested, ^ = Will be retested later, + = Clinically significant 
          
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
Programmer Notes:  Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early term chronologically 
with other scheduled assessments and rechecks.  Recheck should be sorted with the scheduled time point the recheck is 
for. Serum Cortisol results will be presented in a separate listing (16.2.8.1.2).  
Clinically significant lab values generally will be captured as AEs, some of which the PI may indicate in Appendix 
16.2.8.1.6 lab comments (as per GPG.03.0028 sections 2.9 and 2.10). Derive an additional flag for PI flag (+) based on 
positive CS/Clinically Significant comments. Present this derived 4th column in all tables, and list only PI-determined 
out-of-range clinically significant lab values in Table 14.3.4.5. 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 103 of 105 
                                                                                                                                 Page 1 of X 
 
                                         Appendix 16.2.8.1.5  Clinical Laboratory Report – Comments (Safety Population) 
  
        Subject Age#/ Study                                                                                                                             
 Cohort Number  Sex   Period  Treatment  Day  Hour   Date       Department      Test            Result       Unit      Comment                     
 --------------------------------------------------------------------------------------------------------------------------------------- 
   X     X       X     X       X       -X  -XX.X    DDMMMYYYY  Other Tests     Fibrinogen      XXX          mg/dL     Not significant in the      
                                                                                                                      context of this study.      
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
# Age is calculated at the time of first dosing. F = Female, M = Male 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 104 of 105 
                                                                                                                                Page 1 of X 
 
                                                      Appendix 16.2.8.2  Vital Signs (Safety Population)  
  
  
   Blood Pressure 
                                                                        (mmHg)                Respi-   Tempera-                       
         Subject  Study                                            -----------------  Pulse   ration   ture      Weight           
  Cohort Number   Period  Treatment Day  Hour     Date       Time    Test  Sys/Dia    (bpm)   (rpm)    (°C)       (kg)     Comment    
 ------------------------------------------------------------------------------------------------------------------------------------------- 
     X      X      Screen             .     .      DDMMMYYYY  X:XX:XX SITX  XXX/ XX    XX     XX      XX         XXX.X    
                     X        X      -X  -XX.X     DDMMMYYYY  X:XX:XX SITX  XXX/ XX    XX                        XXX.X 
                                      X   XX.X     DDMMMYYYY  X:XX:XX SITX             XX                             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
SITX = X-minute sitting, Sys = Systolic, Dia = Diastolic, R = Recheck value  
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


  
Statistical Analysis Plan                                                                            28 February 2018 
Page 105 of 105 
 
                                                                                                                      Page 1 of 1 
                                 Appendix 16.2.8.3  12-Lead Electrocardiogram (Safety Population) 
 
                                                                             Heart 
         Subject   Study    Treat-                                            Rate    PR    QRS    QT    QTcF* 
Cohort   Number    Period   ment    Day   Hour     Date      Time   Result   (bpm)  (msec) (msec) (msec) (msec)   Comments 
-------------------------------------------------------------------------------------------------------------------------------------------- 
   X        1      Screen                        DDMMMYYYY HH:MM:SS ANCS      XX     XXX     XX    XXX    XXX     EARLY REPOLARIZATION; LEFT 
                                                                                                                  AXIS DEVIATION 
                   1          X     -X   -XX.XX  DDMMMYYYY HH:MM:SS ANCS      XX     XXX     XX    XXX    410     LEFT AXIS DEVIATION 
                                     X     X.XX  DDMMMYYYY HH:MM:SS 
                                     X    XX.XX  DDMMMYYYY HH:MM:SS < >       XX     XXX     XX    XXX    441 @   SINUS BRADYCARDIA 
                                     X     X.XX  DDMMMYYYY HH:MM:SS < >       XX     XXX     XX    XXX    451#@ 
                                     X    XX.XX  DDMMMYYYY HH:MM:SS < >       XX     XXX     XX    XXX    XXX 
 
 
 
 
 
Treatment A: < > 
Treatment B: < > 
Treatment C: < > 
Treatment D: < > 
Treatment E: < > 
Treatment F: < > 
Treatment G: < > 
Treatment Placebo: < > 
ANCS = Abnormal, Not Clinically Significant, ACS = Abnormal, Clinically Significant 
QTcF* = QT corrected for heart rate using Fridericia's correction. 
# = QTcF > 450, @ = QTcF change from baseline greater than 30 msec 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM