A Phase 1a, Randomized, Double-Blind, Placebo-Controlled, Single Center Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CS-1103 Following Single, Ascending Intravenous Dose Administration in Healthy Participants
Phase: PHASE1
Conditions: Substance Use Disorders, Methamphetamine Abuse, Methamphetamine Intoxication
Sponsor: Clear Scientific, Inc.

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TITLE PAGE 
Protocol Title: A Phase 1a, Randomized, Double-Blind, Placebo-Controlled, Single Center Study to Evaluate 
the Safety, Tolerability, and Pharmacokinetics of CS-1103 Following Single, Ascending 
Intravenous Dose Administration in Healthy Participants 
Protocol Number: CS-1103-01 
Amendment Number: 2 
Compound: CS-1103 Concentrate for Solution for Infusion  
Brief Title: A Phase 1a Safety, Tolerability and PK Study of CS-1103 in Healthy Participants 
Indication: To lower the level of methamphetamine in the human body 
Study Phase: 1a 
Sponsor Name: Clear Scientific, Inc. 
Legal Registered Address: 
 
Regulatory Agency Identifier Number(s): 
 
Original Protocol Version and Date: Version 1.0, 01 June 2023 
Protocol Amendment 1 Version and Date: Version 2.0 Amendment 1, 25 September 2023 
Protocol Amendment 2 Version and Date: Version 3.0 Amendment 2, 03 October 2023 

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Approval Date: 03 October 2023
Medical Monitor name and contact information will be provided separately.  

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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Table 1 
Document History 
Document 
Date 
Substantial 
Region 
Amendment 2 
02-Oct-2023 
No 
Global 
Amendment 1 
25-Sep-2023 
Yes 
Global 
Original Protocol 
01-Jun-2023 
- 
- 

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TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1 
Synopsis .......................................................................................................... 13 
1.2 
Schema ............................................................................................................ 16 
1.3 
Schedule of Activities .................................................................................... 17 
2.0 
INTRODUCTION ..................................................................................................... 21 
2.1 
Study Rationale .............................................................................................. 21 
2.2 
Background .................................................................................................... 21 
 
 
2.3 
Benefit/Risk Assessment................................................................................ 23 
3.0 
OBJECTIVES AND ENDPOINTS .......................................................................... 24 
4.0 
STUDY DESIGN ....................................................................................................... 25 
4.1 
Overall Design ................................................................................................ 25 
4.2 
Scientific Rationale for Study Design .......................................................... 26 
4.3 
Justification for Dose ..................................................................................... 26 
4.4 
End of Study Definition ................................................................................. 28 
4.5 
Dose Escalation .............................................................................................. 28 
4.6 
Study Stopping Criteria ................................................................................ 29 
4.6.1 
Criteria for Stopping Dose Escalation ............................................... 29 
4.6.2 
Criteria for Stopping the Study ......................................................... 29 
5.0 
STUDY POPULATION ............................................................................................ 30 
5.1 
Inclusion Criteria ........................................................................................... 30 
5.2 
Exclusion Criteria .......................................................................................... 31 
5.3 
Lifestyle Considerations ................................................................................ 32 
5.3.1 
Meals and Dietary Restrictions ......................................................... 32 
5.3.2 
Caffeine, Alcohol, and Tobacco ........................................................ 33 
5.3.3 
Activity .............................................................................................. 33 
5.4 
Screen Failures ............................................................................................... 34 
5.5 
Criteria for Temporarily Delaying Enrollment/Randomization .............. 34 
6.0 
STUDY TREATMENT(S) AND CONCOMITANT THERAPY ......................... 35 
6.1 
Study Treatments Administered .................................................................. 35 
6.2 
Preparation, Handling, Storage, and Accountability ................................. 36 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................... 37 
6.4 
Study Treatment Compliance ...................................................................... 37 
6.4.1 
Study Treatment Strategy .................................................................. 38 
6.4.2 
Individual Study Treatment Adjustment/Interruption ....................... 38 
6.5 
Dose Modification .......................................................................................... 38 
6.6 
Concomitant Therapy ................................................................................... 38 

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6.7 
Monitoring and Management of Hypersensitivity Reactions .................... 39 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 40 
7.1 
Discontinuation of Study Treatment............................................................ 40 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................... 40 
7.3 
Lost to Follow-up ........................................................................................... 41 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 42 
8.1 
Efficacy Assessments ..................................................................................... 42 
8.2 
Safety Assessments ........................................................................................ 42 
8.2.1
Physical Examinations ...................................................................... 43
8.2.2 
Vital Signs ......................................................................................... 43 
8.2.3 
Electrocardiograms ........................................................................... 44 
8.2.4 
Anxiety Symptoms Questionnaire .................................................... 45 
8.2.5 
Clinical Safety Laboratory Tests ....................................................... 45 
8.2.6 
Pregnancy Testing ............................................................................. 46 
8.2.7 
Medical History/Demographics ........................................................ 46 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 46 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................ 47 
8.3.2 
Method of Detecting AEs and SAEs ................................................. 47 
8.3.3 
Follow-up of AEs and SAEs ............................................................. 47 
8.3.4 
Regulatory Reporting Requirements for SAEs ................................. 48 
8.3.5 
Pregnancy .......................................................................................... 48 
8.4 
Pharmacokinetics .......................................................................................... 49 
8.4.1 
Collection of Samples ....................................................................... 49 
8.4.2 
Determination of Drug Concentration .............................................. 50 
8.4.3 
Calculation of Derivation of Pharmacokinetic Variables ................. 50 
8.5 
Pharmacodynamics ....................................................................................... 51 
8.6 
Genetics .......................................................................................................... 52 
8.7 
Biomarkers ..................................................................................................... 52 
8.8 
Immunogenicity Assessments ....................................................................... 52 
8.9 
Health Economics .......................................................................................... 52 
9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 53 
9.1 
Statistical Hypotheses .................................................................................... 53 
9.2 
Analysis Sets ................................................................................................... 53 
9.3 
Statistical Analyses ........................................................................................ 53 
9.3.1 
General Considerations ..................................................................... 53 
9.3.2 
Pharmacokinetic Analyses ................................................................ 54 
9.3.3 
Safety Analyses ................................................................................. 54 
9.4 
Interim Analysis ............................................................................................. 55 
9.5 
Sample Size Determination ........................................................................... 55 

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10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 56 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 56 
10.1.1 
Regulatory and Ethical Considerations ............................................. 56 
10.1.2 
Adequate Resources .......................................................................... 57 
10.1.3 
Financial Disclosure .......................................................................... 57 
10.1.4 
Insurance ........................................................................................... 57 
10.1.5 
Informed Consent Process................................................................. 57 
10.1.6 
Data Protection .................................................................................. 57 
10.1.7 
Committees Structure ........................................................................ 58 
10.1.8 
Dissemination of Clinical Study Data ............................................... 59 
10.1.9 
Data Quality Assurance ..................................................................... 59 
10.1.10 Source Documents ............................................................................ 60 
10.1.11 Study and Site Start and Closure ....................................................... 60 
10.1.12 Publication Policy ............................................................................. 61 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 63 
10.3 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Treatment ....................................................................................................... 65 
10.3.1 
Definition of AE ................................................................................ 65 
10.3.2 
Definition of SAE ............................................................................. 66 
10.3.3 
Reporting of SAEs ............................................................................ 68 
10.4 
Appendix 4: Contraceptive and Barrier Guidance and 
Collection of Pregnancy Information .......................................................... 70 
10.4.1 
Definitions ......................................................................................... 70 
10.4.2 
Contraception Guidance .................................................................... 70 
10.5 
Appendix 5: Abbreviations ........................................................................... 73 
11.0 
REFERENCES .......................................................................................................... 76 
 

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LIST OF TABLES 
Table 1 
Schedule of Activities ....................................................................................... 17 
Table 2 
Detailed Schedule of PK, Urine, dECG, Safety ECG, ASQ, Injection Site 
Assessment and Vital Signs During Single IV 
 .................. 19 
Table 3 
Study Treatments Administered ....................................................................... 35 
Table 4 
Plasma Pharmacokinetic Parameters ................................................................ 50 
Table 5 
Urine Pharmacokinetic Parameters .................................................................. 51 
Table 6 
Protocol-required Laboratory Tests .................................................................. 63 
 
LIST OF FIGURES 
Figure 1 
Study Schema .................................................................................................. 16 
 

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Exploratory 
 
 
To explore the relationship between CS-1103 
plasma concentrations and changes in QT 
intervals during dosing, if any 
 
Concentration-QT correlation performed on 
baseline-corrected QTcF time-matched with PK. 
Concentration-QT correlation may be reported 
separately from the clinical study report 
Abbreviations: AE = adverse event; Ae = amount; AUC = area under the concentration versus time curve; 
AUC(0-inf) = AUC from time zero extrapolated to infinity; AUC(0-last) = AUC from time zero to the last 
quantifiable concentration; CEOI = concentration at the end of 10-minute IV infusion; CL = systematic 
clearance; CLr = renal clearance; Cmax = maximum concentration; ECG = electrocardiogram; fe = fraction; 
IV = intravenous; z = elimination rate constant; PK = pharmacokinetics; t1/2 = half-life; QTcF = QT corrected 
for heart rate by Fridericia’s formula; tmax = time to Cmax; Vss = volume of distribution at steady-state following 
intravenous dosing; Vz = volume of distribution following intravenous dosing. 
 
Overall Design: 
CS-1103-01 is a Phase 1a, single center, double-blind, placebo-controlled, randomized, single 
ascending-dose first in-human (FIH) study. All participants will be screened within 28 days of 
dose administration and participants will check-in to the inpatient clinical research unit (CRU) 
on their Admission/
1. Participants will be randomized on 
1, the day prior to 
dosing, after meeting all eligibility criteria. Participants are scheduled to remain in the CRU 
for up to 48 hours postdose for safety and PK assessments. 
Number of Participants: 
Up to 40 healthy participants, aged 18 to 55 years will be randomized. 
Intervention Cohorts and Duration: 
Up to 5 cohorts of 8 participants (6 active, 2 placebo participants per cohort) will be enrolled 
with each participant assigned to receive a single dose of CS-1103 or placebo on 1 occasion 
(Day 1). Note: The dose will be capped at 3000 mg. 
 Cohort 1: Dose level 1 (CS-1103 2.7 mg/kg, 
) or placebo (
) 
 Cohort 2: Dose level 2 (CS-1103 8.0 mg/kg, 
) or placebo (
) 
 Cohort 3: Dose level 3 (CS-1103 16.0 mg/kg, 
) or placebo (
) 
 Cohort 4: Dose level 4 (CS-1103 26.7 mg/kg, 
) or placebo (
) 
 Cohort 5: Dose level 5 (CS-1103 40.0 mg/kg, 
) or placebo (
) 
The study duration will be approximately 37 days. 
 Screening Period: up to 28 days 
 CRU confinement period: 4 days 
o Treatment administration: 1 day 
 CRU discharge through follow-up/end of study period: 5 days 
Statistical Methods: 
Descriptive statistics will be used as applicable to summarize the study data unless otherwise 
specified. Continuous variables: Sample size (n), mean, standard deviation (SD), median, 

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minimum (min), and maximum (max). Summaries for plasma CS-1103 concentrations will 
include the coefficient of variation and PK parameter summaries will also include the 
geometric mean (except for tmax, which will only be presented as min, median, max). 
Categorical variables: Frequencies and percentages. Individual participant data will be 
presented in listings. 
The sample size for this study is based upon precedent set by other Phase 1 studies to gain 
preliminary measure of safety and CS-1103 PK characteristics in a healthy participant 
population and not on statistical considerations of power while exposing as few participants as 
possible to the study treatment and procedures. A sample size of 8 participants per dose level 
(6 active: 2 placebo) in this study design is expected to be sufficient to meet the objectives of 
this study. 
Safety: 
Analysis of safety data will be performed for all participants receiving at least one dose of 
study treatment (CS-1103 or placebo). The frequency of all treatment emergent adverse events 
(TEAEs), TEAEs by maximum severity, TEAEs by relationship to study treatment, serious 
adverse events (SAEs), TEAEs leading to death, and TEAEs leading to discontinuation of 
study treatment will be tabulated by Preferred Term (PT) and System Organ Class (SOC) for 
each treatment cohort. Summary statistics, including change from baseline, for vital signs, 
laboratory parameters, and electrocardiograms (ECGs) intervals will be provided by 
treatment, visit, and time point, as appropriate. For ECG results, appropriate outlier 
tabulations for QT and QT corrected for heart rate by Fridericia’s formula (QTcF) will also be 
presented by treatment. Results of the physical examinations and the Anxiety Symptoms 
Questionnaire (AQS) will be listed and if appropriate, summarized by treatment. 
Pharmacokinetics: 
Analysis of PK data will be performed for all participants receiving at least one dose of 
CS-1103 and have at least 1 quantifiable postdose concentration, without protocol deviations 
or events expected to affect PK results. CS-1103 concentrations and calculated PK parameters 
will be listed and descriptively summarized by treatment and scheduled time point, as 
applicable. Arithmetic mean ±SD and individual CS-1103 plasma concentration versus time 
curves will be plotted on linear and semilogarithmic scale and percent of dose recovered in 
urine over time will be presented graphically, as appropriate. Dose proportionality will be 
explored graphically and by using a power model, as appropriate.  
Data Monitoring/Other Committee: Yes  
Dose escalation, and other decisions related to safety and PK will be made by the Sponsor in 
consultation with a Safety Review Committee (SRC). 
 

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1.2 
Schema 
Figure 1 
Study Schema 
Confinement period
 
 
 
 
 
 
Screening 
 
Admission to 
CRU and 
Randomization 
Dosing 
Discharge 
from CRU 
  
Follow-up  
(EOS) 
 
 
Screening 
period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Days 
8 
to 
 
 
1 
Day 1 
(Single IV dose) 
Day 3 
  
Day 8 (±1 day) 
Abbreviations: CRU = clinical research unit; EOS = end of study, IV = intravenous.
Up to 40 participants randomized to 5 cohorts of 8 participants each (6 active, 2 placebo participants per cohort). 
Note: Admission/Day 1 may span 2 days in the CRU, in that case screening will end on 
3 for participants 
with Admission Day spanning 2 days in the CRU. 

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a. 
All participants within a given cohort may check-in on the day prior to sentinel dosing and remain 
confined to the study center until their discharge day. Two participants will be randomized for dosing in 
the sentinel group, and the remaining participants may be eligible to participate in the main cohort group 
without repeating the admission evaluations, provided they were in confinement the entire time. The 
remaining participants will have a set of vital signs and AE/concomitant medication review performed 
on the day prior to their dosing day. For remaining participants, Admission/Day 1 may span 2 days in 
the CRU. Note: Screening may end on Day 3 for participants with Admission Day spanning 2 days in 
the CRU. 
b. 
Participants who discontinue from the study prematurely should perform the Follow-up/EOS Visit as 
soon as possible after discontinuation. 
c. 
A COVID-19 test will be performed at Admission and for which a negative result must be available 
prior to study treatment administration.  
d. 
Includes over-the-counter medications, herbal medications/supplements, and other supplements. 
e. 
Clinical laboratory tests: hematology, clinical chemistry (including liver and renal function), 
coagulation, and urinalysis with microscopic examination to be performed at screening, on 
Admission/Day 1, Day 2 and EOS. In addition, urinalysis will be performed for each urine sample 
collected on Day 1. Protocol-required laboratory tests are detailed in Section 10.2, Table 6. 
f. 
Triplicate 12-lead ECGs will be obtained following at least 5 minutes remaining in a supine position and 
collected before other simultaneously scheduled procedures, i.e., vital signs and blood collections. 
Single ECGs may be collected during the first 30 minutes post-EOI to allow completion of all 
simultaneously scheduled procedures (see Table 2). 
g. 
On Admission/Day 1, continuous Holter Monitoring will be performed for 4 hours. If needed, any 
repeat ECG needs to be performed in triplicate. 
h. 
On Day 1, continuous Holter Monitoring will commence approximately 1 hour prior to study treatment 
administration and continue through 24 hours postdose. The ECGs will be extracted from Holter to be 
time-matched with PK samples (see Table 2).  
i. 
Vital signs (Systolic, diastolic, and mean blood pressure, pulse rate, respiratory rate, oxygen saturation, 
and body temperature) will be measured following at least 5 minutes remaining in a supine position 
following ECG collection (see Table 2 and Section 8.2.2 for details). If needed, repeat vital signs may 
be performed.  
j. 
Complete physical examination at screening and at end of study. Brief physical examination on 
Admission/Day 1 at check-in, Day 2, and Day 3. 
k. 
On Day 1, the injection site will be evaluated prior to study treatment administration and again 
immediately after study treatment administration, in approximately (+15 minutes) hourly intervals for 
up to 6 hours postdose. Injection site assessment also occurs any time on Day 2, and any time prior to 
discharge from the CRU on Day 3. (see Section 8.2.1.1 for details on the 4-point scale injection site 
assessment). 
l. 
On Day 1, ASQ will be completed predose (within 60 minutes prior to dosing) and approximately 10 
minutes (+15 minutes), 1 hour (+15 minutes), and 2 hours (+15 minutes) postdose. This assessment will 
be performed after completion of all other simultaneously scheduled procedures to avoid interference 
with scheduled vital sign, ECG, and PK evaluation (see Section 8.2.4). 
m. 
All SAEs will be collected from the signing of the ICF until the last study visit at the timepoints 
specified in the SoA. All AEs will be collected from the start of study treatment until the last study visit 
at the timepoints specified in the SoA. 
n. 
Study Treatment will be administered on Day 1 in the morning after at least a 10 hour overnight fast 
with an approximately 4 hour fast following dose administration. Note: All scheduled postdose 
assessments listed in Table 1 and Table 2 are relative to the start of the IV infusion. 
o. 
PK blood and urine collection timepoints (see Table 2). 
 

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Abbreviations: ASQ: Anxiety Symptoms Questionnaire; CRU = clinical research unit; dECG: Digital 
electrocardiogram; EOI = end of infusion; hr = hour; IV = intravenous; min = minutes; PK: pharmacokinetics; 
(T=0) = Time equals 0. 
 
* Continuous Holter performed during the day of admission  
a. 
All predose procedures and PK blood samples may be taken up to 60 minutes prior to start of the 
10 minute IV infusion on Day 1. All postdose procedures and PK blood samples will be collected 
relative to the end of the IV infusion unless otherwise indicated or there is a significant extension of the 
infusion duration (see footnote b below). 
b. 
The following windows will be allowable for PK samples: a ±1 minute window will be allowed for 
samples taken up to and including 10 minutes postdose, a ±2 minute window will be allowed for 
samples at 20 and 30 minutes postdose, a ±4 minute window will be allowed for samples at 40 minutes, 
50 minutes, and 1 hour postdose, a ±10 minute window for samples taken between 1.5 hours and 3 
hours postdose; a ±15 minute window is acceptable for samples taken at >3 hours postdose, and a ±30 
minute window is acceptable for samples taken at >12 hours postdose.  
c. 
A small amount of urine will be removed at each interval for urinalysis. Removal of urine will occur 
after the volume of the pooled urine has been recorded. 
d. 
ECGs to be extracted from the continuous Holter on Days 1 and 2 as listed in Table 2 and will be 
time-matched with PK sample collections from predose to 24-hour postdose. Digital ECG assessments 
will be extracted at a time prior to the PK sample collection. Participants will remain in supine position 
for at least 5 minutes before each of the planned ECG extraction. 
e. 
Scheduled safety ECG by site for in-time evaluation of ECGs. Timepoints will be from the start of the 
triplicate assessment as indicated. Single ECG will be collected at the 10 and 30 minutes post EOI 
timepoints.  
f. 
Vital signs can be taken any tim
 
g. 
On Day 1, ASQ will be completed predose (within 60 minutes prior to dosing) and approximately 10 
minutes (+15 minutes), 1 hour (+15 minutes), and 2 hours (+15 minutes) postdose. This assessment will 
be performed after completion of all other simultaneously scheduled procedures to avoid interference 
with scheduled vital sign, ECG, and PK evaluation (see Section 8.2.4). 
h. 
On Day 1, the injection site will be evaluated prior to study treatment administration and again 
immediately after study treatment administration, in approximately hourly (+15 minutes) intervals for 
up to 6 hours postdose. Injection site assessment also occurs any time on Day 2, and any time prior to 
discharge from the CRU on Day 3 (see Section 8.2.1.1 for details on the 4 point scale injection site 
assessment). 
i. 
If the duration of the short 10 minute infusion exceeds 15 minutes, or an interruption occurs that 
exceeds the duration of infusion to more than 15 minutes, for PK blood collection (postdose) up and 
including 3 hours, every effort should be made to follow the time relative to the end of infusion. 
j. 
Blood pressure measurements for 5 minutes post start of infusion, at EOI, and 20 minute post EOI 
timepoints will be single readings.  
 
 
The timing of PK (both plasma and urine), safety ECG, and vital sign assessments may be adjusted based on 
emerging data. Furthermore, in case that CS-1103 half-life is less than 4 hours, Holter recording may be 
discontinued at a time earlier than 24 hours post IV infusion. Furthermore, up to 2 additional blood collections 
may be added on Day 1, Day 2, or Day 3; pooled urine collections may be extended, and discharge may be 
delayed for up to 8 hours to optimize PK assessment without preparation of an amendment.

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2.0 INTRODUCTION 
2.1 
Study Rationale 
The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of 
single, ascending doses of CS-1103, administered by intravenous (IV) infusion in healthy 
participants. 
2.2 
Background 
There is an urgent need for a rapidly acting reversal agent for methamphetamine (meth) 
intoxication. Meth is the fastest growing drug of abuse in the U.S., representing nearly 
800,000 annual emergency room visits,1 with deaths increasing 14-fold since 2015 
(32,856 deaths in 2021 alone),2,3 yet no current therapeutics are available for treating meth 
intoxication. 
Clear Scientific is developing CS-1103 to treat acute toxic effects of meth. CS-1103 lowers 
the level of meth in the body by sequestering it in the central compartment, and accelerating 
its renal clearance into urine, therefore mitigating its toxic effects. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clear Scientific has completed a nonclinical program in compliance with guidelines published 
by the Food and Drug Administration (FDA).10 The results are summarized in the current 
Investigator’s Brochure (IB).  
 
 
 
 
 
  
 
 
 
The purpose of the planned Phase 1a clinical trial is to evaluate the safety, tolerability, and PK 
of CS-1103 following a single, ascending IV dose administration in healthy participants. The 
proposed route of administration in humans is IV. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 

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2.3 
Benefit/Risk Assessment 
The benefit of the present study is that it will provide important human data on the safety, 
tolerability and PK of CS-1103, however there is no benefit to the healthy study participants. 
This study will provide a base of information for further development of this molecule, which 
has the potential to treat participants with meth intoxication. CS-1103 has been extensively 
evaluated in nonclinical studies. The development of hypersensitivity reactions in human 
participants is a potential risk. See Section 2.2.1 for additional information. More detailed 
information about the known and anticipated benefits as well as the risks, and reasonably 
expected AEs of CS-1103 may be found in the current IB.  
For the justification of the starting dose and provisionary dose range, see Sections 4.3 and 4.5. 
A comprehensive set of safety assessments have been implemented (see Section 8.2) along 
with well-defined study stopping criteria (see Section 4.6) to ensure participant safety. 
The Sponsor will immediately notify the Principal Investigator if any additional safety or 
toxicology information becomes available during the study. 
This study will be performed in compliance with the protocol, International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good 
Clinical Practice (GCP), and applicable regulatory requirements. 

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4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 1a, single center, double-blind, placebo-controlled, randomized, single 
ascending-dose first-in-human (FIH) study. The study will recruit up to 40 healthy normal 
participants, aged 18 to 55 years inclusive, with standard inclusion/exclusion criteria for 
healthy participant studies. Up to 5 cohorts of 8 participants (6 active, 2 placebo participants 
per cohort) will be enrolled with each participant assigned to receive a single dose of CS-1103 
or placebo on 1 occasion (Day 1). 
All participants will be screened within 28 days of dose administration and participants will 
check-in to the inpatient clinical research unit (CRU) on Admission/Day 1. Participants will 
be randomized on Day 1, the day prior to their schedule CS-1103 administration (after 
meeting all eligibility criteria). Participants are scheduled to remain in the CRU for up to 48 
hours postdose for safety and PK assessments. Participants will be discharged on Day 3 after 
completion of all scheduled assessments and will be asked to return to the CRU on Day 8 for 
the end of study (EOS) visit. Note: Discharge from the CRU may be delayed for up to 8 hours 
to optimize PK assessment (see Section 8.4.1). The study duration will be approximately 37 
days.  
All participants for a dose level may check-in to the CRU on the same date. However, each 
dose level will include 2 sentinel participants (1 active, 1 placebo) who will be dosed first and 
monitored by an Investigator for a minimum of 24 hours. The available safety and tolerability 
data from the sentinel participants, up to 24 hours post dose, will be reviewed by an 
Investigator. Following this safety data review, dosing of the remaining participants in the 
cohort may proceed (see Section 10.1.7.1). The remaining participants for each dose level will 
be randomized the day prior to dosing and will dose on Day 1, provided there are no safety or 
tolerability concerns, using a 5:1 randomization ratio to active or placebo study treatment 
separately for each dose level. A randomization list will be prepared for each cohort. See 
Section 4.5 for dose escalation details. 
Eligible participants will be randomized to 5 cohorts of 8 participants each. Each cohort will 
receive a single IV infusion of CS-1103 or placebo at one dose level. At each dose level, 
6 participants will receive CS-1103 and 2 participants will receive matching placebo. The 
starting dose and provisional subsequent dose levels are provided below: 
 Cohort 1: Dose level 1 (CS-1103 2.7 mg/kg, 
) or placebo (
) 
 Cohort 2: Dose level 2 (CS-1103 8.0 mg/kg, 
) or placebo (
) 
 Cohort 3: Dose level 3 (CS-1103 16.0 mg/kg, 
) or placebo (
) 
 Cohort 4: Dose level 4 (CS-1103 26.7 mg/kg, 
) or placebo (
) 
 Cohort 5: Dose level 5 (CS-1103 40.0 mg/kg, 
) or placebo (
) 

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 Note: The dose will be capped at 3000 mg. 
4.2 
Scientific Rationale for Study Design 
This is the FIH study to be conducted with CS-1103. It is designed to evaluate the safety, 
tolerability, and PK of CS-1103 in healthy participants at increasing doses when given as a 
single IV infusion. The study will be conducted in healthy participants who are free of 
underlying comorbidities to allow evaluation of CS-1103-related response. The schedule of 
safety and PK assessments and planned 48-hour in-house observation are targeted to an 
expected short half-life (t1/2) based on the nonclinical species evaluated. The 7-day follow-up 
period is consistent with that of other FIH studies. 
Scheduled activities during the Phase 1a clinical trial include careful monitoring of vital signs 
(systolic, diastolic, and mean blood pressure, pulse rate, respiratory rate, oxygen saturation, 
body temperature) and electrocardiogram (ECG) monitoring before, during, and after dosing. 
The proposed monitoring plan mitigates any potential risk for the Phase 1a clinical trial 
associated with respiratory or cardiovascular effects. 
4.3 
Justification for Dose 

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Additional details are provided in the current IB. 
4.4 
End of Study Definition  
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the schedule of activities (SoA) (Section 1.3), whichever is 
later.  
A participant is considered to have completed the study if he/she has completed all periods of 
the study including the last visit or the last scheduled procedure shown in the SoA Section 1.3. 
4.5 
Dose Escalation  
This initial dose will be a single IV infusion. An expected dose escalation will proceed with 
maximum incremental increase in dose not exceeding 3-fold at the lowest dose. Subsequent 
dose escalation will not exceed a 2-fold increase in dose and the incremental dose escalations 
are planned to decrease in size as CS-1103 dose rises. See Section 4.1 for the provisional 
CS-1103 doses for the subsequent cohorts and for additional details on screening and 
admission/discharge from the inpatient CRU. 
Dose escalation to the next dose level(s) will not proceed until the safety and tolerability of 
CS-1103 over at least 48 hours and plasma PK results scheduled over at least the 24 hour 
in-clinic assessment period have been evaluated for at least 6 of the 8 participants in the 
preceding dose cohort by the Safety Review Committee (SRC) (see Section 10.1.7.1). 
 
 
 
 
2 At a dose of 40.0 mg/kg CS-1103 in humans, the C0 is estimated at 340 µg/mL (220 µM) and AUC[0-tlast] is 
estimated at 318 µg·hr/mL. 

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4.6 
Study Stopping Criteria 
4.6.1 
Criteria for Stopping Dose Escalation 
Dose escalation will be stopped if any of the following study stopping rules are met:  
 One or more participants who received CS-1103 report a serious adverse events (SAEs) 
considered at least possibly related to the study treatment 
 Two or more participants who received CS-1103 experience a moderate AE in the same 
organ system that are at least possibly related to the study treatment 
 One or more participants who received CS-1103 fulfill Hy’s law defined as alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST)] >3 × the upper limit of 
normal (ULN) and total bilirubin >2 × ULN in the absence of significant increase 
(>2 × ULN) in alkaline phosphatase (ALP) and in the absence of an alternative diagnosis 
that explains the increase in total bilirubin, to be assessed from the first administration of 
study treatment up to and including follow-up/EOS Visit. The event must be considered at 
least possibly related to study treatment 
 Two or more participants, who receive CS-1103, have QTc prolongation defined as QT 
corrected for heart rate by Fridericia’s formula (QTcF) >500 msec, or an increase of QTcF 
>60 msec above baseline to a value >480 msec on the 12-lead ECG, confirmed (persistent 
for >5 min) on a repeat 12-lead ECG.  
 Any other event in CS-1103-treated participants occurs and is deemed by the SRC to pose 
an unacceptable risk to participants 
 Any participant exceeds predicted exposures equivalent to exposure limits 
 
; AUC(0-last) (456 
h/mL). If 
the predefined exposure limits are reached and there are no safety or tolerability concerns, 
a lower dose may be investigated. If any of these criteria are met, the SRC will stop further 
dose escalation. The SRC will determine whether a lower dose should be tested or whether 
the study should be terminated 
4.6.2 
Criteria for Stopping the Study 
If the Sponsor, Investigator, clinical monitor, or FDA officials discover conditions during the 
study that indicate that the study or a study site should be terminated, this action may be taken 
after appropriate consultation between the Sponsor, Investigator, and clinical monitor.  

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Provision of signed and dated, written informed consent prior to any study specific 
procedures. 
2. Healthy male and/or female participants aged 18 to 55 years, inclusive. 
3. A body mass index between 18.0 to 30.0 kg/m2, inclusive, and a minimum body weight of 
50 kg. 
4. Females must be of nonchildbearing potential, must not be lactating, must have a negative 
serum pregnancy test at the Screening Visit, and must have a negative urine pregnancy test 
on admission to the study site CRU. The nonchildbearing potential of the female 
participant will be confirmed at the Screening Visit by fulfilling 1 of the following criteria 
(see Section 10.4.1 for additional information): 
 Postmenopausal defined as amenorrhea for at least 12 months following cessation 
of all exogenous hormonal treatments and with follicle stimulating hormone (FSH) 
levels in the laboratory defined postmenopausal range. 
 Documentation of irreversible surgical sterilization by hysterectomy, bilateral 
oophorectomy or bilateral salpingectomy but not tubal ligation. 
5. Male participants should be willing to use double barrier contraception, i.e., condoms and 
spermicide, from the day of dosing until at least 90 days after dosing with the study 
treatment (see Section 10.4.2 for additional information). 
6. Male participants must agree not to donate sperm from the day of dosing until at least 
90 days after dosing with the study treatment. 
7. Considered generally healthy upon completion of medical history, physical examination, 
vital sign measurements, ECG, and clinical laboratory test results in the opinion of an 
Investigator at Screening and Admission/
1. 
8. Must agree to abstain from alcohol intake 48 hours before administration of the study 
treatment, during the confinement period of the study until after the final Follow-up/EOS 
Visit. 
9. Able to comply with the protocol and attend all scheduled visits. 
 

