Clinical trial NCT03363841
Conditions: Candidiasis, Invasive Candidemia
Keywords: Candida auris
Sponsor: Scynexis, Inc.
Start date: 2017-11-15; Completion date: 2023-05-24
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a multicenter, open-label, non-comparator, single-arm study to evaluate the efficacy, safety, tolerability and PK (pharmacokinetics) of oral SCY-078 as an emergency use treatment for patients with a documented Candida auris infection.

Detailed description:
This is a multicenter, open-label, non-comparator, single-arm study to evaluate the efficacy, safety, tolerability and PK (for a subset of subjects) of oral SCY-078 in male and female subjects ≥18 years of age with a documented Candida auris infection. Patients will be treated with SCY-078 for up to 90 days.

Subjects must have a documented candidiasis, including candidemia, caused by Candida auris to be considered for enrollment. Subjects are also eligible if they are receiving intravenous (IV) antifungal therapy for their C. auris infection and, in the judgment of the investigator, continued IV antifungal therapy is not feasible or desirable due to clinical or logistical circumstances. Subjects must meet all study criteria to be eligible for inclusion. Inclusion of each subject in the study must be approved by the Sponsor prior to enrollment.

Following a screening visit , there will be up to 11 treatment visits, a follow-up visit and 2 follow-up contacts (survival visits)

Arms: arm 1: SCY-078
Interventions: intervention 1: SCY-078
Intervention descriptions: intervention 1: Oral SCY-078

Protocol documents:
Prot_000.pdf: 
 
 
SCYNEXIS, Inc. 
Clinical Trial Protocol 
Open-Label Study to Evaluate the Efficacy, Safety, Tolerability and 
Pharmacokinetics of SCY 078 in Patients with Candidiasis, Including 
Candidemia, Caused by Candida auris 
SCYNEXIS Protocol Number SCY-078-305 
 
SCYNEXIS, Inc. 
101 Hudson Street, Suite 3610 
Jersey City, NJ 07302 
06Oct2017 
NCT03363841 
 
            
 
  
US IND Number 107,521 
STATEMENT OF CONFIDENTIALITY 
The information in this document contains trade secrets and commercial information 
that are privileged or confidential and may not be disclosed unless such disclosure is 
required by federal or state law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure 
will apply equally to all future information supplied to you which is indicated as 
privileged or confidential. 


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1.0 
Contact Information 
 
   Contract Research Organization 
 
Study Medical Monitor 
 
Clinical Project Manager 
 
Safety Contact 
Sponsor 
 
 
 


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2.0 
Protocol Approvals 
 
PROTOCOL ID: SCY-078-305 
 
Open-Label Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of 
SCY 078 in Patients with Candidiasis, Including Candidemia, Caused by Candida auris 
SCYNEXIS, Inc. Approval: 
 
 
 
 
 
 
 
Date 
 


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Investigator Agreement Statement 
PROTOCOL ID: SCY-078-305 
Open-Label Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of 
SCY 078 in Patients with Candidiasis, Including Candidemia, Caused by Candida auris 
 
I understand that all documentation provided to me by SCYNEXIS, Inc. or its designated 
representative(s) concerning this study that has not been published previously will be kept 
in the strictest confidence. This documentation includes the study protocol, Investigator’s 
Brochure, case report forms, and other scientific data. This study will not commence 
without the prior written approval of a properly constituted Institutional Review Board or 
Ethics Committee. No changes will be made to the study protocol without the prior written 
approval of SCYNEXIS, Inc. and the Institutional Review Board/Ethics Committee, except 
where necessary to eliminate an immediate hazard to the patient. All patients will provide 
a written informed consent prior to participation. 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I have read, understood and 
agree to abide by all the conditions and instructions contained in this protocol, and in 
compliance with International Conference on Harmonization (ICH) guidelines, Good 
Clinical Practices (GCP), Safety Reporting obligations and any applicable local 
requirements. 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
Principal Investigator’s Name (Printed) 
 
 
 
 


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3.0 
Table of Contents 
1.0 
Contact Information ................................................................................................ 2 
2.0 
Protocol Approvals ................................................................................................. 3 
3.0 
Table of Contents .................................................................................................... 5 
4.0 
Revision History ................................................................................................... 10 
6.0 
Abbreviations ........................................................................................................ 11 
7.0 
Protocol Synopsis.................................................................................................. 14 
8.0 
Schematic of Study Design ................................................................................... 20 
9.0 
Background Information and Scientific Rationale ............................................... 21 
9.1 
Background Information ............................................................................... 21 
9.2 
Rationale for the Study ................................................................................. 25 
10.0 
Study Objectives ................................................................................................... 25 
10.1 
Primary Objectives ........................................................................................ 25 
10.2 
Secondary Objectives .................................................................................... 25 
10.3 
Exploratory Objectives ................................................................................. 25 
11.0 
Study Endpoints .................................................................................................... 26 
11.1 
Primary Endpoints ........................................................................................ 26 
11.2 
Secondary Endpoints .................................................................................... 26 
11.3 
Exploratory Endpoints .................................................................................. 26 
12.0 
Study Design ......................................................................................................... 27 
12.1 
Overall Description of the Study .................................................................. 27 
12.2 
Blinding, Randomization and Stratification ................................................. 28 
12.3 
Study Duration .............................................................................................. 28 
12.4 
Number of Subjects and Centers ................................................................... 28 
13.0 
Study Population ................................................................................................... 29 
13.1 
Inclusion Criteria .......................................................................................... 29 
13.2 
Exclusion Criteria ......................................................................................... 30 
13.3 
Discontinuation Criteria ................................................................................ 31 