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5.2 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
1. History of any clinically important disease or disorder which, in the opinion of an 
Investigator, may either put the participant at risk because of participation in the study, or 
influence the results or the participant's ability to participate in the study. 
2. History or presence of gastrointestinal, hepatic or renal disease or any other condition 
known to interfere with absorption, distribution, metabolism or excretion of drugs. 
3. Estimated glomerular filtration rate <90 mL/min/1.73 m2 based on Modification of Diet 
and Renal Disease formula during Screening and on Admission/
1 (Table 6). 
4. Any current active infections, including localized infections, or any recent history (within 
1 week prior to study treatment administration) of active infections (including severe acute 
respiratory syndrome coronavirus 2 [SARS-CoV-2]), cough or fever, or a history of 
recurrent or chronic infections. 
5. Administration of any vaccine (live and inactivated [e.g., inactivated influenza vaccines or 
SARS-CoV-2 vaccines]) are not allowed within 2 weeks of dosing and while on study is 
prohibited.  
6. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of 
the first administration of study treatment or planned surgical procedure during the study 
period. 
7. Blood donation/blood loss greater than 500 mL during the 56 days prior to screening. 
8. Any positive result at the Screening Visit for serum hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV).  
9. Abnormal vital signs, after at least 5 minutes remaining in the supine position at the 
Screening Visit and on Admission/
1, defined as any of the following: 
 Systolic blood pressure >145 mmHg 
 Diastolic blood pressure >95 mmHg 
 Heart rate <45 or >100 bpm 
10. Any clinically significant abnormalities in rhythm, conduction or morphology of the 
resting ECG, and any clinically important abnormalities in the 12-lead ECG as considered 
by the Investigator that may interfere with the interpretation of QTc interval changes. 
11. Prolonged Fridericia QTcF >450 msec in males or >470 in females or shortened QTcF 
<340 msec or family history of long QT syndrome at the Screening Visit and on 
Admission/
1 
12. ALT and/or AST >1.0 × ULN at the Screening Visit and on Admission/
1. 
13. Current smokers, or those who have smoked or used nicotine products (including nicotine 
patches) within 1 month prior to dose administration (see Section 5.3.2 for additional 
details). 
14. History of alcohol abuse or excessive intake of alcohol as defined in Section 5.3.2. 

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15. Positive screen for drugs of abuse or cotinine at the Screening Visit or admission to the 
study site CRU or positive screen for alcohol on admission to the study site CRU prior to 
the first administration of study treatment (see Table 6). 
16. Positive test results for coronavirus disease 2019 (COVID-19) performed at admission to 
the CRU. 
17. History of severe allergy/hypersensitivity/anaphylaxis or ongoing clinically important 
allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to any 
components in the study treatment. 
18. Excessive intake of caffeine containing drinks or food (more than 6 cups of coffee or 
equivalent per day) (see Section 5.3.2 for definition of excessive). 
19. Treatment with prescription or nonprescription medications (including over-the-counter 
[OTC] medications, supplements, and herbal preparations such as St. John's Wort extract) 
within 14 days prior to start of study treatment, unless in the opinion of an Investigator and 
Sponsor the medication will not interfere with the study. See Section 6.6 for additional 
details. 
20. Has received an Investigational Product within 30 days or a biologic within 90 days 
(or 5 half-lives for both, whichever is longer) prior to screening.  
21. Consumption of poppy seeds, red wine, Seville oranges, Seville orange marmalade, 
grapefruit, or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit 
juices within the 7 days prior to Admission/
1 (see Section 5.3.1).  
22. Previous randomization to treatment in the present study. 
23. Involvement in the planning and/or conduct of the study (applies to the Sponsor, contract 
research organizations, and study site staff, etc.). 
24. Participants who are unlikely to cooperate with the requirements of the study. 
25. Judgment by the Investigator that the participant should not participate in the study if they 
have any ongoing or recent (i.e., during the screening period) minor medical complaints 
that may interfere with the interpretation of study data or are considered unlikely to 
comply with study procedures, restrictions and requirements. 
 
5.3 
Lifestyle Considerations 
5.3.1 
Meals and Dietary Restrictions 
 Refrain from consumption of poppy seeds, red wine, Seville oranges, Seville orange 
marmalade, grapefruit, or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, 
or fruit juices from 7 days prior to Admission/
1 and through the duration of the 
study (see Section 5.2, exclusion criteria 21). 
 At least a 10 hour overnight fast (with water ad libitum) is required prior to study 
treatment administration and a 4 hour fast is required following study treatment 
administration 

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 Participants will be asked to drink 360 mL of water after completion of their final predose 
urine void. After that no water is allowed until 1 hour after dose administration, after 
which time, water is allowed ad libitum. At 2 hours postdose, participants will be 
encouraged to drink another 360 mL of water. Participants are encouraged to drink at least 
1 L of water over the first 12 hours post drug administration (inclusive of the 2 × 360 mL 
of water specified above). If participants are unable to drink the complete 360 mL of 
water, the reason why and the exact amount consumed will be documented. 
5.3.2 
Caffeine, Alcohol, and Tobacco 
 Participants will abstain from ingesting excessive caffeine- or xanthine-containing 
products (e.g., coffee, tea, red bull, cola drinks, and chocolate [more than 6 cups of coffee 
or equivalent per day]) within 7 days prior to study treatment administration and through 
the final Follow-up/EOS Visit 
o One caffeine unit is contained in the following items: 1 (6 oz) cup of coffee, 
2 (12 oz) cans of cola, 1 (12 oz) cup of tea, ½ (4 oz) cup of energy drink (e.g., Red 
Bull), or 3 (1 oz) chocolate bars 
 Participants will abstain from alcohol intake 48 hours prior to study treatment 
administration and until after the final Follow-up/EOS Visit. History of alcohol abuse or 
excessive intake of alcohol defined as: 
o an average weekly intake of >14 drinks/week for men or >7 drinks/week for 
women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of wine or 
12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits 
 Use of tobacco products will not be allowed within 1 month prior to study treatment 
administration and through the final Follow-up/EOS Visit. 
5.3.3 
Activity 
 Participants should refrain from strenuous exercise for 72 hours before the screening 
medical examination, 72 hours before admission, and throughout the residential period in 
the CRU and again 72 hours before the scheduled Follow-up/EOS Visit. 
 Participants will be advised not to donate blood or plasma for at least 3 months after the 
last dose administration. 
 Participants will be asked to remain in the supine position during dose administration and 
for at least 40 minutes post-EOI 
 On days when digital ECG (dECG) Holter measurements are being taken, study 
participants should be restricted to a low level of physical activity and should refrain from 
any activities likely to stimulate or excite them (e.g., video games, stimulating movies, or 
television shows, etc.) during extraction timepoints. Additionally, participants should 

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refrain from using hand-held electronic or electrical devices (e.g., cell phones, hair dryers, 
etc.) as these have a potential to interfere with ECG signals. 
5.4 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical study 
does not meet all the eligibility criteria and is not subsequently randomly assigned to study 
treatment to enter the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants should be assigned a new participant number for every 
screening/rescreening event. 
5.5 
Criteria for Temporarily Delaying Enrollment/Randomization  
Enrollment and randomization can be paused, at the Sponsor’s discretion, in the event of 
restrictions related to the COVID-19 pandemic or a similar national emergency. 
As the COVID-19 pandemic may peak in different regions at different times and restrictions 
implemented by local laws and recommendations may vary, any decision on procedural 
changes should be made on a case-by-case basis by the Investigator in consultation with the 
study team and the medical team as needed, while maintaining participant safety and 
confidentiality as the priority. Management of COVID-19 risk post enrollment will be 
according to CRU specific procedures. 

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Intervention Name 
CS-1103 
Placebo 
Sourcing 
Provided centrally by the Sponsor  
Provided by clinical site 
Packaging and 
Labeling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The clinical site will provide 
commercially available 0.9% Sodium 
chloride for infusion. Each dose will be 
packaged and labeled per all applicable 
regulatory requirements. The volume 
(mL/kg) of the placebo treatment will 
match that of the CS-1103 treatment.  
Abbreviation: IMP = Investigational Medicinal Product; IV = intravenous. 
a Admission/
1 weight will be used for dose calculations. 
Note: CS-1103 dose administration will be based on the weight of the tetrasodium salt. 
bSee Pharmacy Manual for specifics for determining IV bag volume. 
6.2 
Preparation, Handling, Storage, and Accountability 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received, and any discrepancies are reported 
and resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized study 
site staff may supply or administer study treatment. All study treatment must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and authorized 
study site staff. 
The Investigator or delegated pharmacy staff is responsible for study treatment accountability, 
reconciliation, and record maintenance (i.e., receipt, reconciliation, and final disposition 
records). 
The Investigator, or delegated pharmacy staff must maintain an adequate record of the receipt 
and distribution of all study treatment using the Drug Accountability Form. These forms must 
be available for inspection at any time. 
Further guidance and information for packaging, storage, study treatment     
preparation/handling and the final disposition of unused study treatments are provided in the 
study site Pharmacy Manual outside of this protocol.  

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6.3 
Measures to Minimize Bias: Randomization and Blinding 
On 
1, the day prior to dosing, participants will be assigned a unique number 
(randomization number) in ascending numerical order at the CRU. The randomization number 
encodes the participant’s assignment to one of the study treatments of the study, according to 
the randomization schedule generated prior to the study by the Statistics Department at 
IQVIA. Each participant will be dispensed blinded study treatment, labeled with his/her 
unique randomization number, throughout the study. 
Participants who withdraw from the study for reasons other than AEs may be replaced at the 
discretion of the Sponsor. If a participant withdraws his/her participation in the study, then 
his/her randomization number cannot be reused. In the event that a participant is replaced, an 
unblinded pharmacy delegate at the site will utilize the randomization schedule to determine 
the appropriate randomization number for the replacement participant so that each 
replacement participant will be assigned to the appropriate treatment and will receive the same 
study treatment (CS-1103) or placebo as the participant being replaced. Randomization 
numbers for replacement participants will be assigned as follows: the original randomization 
number plus 100 (e.g., if the original participant being replaced had a randomization number 
of 1001, the replacement randomization number will be 1101). 
Sponsor safety staff may unblind the study treatment assignment for any participant with an 
SAE. If the SAE requires that an expedited regulatory report be sent to one or more regulatory 
agencies, a copy of the report, identifying the participant’s study treatment assignment, may 
be sent to Investigators in accordance with local regulations and/or Sponsor policy.  
In case of a medical emergency, an Investigator or authorized designee is allowed to break the 
code to determine treatment assignment. The Sponsor will be notified of the unblinding.  
After each dose cohort the SRC will determine the dosing regimen(s) for the next cohort (see 
Sections 6.5 and 10.1.7.1 for additional SRC details). This decision will generally be made 
without breaking the randomization code. If judged necessary by the SRC, an individual or the 
complete cohort may be unblinded during evaluation of the study data. Before unblinding, a 
decision should be made about the action to be taken based on the revealed treatment 
allocation. All decisions to unblind an individual or the complete cohort will be documented 
in writing. 
6.4 
Study Treatment Compliance 
Participants will receive study treatment directly from the Investigator or designee, under 
medical supervision. The start date and time and the end date/time of the IV infusion 
administered in the clinic will be recorded in the source documents. The volume infused will 
also be documented. Any interruptions in the infusion (stop/restart time) will also be 
documented, if applicable. The dose volume of study treatment and study participant 

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identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study treatment.  
6.4.1 
Study Treatment Strategy 
The clinical research facility is staffed 24 hours a day, 7 days a week with a minimum of one 
Advanced Cardiovascular Life Support certified safety personnel and a Basic Life Support 
certified personnel on site. Site safety measures for participants include crash cart with 2 jump 
bags, panic buttons located throughout the facility and strategically placed cameras. The 
clinical research facility is located within close proximity to multiple emergency rooms and 
hospitals and always has an Investigator (physician or nurse practitioner) on call 24 hours a 
day, 7 days a week for medical consultation by clinical staff, if needed.  
As this is the first administration of CS-1103 in humans, all effects cannot be reliably 
predicted. The preclinical data suggest an acceptable safety margin. Facilities and staff for 
resuscitation and the treatment of other medical emergencies will be provided. 
6.4.2 
Individual Study Treatment Adjustment/Interruption 
If a participant experiences a reaction symptom, the study treatment infusion should be 
stopped. The infusion may be restarted at a slower rate or halted entirely based on an 
Investigator’s discretion. Any interruptions (stop time/restart time) will be documented. 
6.5 
Dose Modification 
The full details of starting dose selection/dose justification, dose escalation, and study 
stopping criteria are described in Sections 4.3, 4.5, and 4.6 of this protocol, respectively. 
The decision to proceed to the next dose level of CS-1103 will be made by the SRC based on 
safety and tolerability through at least 48 hours and preliminary PK data through at least 
24 hours are obtained at the most recent dose level as well as cumulative data for at least 6 out 
of the 8 participants. The SRC may decide to increase the dose to the next higher planned dose 
level, increase the dose by a lesser margin, repeat, or reduce the dose to an intermediate dose 
level. The decision may also be made to stop dosing. 
6.6 
Concomitant Therapy 
Any medication or vaccine (including OTC or prescription medicines, recreational drugs, 
vitamins, minerals, and/or herbal supplements) that the participant is receiving within 1 month 
of study treatment administration, at the time of enrollment, and receives during the study 
must be recorded in the electronic case report form (eCRF) along with: 
 Reason for use 
 Dates of administration including start and end dates 

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 Dosage information including dose and frequency 
Any changes in prior or concomitant medications will also be recorded in the eCRF. 
Administration of any vaccine (live and inactivated [e.g., inactivated influenza vaccines or 
SARS-CoV-2 vaccines]) are not allowed within 2 weeks of dosing and while on study is 
prohibited.  
Participants must abstain from taking prescription or nonprescription drugs (including OTC 
medications, vitamins, dietary or herbal supplements, such as St John’s Wort extract) within 
14 days before the start of study treatment until completion of the study (Follow-up/EOS 
Visit), unless, in the opinion of the Investigator and Sponsor, the medication will not interfere 
with the study. 
Acetaminophen, at doses of 2 g/24 hours, but <1 g in 4 hours, is permitted for use any time 
during the study. Other concomitant medications which are considered necessary for the 
participant’s safety and wellbeing, may be considered on a case-by-case basis at the discretion 
of the Investigator in consultation with the medical monitor, if required, and recorded in the 
appropriate sections of the eCRF.  
6.7 
Monitoring and Management of Hypersensitivity Reactions 
See Section 2.2.1 and the IB for nonclinical background information related to 
hypersensitivity to CS-1103. 
Participants will be closely monitored and assessed for the development of signs and 
symptoms of hypersensitivity reactions, including anaphylaxis. For any hypersensitivity 
reaction, appropriate therapy should be instituted per standard of care. Administration of study 
treatment is to occur under close supervision of a physician and where full resuscitation 
equipment is immediately available. 

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7.0 DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific study sites or of the study as a whole are detailed in 
Section 10.1.11. 
The process for dose escalation and the stopping criteria for the study are described in 
Sections 4.5 and 4.6. 
7.1 
Discontinuation of Study Treatment 
Not applicable as this is a single dose study. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, 
positive COVID-19 test or suspected SARS-CoV-2 infection, or administrative reasons. This 
is expected to be uncommon. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted, as shown in the SoA (Section 1.3). See SoA for data to be collected at the time 
of study discontinuation and follow-up (Follow-up/EOS Visit) and for any further evaluations 
that need to be completed.  
The participant will be permanently discontinued from the study treatment and the study at 
that time. 
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the study site study records. 
Should a participant request or decide to withdraw from the study, all efforts must be made to 
complete and report the observations as thoroughly as possible up to the date of withdrawal. 
Participants withdrawing due to an AE should be followed up according to the follow-up/EOS 
Visit (see SoA, Section 1.3). 
Participants who voluntarily withdraw are termed dropouts. Dropouts and participants 
withdrawn due to protocol violations may be replaced following discussion with the Principal 
Investigator and Sponsor. 
Participants withdrawn due to an AE will not be replaced. 

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7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
 The study site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
 Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
 Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
 Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment. 
 Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
 Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
count) and obtained before signing of the informed consent form (ICF) may be utilized for 
screening or baseline purposes provided the procedures met the protocol-specified criteria 
and were performed within the timeframe defined in the SoA (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 450 mL.  
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples. 
When multiple procedures are scheduled at the same visit, the order of assessments will be, 
ECG procedures, vital signs, PK sample collection (nominal), questionnaire, and injection site 
assessment. All scheduled postdose times listed for the assessments in the SoA (Section 1.3) 
are relative to the start of the IV infusion unless there is a significant extension of the infusion 
duration or infusion interruption (see Table 2). 
8.1 
Efficacy Assessments 
Not applicable. 
8.2 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (see Section 1.3). 
The Investigator will be responsible for safety assessments and review of AEs. The SRC will 
use reports of AEs to determine if further investigation is required due to possible association 
with study procedures or study treatment. 

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8.2.1 
Physical Examinations 
Physical examination schedule/timepoints are detailed in Section 1.3. 
A complete physical examination will include, at a minimum, neurological assessments of the 
cardiovascular, respiratory, gastrointestinal, renal, and systems. Height/body mass index 
(BMI) (screening only) and weight will also be measured and recorded.  
A brief physical examination will include, at a minimum, assessments of the skin, lungs, 
cardiovascular system, renal, and abdomen (liver and spleen). 
8.2.1.1 
Injection Site Assessment 
Injection Site Reactions 
Injection site reactions will be monitored and assessed at the time points listed in the SoA 
(Section 1.3) until resolved. The Investigator will assess the following: 
1. Induration
2. Redness
3. Swelling
This will be done on a 4-point scale: 
0 = absent 
1 = mild 
2 = moderate 
3 = severe 
8.2.2 
Vital Signs 
Vital signs (to be taken before blood collection for laboratory tests) will be measured after 
remaining in a supine position for at least 5 minutes, following ECG collection, and will 
include body temperature, pulse rate, respiratory rate, oxygen saturation, and systolic and 
diastolic, and mean blood pressure. Three blood pressure measurements (3 consecutive blood 
pressure readings) will be recorded at intervals of at least 1 minute. The average of the 3 blood 
pressure, including the mean blood pressure readings will be recorded. 
At screening and Admission/
1 vital signs may be repeated up to 2 times for meeting 
inclusion/exclusion criteria.  
For detailed vital sign schedule/timepoints, see Table 1 and 
Table 2 in Section 1.3. 

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8.2.3 
Electrocardiograms 
8.2.3.1 
Safety ECGs 
Triplicate 12-lead ECG(s) will be obtained as outlined in the SoA (Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. Electrocardiograms will be obtained after remaining for 5 minutes in the supine 
position and collected before other simultaneously scheduled procedures, i.e., vital signs and 
blood collections. 
The ECG tracing should clearly identify the patient, include the date and time of the 
assessment, and include the signature and date of the person who made the local 
interpretation; the tracing will be archived at the study site. The site Investigator will read and 
evaluate the standard 12-lead ECG tracings and confirm the result and indicate “clinically 
significant,” or “not clinically significant” along with a date and signature/initials. Review of 
ECG, at the time of collection, will be entered into the eCRF. Abnormal, clinically significant 
ECG results will be recorded as AEs (see Section 8.3). Additional details on how ECG data 
will be managed and recorded will be provided in the Site Study Manual. 
During the 24-hour Holter-ECG monitoring, at each time point at which triplicate ECGs are 
required, 3 individual ECG tracings should be obtained as closely as possible in succession, 
but no more than 2 minutes apart. The full set of triplicates should be completed in less than 
4 minutes.  
For detailed ECG timepoints, see Table 1 and Table 2 in Section 1.3.  
 
8.2.3.2 
Holter-ECG Monitoring 
Continuous 24-hour Holter-ECG monitoring will be performed as outlined in the SoA 
Section 1.3. The ECGs will be extracted from Holter at predefined timepoints to be 
time-matched with PK samples as detailed in Table 1 and Table 2, Section 1.3. 
Date and time of intake (start and completion) of any food during the Holter-ECG recording 
period will be recorded on the source documents and eCRF. 
All ECGs for QT evaluation will be recorded by using high resolution (1,000 Hz) 12-lead 
digital Holter recorders provided by the ECG central laboratory. All Holter recording relevant 
procedures will be described in a manual provided by the central laboratory. 
The CRU staff involved in the recording of the Holter ECGs will receive a training 
comprising study participant preparation, electrode placement, recording of the Holter-ECG 
under resting conditions, and data upload from the Holter-ECG recorded. 

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The same recorder/model will be used for all recordings for a study participant. Prior to each 
recording, the Holter recorder should be loaded with fresh batteries. The date and time settings 
must be checked at the start of each study day and synchronized with an official timekeeper 
for all machines used in the study. 
Skin preparation must be thorough and electrode positions must be according to electrode 
positions recommended by the Laboratory Manual. Electrode positions will be marked with an 
indelible pen at the start of the study day to ensure exact reposition. 
The 12-lead dECGs for concentration QTcF analysis will be extracted by the designated 
central laboratory after the study participant has remained in the supine position for at least 
5 minutes. 
Triplicate 12-lead dECGs for safety monitoring will be extracted within a 5-minute window 
preceding and up to the specified ECG acquisition time point. 
Prior to conducting the concentration-QT analysis, a separate analysis plan will be prepared 
detailing the procedure and analysis. 
During extraction periods on days when dECG Holter measurements are being taken, study 
participants should be restricted to a low level of physical activity and should refrain from any 
activities likely to stimulate or excite them as outlined in Section 5.3.3 due to potential 
interference with ECG signals. Food and drink should be restricted as detailed in the protocol 
(see Section 5.3.1) as this also has the potential to affect ECG signals. 
IQVIA Connective Devices Team will provide the Holter monitor equipment, oversight, and 
central reads for this data. Detailed instructions regarding Holter Monitoring for the study is 
provided in the Site Study Manual. 
8.2.4 
Anxiety Symptoms Questionnaire 
The Anxiety Symptoms Questionnaire (ASQ) is a brief self-report questionnaire which 
measures frequency and intensity of symptoms and was developed to improve assessment of 
anxiety symptoms in a clinical setting. The ASQ will be performed at timepoints outlined in 
Section 1.3, after completion of all other simultaneously scheduled procedures to avoid 
interference with scheduled vital sign, ECG, and PK evaluation.  
Instructions will be provided to participants related to completing each questionnaire. 
8.2.5 
Clinical Safety Laboratory Tests 
See Table 6 in Section 10.2 for the list of clinical laboratory tests to be performed and the SoA 
(Section 1.3) for the timing and frequency. 

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Local laboratories will be utilized to process and provide results for clinical laboratory tests 
allowing for immediate participant medical management. The Investigator must review the 
laboratory report, document this review, and record any clinically significant changes 
occurring during the study as an AE. All AEs require appropriate follow-up as described in 
Section 8.3). The laboratory reports must be filed with the source documents.  
All laboratory tests with values considered abnormal and clinically significant from the time 
of study treatment administration to the end of the study should be repeated up to or until the 
values return to normal or baseline, or are no longer considered clinically significant by the 
Investigator or medical monitor. If clinically significant values do not return to 
normal/baseline within a period of time judged reasonable by the Investigator, the etiology 
should be identified, and the Sponsor notified. 
All protocol-required laboratory tests, as defined in Table 6 (Section 10.2), must be conducted 
in accordance with the Laboratory Manual and the SoA (Section 1.3). 
If laboratory values from non-protocol-specified laboratory tests performed at the institution’s 
local laboratory require a change in participant management or are considered clinically 
significant by the Investigator (e.g., SAE or AE or dose modification), then the results must be 
recorded. 
8.2.6 
Pregnancy Testing 
Women of nonchildbearing potential should only be included after a negative highly sensitive 
serum pregnancy test at screening and urine pregnancy test prior to study treatment 
administration. 
Additional urine pregnancy testing should be performed at times specified in the SoA 
(Section 1.3) and when pregnancy is otherwise suspected during the study.  
8.2.7 
Medical History/Demographics 
Surgical, and general medication history will be recorded in the eCRF. Medical history will 
include COVID-19 infection and treatments received, COVID-19 vaccination status 
(including date and vaccine type received).  
8.3 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 

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The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up on all AEs (see Section 8.3.3). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the signing of the ICF until the last study visit at the 
timepoints specified in the SoA (Section 1.3). All AEs will be collected from the start of study 
treatment until the last study visit at the timepoints specified in the SoA (Section 1.3). 
Medical occurrences that begin before the start of obtaining informed consent will be recorded 
as medical history/current medical conditions, not as AEs. All SAEs will be recorded and 
reported to the Sponsor or designee immediately and under no circumstance should this 
exceed 24 hours of the Investigator’s awareness of the event, as indicated in Section 10.3. The 
Investigator will submit any updated SAE data to the Sponsor or designee within 24 hours of 
their awareness of the updated information. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion 
of the study participation. However, if the Investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she considers the 
event/cause of death to be reasonably related to the study treatment or study participation, the 
Investigator must promptly notify the Sponsor or designee. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting safety reports are provided in Section 10.3. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is provided in 
Section 10.3. 

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8.3.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation.  
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then 
file it along with the IB and will notify the Institutional Review Board (IRB), if appropriate 
according to local requirements. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to Investigators as necessary. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study treatment and until 10 weeks after dosing 
with study treatment. If a pregnancy is reported, the Investigator will record pregnancy 
information on the appropriate form and submit it to the Sponsor or designee within 24 hours 
of learning of the female participant or female partner of male participant pregnancy and 
should follow the procedures outlined in Section 10.4. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication (or 
elective termination) of a pregnancy for medical reasons will be reported as an AE or SAE. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth, or neonatal death)], the Investigator will report according to the SAE 
reporting procedures described in Section 10.3. 
The participant/pregnant female partner will be followed to determine the outcome of the 
pregnancy e.g., until delivery of baby or for longevity. The Investigator will collect follow-up 
information on the participant/pregnant female partner and the neonate and the information 
will be forwarded to the Sponsor or designee. 
Any post-study pregnancy-related SAE considered reasonably related to the study treatment 
by the Investigator will be reported to the Sponsor as described in Section 8.3.4. While the 
Investigator is not obligated to actively seek this information in former study 

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participants/pregnant female partner, he or she may learn of an SAE through spontaneous 
reporting. 
Any female participant who becomes pregnant after the single dose administration of study 
treatment, may continue participating in the study to complete required assessments until 
Follow-up/EOS Visit.  
8.4 
Pharmacokinetics 
8.4.1 
Collection of Samples 
Blood samples of approximately 2 mL and pooled urine will be collected for measurement of 
plasma and urine concentrations of CS-1103; respectively, at times as specified in SoA 
(Section 1.3) and Table 2 during treatment. The timing of sampling may be altered during the 
course of the study based on newly available data (e.g., to obtain data closer to the time of 
peak plasma concentrations) to optimize the PK sample collection schedule for PK parameter 
calculations. Up to 2 additional blood collections may be added, pooled urine collections may 
be extended, and discharge may be delayed for up to 8 hours to optimize PK assessment 
without preparation of an amendment. The timing of PK (both plasma and urine) may be 
adjusted based on emerging data. In case that CS-1103 half-life is less than 4 hours, PK 
sampling may be discontinued at a time earlier than 48 hours. 
Blood samples will be taken either by direct venipuncture or an indwelling cannula inserted in 
a forearm vein. On the day of CS-1103 administration, samples should be collected in the 
contralateral (opposite) arm from the one being used for drug infusion. The actual date and 
time (24-hour clock time) of each sample will be recorded. Samples will be used to evaluate 
the PK of CS-1103-01. Each plasma sample will be divided into 2 aliquots (1 each [primary 
and a back-up]). Samples collected for analyses of CS-1103 plasma concentration may also be 
used to evaluate safety or efficacy aspects related to concerns arising during or after the study. 
The window for the blood collections is detailed in Table 2. 
Urine samples for the determination of CS-1103-01 will be collected over the pooled intervals 
as specified in Table 2, Section 1.3. The actual start and stop date/time of each pooled urine 
collection as well as the volume of each pooled collection will be recorded. The site will also 
document whether the entire voided urine was collected for each interval (and complete void 
volume was recorded). 
Blood and pooled urine samples will be collected, labeled, stored, and shipped as detailed in 
the Laboratory Manual. 

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8.4.2 
Determination of Drug Concentration 
Samples for the determination of CS-1103 in plasma and urine will be analyzed on behalf of 
the Sponsor using appropriate validated bioanalytical methods. Full details of the bioanalytical 
methods will be described in a separate Bioanalytical Report. Reported CS-1103 
concentrations will reflect the concentrations of the tetrasodium salt. 
All samples still within the known stability of the analyte of interest at the time of receipt by 
the bioanalytical laboratory will be analyzed. 
Samples collected from participant who received placebo will not be analyzed. 
Remaining plasma and pooled urine samples may be subjected to further analysis by the 
Sponsor or designee for the purpose of the development of additional bioanalytical assays 
and/or to investigate the presence of CS-1103 metabolic products, if applicable. Samples 
collected for analyses of CS-1103 (plasma) concentration may also be used to evaluate safety 
aspects related to concerns arising during or after the study. The bioanalytical laboratory 
personnel analyzing the PK samples will be unblinded. 
8.4.3 
Calculation of Derivation of Pharmacokinetic Variables 
Pharmacokinetic parameters will be derived using noncompartmental methods with Phoenix® 
WinNonlin® Version 8.3 or higher (Certara, L.P. Princeton, New Jersey, United States of 
America [USA]) and/or SAS® Version 9.4 or higher (SAS Institute, Inc., Cary, North 
Carolina, USA). Actual elapsed time from start of the IV infusion will be used for the final 
plasma PK parameter calculations. Nominal time from end of the IV infusion will be used for 
preliminary PK parameter calculations. 
The plasma PK parameters in Table 4 will be determined for CS-1103. A minimum of 3 
quantifiable postdose concentrations will be required for all calculations. 
Table 6 
Plasma Pharmacokinetic Parameters 
Pharmacokinetic Parameter 
Definition 
Cmax 
Maximum concentration, obtained directly from the observed concentration 
versus time data 
CEOI 
Concentration at the end of the 10-minute IV infusion 
tmax 
Time to Cmax 
AUC(0-inf) 
Area under the plasma concentration-time curve from time zero 
extrapolated to infinity, calculated by linear up/log down trapezoidal 
summation 
AUC(0-last) 
Area under the plasma concentration-time curve from time zero to the time 
of the last quantifiable concentration, calculated by linear up/log down 
trapezoidal summation 
CL 
Systemic clearance 

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Vz 
Volume of distribution  
Vss 
Steady-state volume of distribution 
t1/2 
Half-life; a minimum of 3 points will be used for estimation 
z 
Elimination rate constant 
Abbreviation: IV = intravenous. 
Note: No dose correction for the sodium salt will be required for dose-dependent parameters, as both CS-1103 
dose and plasma concentrations will be based on the weight of the tetrasodium salt. 
For this study, an extrapolation of 30% will be considered acceptable for considering 
AUC(0-inf) sufficiently well defined. Dose normalized exposure will also be determined. 
Additional plasma parameters may be calculated if deemed appropriate. Further details with 
respect to the PK analysis will be provided in the statistical analysis plan (SAP). 
Any preliminary plasma PK result for use by the SRC will be reported in a manner that 
maintains blinding of the treatment the participants have received unless otherwise requested 
by the SRC. The urine PK parameters in Table 5 will be determined for CS-1103. 
Table 7 
Urine Pharmacokinetic Parameters 
Pharmacokinetic Parameter 
Definition 
Ae(t1-t2) 
By-interval amount excreted in urine during the pooled collection interval 
from t1 to t2 
Ae(0-last) 
Cumulative amount excreted in urine during the pooled collection intervals 
fe(t1-t2) 
By-interval faction of dose (reported as percent) excreted in urine during the 
pooled collection interval from t1 to t2 
fe(0-last) 
Cumulative fraction of dose (reported as percent) excreted in urine during 
the pooled collection intervals 
CLr 
Renal clearance calculated as Ae(0-last)/AUC(0-last) 
Note: No dose correction for the sodium salt will be required for dose-dependent parameters, as both CS-1103 
dose and plasma concentrations will be based on the weight of the tetrasodium salt. 
 
Additional urine parameters may be calculated if deemed appropriate. Further details will be 
provided in the SAP. 
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
Sponsor and study site study files but will not constitute a protocol amendment. The IRB will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 
8.5 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 

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8.6 
Genetics 
Genetics are not evaluated in this study. 
8.7 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.8 
Immunogenicity Assessments 
Not applicable 
8.9 
Health Economics 
Health economics parameters are not evaluated in this study. 

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9.0 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
No formal statistical hypotheses are to be tested. 
9.2 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
 Safety Analysis Set: All participants who have received one dose of study treatment 
(CS-1103 or placebo) 
 Pharmacokinetic Analysis Set: All participants who have received one dose of 
CS-1103 and have at least 1 quantifiable plasma or urine postdose concentration, 
without protocol deviations or events expected to affect PK results 
9.3 
Statistical Analyses 
9.3.1 
General Considerations 
The SAP will be developed and will describe the participant analysis sets to be included in the 
analyses, and procedures for accounting for missing, unused, and spurious data. This section 
focuses on the summary of the planned statistical analyses of the primary and secondary 
endpoints. 
All analyses, summaries, and listings will be performed using SAS® software (Version 9.4 or 
higher). Results will be summarized by treatment and overall, where appropriate.  
The following descriptive statistics will be used as applicable to summarize the study data unless 
otherwise specified: 
 Continuous variables: Sample size (n), mean, standard deviation (SD), median, 
minimum (min), and maximum (max) 
 Summaries for plasma CS-1103 concentrations will include the coefficient of variation 
and PK parameter summaries will also include the geometric mean (except for tmax, 
which will only be presented as min, median, max) 
 Categorical variables: Frequencies and percentages 
Individual participant data will be presented in listings. 
All missing or incomplete safety and PK data, including dates and times, are treated as such. 
Missing test results or assessments will not be imputed. The handling of any missing, unused, 
and spurious data will be documented in the Clinical Study Report. 

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9.3.2 
Pharmacokinetic Analyses 
9.3.2.1 
PK Analysis 
The PK analysis will be performed on the PK Population. CS-1103 plasma concentrations and 
calculated plasma and urine PK parameters will be listed and descriptively summarized by 
treatment and scheduled time point, as applicable. Arithmetic mean (±SD) and individual 
CS-1103 plasma concentration versus time curves will be plotted on linear and 
semilogarithmic scale, and percent of dose recovered in urine over time will be presented 
graphically, as appropriate. Dose proportionality of PK parameters will be explored 
graphically and by using a power model, as appropriate. 
Scatter plots of individual values and geometric means of PK parameters, AUC(0-inf) (or 
AUC(0-last), if AUC(0-inf) is not calculable in most participant), Cmax (and CEOI, if appropriate) as 
well as dose-normalized exposure parameters versus dose will be presented (PK parameter 
definitions provided in Table 4). Geometric mean and individual cumulative percent CS-1103 
excreted in urine versus time curves will also be presented on linear scale. 
Further details with respect to the PK analysis will be provided in the SAP. 
9.3.2.2 
PK-PD Analysis 
As an exploratory analysis, concentration-QT relationship will be assessed using linear mixed 
effects modeling. The details of the model will be provided in the SAP. 
9.3.3 
Safety Analyses 
All safety analyses will be performed on the Safety Analysis Population. Adverse events will 
be coded using the latest version of the Medical Dictionary for Regulatory Activities 
(MedDRA). The overall number and percentage of participants with at least one AE (and 
SAE) will be tabulated. Placebo participants will be combined into 1 treatment cohort. 
Overall, AE data will be summarized by treatment received. The frequency of all treatment 
emergent AEs (TEAEs), TEAEs by severity as detailed in Section 10.3. All TEAEs by 
relationship to study treatment, SAEs, TEAEs leading to death, and TEAEs leading to 
discontinuation of the study will be tabulated by Preferred Term (PT) and System Organ Class 
(SOC) for each treatment cohort. Summary statistics, including change from baseline, for vital 
signs, laboratory parameters, and ECG intervals will be provided by treatment, visit, and time 
point, as appropriate. Shift tables for laboratory parameters at each postbaseline visit will be 
tabulated against baseline results showing frequency of laboratory parameter observed normal 
range indicator (Low, Normal, High). For ECG results, appropriate outlier tabulations for QT 
and QTcF will also be presented by treatment. Outliers for QT and QTcF defined under 
outcome measures will be summarized using counts and percentages by treatment and 
sampling time, if appropriate and using participant-level maximum over time by treatment. 
The following categories will be presented by treatment and overall for CS-1103: 

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 Outlier QT and QTcF intervals (450-480 ms, 480-500 ms and >500 ms) 
 Change from baseline in QT and QTcF intervals (30-60 ms and >60 ms) 
Results of the physical examinations (including injection site assessment) and the AQS will be 
listed and if appropriate, summarized by treatment. 
9.4 
Interim Analysis 
No formal interim analysis is planned. Preliminary PK parameters will be calculated using 
available quality-controlled CS-1103 concentrations and scheduled sampling times to support 
dose escalation decisions, as applicable. 
9.5 
Sample Size Determination 
The sample size for this study is based upon precedent set by other Phase 1 studies to gain 
preliminary measure of safety and CS-1103 PK characteristics in a healthy participant 
population and not on statistical considerations of power while exposing as few participants as 
possible to the study treatment and procedures. 
A sample size of 8 participants per dose level (6 active: 2 placebo) in this study design is 
expected to be sufficient to meet the objectives of this study. 

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10.0 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
international ethical guidelines 
 Applicable ICH GCP guidelines 
 Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB by the Investigator and reviewed and approved 
by the IRB before the study is initiated. 
Any amendments to the protocol will require IRB approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study participants.  
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The Investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB 
 Notifying the IRB of SAEs, or other significant safety findings as required by IRB 
procedures 
 Providing oversight of the conduct of the study at the study site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB, and all 
other applicable local regulations 
After reading the protocol, each Investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or representative. The study will not start at any study 
site at which the Investigator has not signed the protocol. 

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10.1.2 
Adequate Resources 
The Investigator is responsible for supervising any individual or party to whom the 
Investigator delegates study-related duties and functions conducted at the study site. 
If the Investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the Investigator/institution should ensure this individual or 
party is qualified to perform those study-related duties and functions and should implement 
procedures to ensure the integrity of the study-related duties and functions performed and any 
data generated. 
10.1.3 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.4 
Insurance 
The Sponsor has obtained liability insurance, which covers this study as required by local law 
and/or national regulations and/or ICH guidelines, whichever is applicable. The terms of the 
insurance will be kept in the study files. 
10.1.5 
Informed Consent Process 
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy, and data protection requirements, where applicable, 
and the IRB or study site. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant. 
A participant who is rescreened will sign another ICF and receive a new screening number. 
10.1.6 
Data Protection 
 Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant 

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names or any information which would make the participant identifiable will not be 
transferred. 
 The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must also 
be explained to the participant who will be required to give consent for their data to be 
used as described in the informed consent. 
 The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB members, and by inspectors from regulatory authorities. 
10.1.7 
Committees Structure 
10.1.7.1 
Safety Review Committee 
A SRC has been appointed for this study. The SRC is a group of clinicians and/or scientists 
who are appointed to monitor the safety and scientific integrity of a human research 
intervention, and to make recommendations regarding for escalation to the next planned dose 
level, escalation to an intermediate dose (a dose lower than the next planned dose), repeating a 
dose level, suspension of the dose escalation until further review of study data can be made, as 
to whether the stopping rules have been met, or stop dose escalation and termination of the 
study, etc. The composition of the committee is dependent upon the scientific skills and 
knowledge required for monitoring the particular study. 
The SRC will consist, at a minimum, of the Principal or Sub-Investigator, Medical Monitor, 
and Sponsor’s qualified designee. The SRC is responsible for reviewing and evaluating 
blinded safety and PK data for the most recently dosed cohort, cumulatively obtained data, 
and subsequently at regularly scheduled meetings and for the dose selection during dose 
escalation. The committee may also meet in ad hoc meetings at its discretion as needed in 
response to events occurring in the study. 
Participant safety will be continuously monitored by the SRC, which includes safety signal 
detection at any time during the study. 
In addition, an early aggregated safety data review will be performed, the goal of which is to 
allow for a cautious, stepwise approach to study treatment administration/dose escalation. An 
initial sentinel safety review by an Investigator for this study is planned for the first 
2 participants who are dosed in each of the 5 cohorts and have provided safety and tolerability 
data for 24 hours after administration of a single dose prior to dosing the remaining 
participants within each cohort (see Section 4.1). 
All safety results for at least 48 hours and preliminary PK data through at least Day 2 
(24 hours postdose) for at least 6 out of the 8 participants within a cohort will be summarized 

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and reviewed by the SRC for agreement of next steps in dose escalation, due to the short 
half-life of the compound.  
In particular, data will be reviewed by the Sponsor for identification of events that would 
potentially contribute to a requirement to pause/stop dose escalation or the study. See 
Section 4.6 for stopping criteria details.  
Enrollment will be paused during the review. If a stopping rule is met, a decision will be 
made, based on the review, as to whether enrollment in the study will be allowed to resume. 
Case unblinding may be performed for above reviews if necessary. 
The details regarding SRC meeting frequency, data to be reviewed, the data review process, 
and information dissemination to clinical sites, are included in the SRC charter. 
10.1.8 
Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor will submit to any relevant database a summary of 
the results of the clinical study within 1 year from the end of the global clinical study. It shall 
be accompanied by a summary written in a manner that is understandable to laypersons. 
10.1.9 
Data Quality Assurance 
 All participant data relating to the study will be recorded on printed or eCRFs unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the case report form (CRF). 
 Guidance on completion of eCRFs will be provided in eCRF Completion Guidelines. 
 The Investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source data documents. 
 Quality tolerance limits will be predefined in the Integrated Project Management Plan to 
identify systematic issues that can impact participant safety and/or reliability of study 
results. These predefined parameters will be monitored during the study, and important 
deviations from the quality tolerance limits and remedial actions taken will be summarized 
in the clinical study report. 
 Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management 
and mitigation strategies and analytical risk-based monitoring), methods, responsibilities, 
and requirements, including handling of noncompliance issues and monitoring techniques 
(central, remote, or on-site monitoring) are provided in the Study Monitoring Plan. 
 Details of study monitoring, including action required due to SARS-CoV-2/COVID-19, 
will be included in a separate Study Monitoring Plan.  

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 The Sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
 The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
 Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator for 15 years after study completion unless local 
regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor. 
10.1.10 
Source Documents 
The Investigator/institution should maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study site’s participants. 
Source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, should not obscure the original entry, 
and should be explained if necessary (e.g., via an audit trail). 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in the monitoring 
guidelines and eCRF completion guidelines. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized study site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.11 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date and first act of recruitment is the date on which the clinical study will be 
open for recruitment of participants.  

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Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The Investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but 
are not limited to: 
For study termination: 
 Discontinuation of further study treatment development 
For study site termination: 
 Failure of the Investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
 Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the Investigator 
 Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the participant and should 
assure appropriate participant therapy and/or follow-up. 
10.1.12 
Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study site will be set forth in the Clinical Trial Agreement. 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before 
submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 

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multicenter studies only in their entirety and not as individual study site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
 
 

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Notification of SAE information via telephone does not replace the need for the Investigator 
to complete, sign and submit the paper SAE report form to the Sponsor or designee within 
24 hours of the Investigator’s awareness of the event. 
 
Contacts and methods for SAE reporting can be found in Safety Management Plan. 
 
 

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10.4 Appendix 4: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information 
10.4.1 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
NOTE: Documentation can come from the study site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high FSH level in the postmenopausal range may be used to confirm 
a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a 
single FSH measurement is insufficient. 
10.4.2 
Contraception Guidance 
Male Participants 
The following text is required ONLY until it has been determined that WOCBP who are 
partners of male participants no longer need protection from potential exposure to study 
treatment in seminal fluid and should be provided by the Sponsor and/or medic. For genotoxic 
study treatment, or for non-genotoxic study treatment with demonstrated or suspected human 
teratogenicity/fetotoxicity at subtherapeutic exposure levels where it is theoretically possible 
that relevant systemic concentrations may be achieved in WOCBP from exposure to seminal 
fluid, to prevent exposure of an embryo/fetus, the following text is required.  
 Male participants with female partners of childbearing potential are eligible to participate 
if they agree to ONE of the following during the protocol-defined time frame in 
Section 5.1:  
o Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent for 
duration of study and at least 90 days after dosing with the study treatment. 

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o Agree to use a male condom with spermicide and have their partner use a 
contraceptive method with a failure rate of <1% per year when having penile-vaginal 
intercourse with a WOCBP who is not currently pregnant. 
 In addition, male participants must refrain from donating sperm for the duration of the 
study and for at least 90 days after dosing with the study treatment.  
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent 
from penile-vaginal intercourse or use a male condom during each episode of penile 
penetration from the day of dosing until at least 90 days after dosing with the study 
treatment. 
Female Participants 
Female participants of childbearing potential are not eligible to participate. 
Pregnancy Testing: 
 Pregnancy testing should be performed at times specified in the SoA (Section 1.3) and as 
required locally. 
 Additional pregnancy testing may be performed at any time during the study based on an 
Investigator’s discretion when pregnancy is suspected.  
 Pregnancy testing, with a sensitivity of 5 mIU/mL will be performed using the test kit 
approved by the Sponsor and in accordance with instructions provided in its package 
insert. 
Collection of Pregnancy Information 
Male Participants With Partners Who Become Pregnant  
 The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This 
applies only to male participants who receive CS-1103. 
 After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor or designee within 24 hours of learning of the partner’s 
pregnancy. The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to the 
Sponsor. Generally, the follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any termination of the pregnancy will be reported regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure.  
Female Participants Who Become Pregnant  
 The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on the 
appropriate form and submitted to the Sponsor or designee within 24 hours of learning of a 

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participant’s pregnancy. The participant will be followed to determine the outcome of the 
pregnancy. The Investigator will collect follow-up information on the participant and the 
neonate and the information will be forwarded to the Sponsor or designee. Generally, 
follow-up will not be required for longer than 6 to 8 weeks beyond the estimated delivery 
date. Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
 While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
will be reported as an AE or SAE. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (i.e., spontaneous abortion, stillbirth, neonatal death, 
or congenital anomaly [including that in an aborted fetus, stillbirth, or neonatal death]), the 
Investigator will report according to the SAE reporting procedures described in 
Section 10.3. 
 Any post-study pregnancy-related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to the Sponsor or designee as described in 
Section 10.3. While the Investigator is not obligated to actively seek this information in 
former participants, he or she may learn of an SAE through spontaneous reporting.  
 Any female participant who becomes pregnant after the single dose administration of the 
study treatment may continue participating in the study to complete required assessments 
including Follow-up/EOS Visit. 
 
 

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10.5 Appendix 5: Abbreviations  
Abbreviation 
Definition 
Ae(t1-t2) 
By-interval amount excreted in urine during the pooled 
collection interval from t1 to t2. 
Ae(0-last) 
Cumulative amount excreted in urine during the pooled 
collection intervals. 
ADL 
Activities of Daily Living 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AQS 
Anxiety Symptoms Questionnaire 
AST 
Aspartate aminotransferase 
AUC 
Area under the plasma concentration-time curve 
AUC(0-inf) 
Area under the plasma concentration-time curve from time zero 
extrapolated to infinity, calculated by linear up/log down 
trapezoidal summation 
AUC(0-last) 
Area under the plasma concentration-time curve from time zero 
to the time of the last quantifiable concentration, calculated by 
linear up/log down trapezoidal summation 
CEOI 
Concentration at the end of the 10-minute intravenous infusion 
CFR 
Code of Federal Regulations 
CL 
Systemic clearance 
CLr 
Renal clearance 
COVID-19 
Coronavirus disease 2019 
C0 
Plasma drug concentration extrapolated to end of injection in 
the animal studies 
Cmax 
Maximum concentration, obtained directly from the observed 
concentration versus time data 
CRF 
Case report form 
CRU 
Clinical Research Unit 
dECG 
Digital electrocardiogram 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of Study 

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Abbreviation 
Definition 
FDA 
Food and Drug Administration 
fe(0-last) 
Cumulative fraction of dose excreted in urine during the pooled 
collection intervals 
fe(t1-t2) 
By-interval fraction of dose excreted in urine during the pooled 
collection interval from t1 to t2 
FIH 
First-in-human 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HED 
Human equivalent dose 
HIV 
Human immunodeficiency virus 
HRT 
Hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IRB 
Institutional Review Board 
IV 
Intravenous 
Max 
Maximum 
Min 
Minimum 
z 
Elimination rate constant 
NOAEL 
No-observed-adverse-effect-level 
OTC 
Over-the-counter 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QTcF 
QT corrected for heart rate by Fridericia’s formula 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SD 
Standard deviation 
SoA 
Schedule of activities 
SOC 
System Organ Class 

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Abbreviation 
Definition 
SRC 
Safety Review Committee 
t½ 
Half-life 
tmax 
Time to Cmax 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
Vss 
Volume of distribution at steady-state following intravenous 
dosing 
Vz 
Volume of distribution following intravenous dosing 
WOCBP 
Women of childbearing potential 
 
 

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11.0 REFERENCES 
1. Preliminary Findings from Drug-Related Emergency Department Visits, 2021: Results 
from the Drug Abuse Warning Network (HHS Publication No. PEP22-07-03-001). 
Subst. Abus. Ment. Heal. Serv. Adm. 2021. 
2. Hedegaard H, Bastian BA, Trinidad JP, Spencer MR, Warner M. Regional Differences 
in the Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 
2017. Natl Vital Stat Rep. 2019;68(12):1-16. 
3. Ahmad F, Cisewski J, Rossen L, Sutton P. Provisional Drug Overdose Death Counts. 
Natl. Cent. Heal. Stat. 2022. 
4. Ganapati S, Grabitz SD, Murkli S, et al. Molecular Containers Bind Drugs of Abuse in 
Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in 
Rats. Chembiochem. 2017;18(16):1583-8. https://doi.org/10.1002/cbic.201700289. 
5. Hoffmann U, Grosse-Sundrup M, Eikermann-Haerter K, et al. Calabadion: A new 
agent to reverse the effects of benzylisoquinoline and steroidal neuromuscular-
blocking agents. Anesthesiology. 2013;119(2):317-325. 
https://doi.org/10.1097/ALN.0B013E3182910213. 
6. Thevathasan T, Grabitz SD, Santer P, et al. Calabadion 1 Selectively Reverses 
Respiratory and Central Nervous System Effects of Fentanyl in a Rat Model. Br. J. 
Anaesth. 2020,125(1): e140-e147. https://doi.org/10.1016/j.bja.2020.02.019. 
7. Grabitz SD, Ganapati S, Cotten JF, Isaacs L, Eikermann M. Calabadion 1 Binds 
Cocaine In Vitro and Reverses Cocaine’s Behavioral Effects Dose-Dependently In 
Vivo. Anesthesiol. Annu. Meet. 2015. 
8. Logan BK, Fligner CL, Haddix T. Cause and manner of death in fatalities involving 
methamphetamine. J Forensic Sci. 1998;43(1):28-34. 
https://doi.org/10.1520/jfs16085j. 
9. 
hamphetamine blood concentrations in 
human abusers: application to pharmacokinetic modeling. Synapse. 
2007;61(4):216-220. https://doi.org/10.1002/syn.20365. 
10. Guidance for Industry: M3(R2) Nonclinical Safety Studies for the Conduct of Human 
Clinical Trials and Marketing Authorization for Pharmaceuticals (January 2010). 
 

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Protocol CS-1103-01, Version 3.0 Amendment 2 
 
Signature of Investigator 
PROTOCOL TITLE: A Phase 1a, Randomized, Double-Blind, Placebo-Controlled, Single 
Center Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CS-1103 
Following Single, Ascending Intravenous Dose Administration in Healthy Participants 
PROTOCOL NO: 
CS-1103-01 
VERSION:  
 
Version 3.0 Amendment 2 
This protocol is a confidential communication of Clear Scientific, Inc. I confirm that I have 
read this protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from the 
Sponsor. 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy to IQVIA, Inc.  
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:     __________________________            Date: ________   
Printed Name:                         ___________________________ 
Investigator Title:                    ___________________________ 
 
Name/Address of Center:               
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________