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13.4 
Replacement of Dropouts ............................................................................. 32 
14.0 
Study Treatments .................................................................................................. 32 
14.1 
Study Treatment Groups ............................................................................... 32 
14.2 
Dietary Requirements ................................................................................... 32 
14.3 
Study Drugs .................................................................................................. 33 
14.3.1 
SCY-078 Description ................................................................................ 33 
14.3.2 
Formulation, Packaging and Labelling ..................................................... 33 
14.3.3 
Storage and Stability ................................................................................. 34 
14.4 
Drug Accountability...................................................................................... 34 
14.5 
Subject Compliance with Study Drug Dosing .............................................. 35 
15.0 
Non-Study Treatments .......................................................................................... 35 
15.1 
Prior and Concomitant Medications ............................................................. 35 
15.2 
Prohibited Medications ................................................................................. 36 
15.3 
Medications to be Administered with Caution and Monitored as Appropriate
 
36 
15.4 
Study Restrictions ......................................................................................... 36 
    16.0            Study Procedures ......................................................................................... 36 
16.1 
Informed Consent.......................................................................................... 36 
16.2 
Inclusion and Exclusion Criteria ................................................................... 37 
16.3 
Subject Enrollment and Assignment of Subject Number ............................. 37 
16.4 
Medical History and Demographics ............................................................. 37 
16.5 
General Physical Examination ...................................................................... 37 
16.6 
Vital Signs ..................................................................................................... 38 
16.7 
Twelve-Lead Electrocardiogram .................................................................. 38 
16.8 
Pregnancy Test .............................................................................................. 38 
16.9 
Targeted Physical Examination, Including Clinical Evaluation of Signs and 
Symptoms of Infection .................................................................................................. 38 
16.10 
Mycological Testing ..................................................................................... 39 
16.11 
Imaging ......................................................................................................... 39 


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16.12 
Serological Testing ....................................................................................... 39 
16.13 
Safety Laboratory Tests ................................................................................ 39 
16.14 
Pharmacokinetic Sample Collection (PK Subset Only)................................ 41 
16.15 
Efficacy Assessment ..................................................................................... 41 
16.16 
Study Drug Dispensing, Collection and Treatment Compliance Evaluation 42 
16.17 
Study Drug Dosing ....................................................................................... 42 
16.18 
Subject Diary Dispensing, Collection and Review ....................................... 43 
16.19 
Prior and Concomitant Medication Review .................................................. 43 
16.20 
Adverse Event Monitoring ............................................................................ 43 
17.0 
Study Schedule...................................................................................................... 44 
18.0 
Safety Assessments and Monitoring ..................................................................... 46 
18.1 
Definition of an Adverse Event .................................................................... 46 
18.2 
Definition of a Serious Adverse Event ......................................................... 47 
18.3 
Events of Clinical Interest ............................................................................. 47 
18.4 
Overdose ....................................................................................................... 48 
18.5 
Pregnancy ...................................................................................................... 48 
18.6 
Unexpected Adverse Event ........................................................................... 48 
18.7 
Grading of Adverse Events ........................................................................... 49 
18.8 
Causality Assessment.................................................................................... 49 
18.9 
Adverse Event Collection Timeframe .......................................................... 49 
18.10 
Serious Adverse Event Reporting Requirements .......................................... 50 
18.11 
Adverse Event and Serious Adverse Event Follow-up ................................. 50 
18.12 
Serious Adverse Event Reporting – Procedures for Investigators ................ 50 
18.13 
Procedures for Emergency Unblinding ......................................................... 51 
19.0 
Data Collection, Study Monitoring and Record Management .............................. 51 
19.1 
Data Collection and Reporting ...................................................................... 51 
19.2 
Study Monitoring .......................................................................................... 51 
19.3 
Investigator Study Files ................................................................................ 51 
19.4 
Retention of Records ..................................................................................... 52 


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20.0 
Analytical Plan ...................................................................................................... 52 
20.1 
Sample Size Determination ........................................................................... 53 
20.2 
Analysis Populations ..................................................................................... 53 
20.3 
Subject Disposition, Discontinuation, and Baseline Data ............................ 53 
20.4 
Handling of Missing Data, Dose Adjustments, and Early Withdrawals ....... 54 
20.5 
Prior and Concomitant Medications ............................................................. 54 
20.6 
Pharmacokinetics (PK Subset Only) ............................................................. 54 
20.6.1 
Pharmacokinetic Assessments .................................................................. 54 
20.6.2 
Pharmacokinetic Analyses ........................................................................ 54 
20.7 
Efficacy ......................................................................................................... 55 
20.7.1 
Efficacy Assessments ................................................................................ 55 
20.7.2 
Efficacy Analyses ..................................................................................... 56 
20.8 
Safety ............................................................................................................ 57 
20.8.1 
Safety Assessments ................................................................................... 57 
20.8.2 
Safety Analyses ......................................................................................... 57 
21.0 
Ethics and Protection of Human Patients .............................................................. 58 
21.1 
Ethical Conduct of the Study ........................................................................ 58 
21.2 
Institutional Review Board/Ethics Committee Review ................................ 58 
21.3 
Informed Consent.......................................................................................... 58 
21.4 
Future Use of Samples .................................................................................. 58 
21.5 
Subject Privacy and Subject Confidentiality ................................................ 59 
21.6 
Study Termination ........................................................................................ 59 
21.7 
Financial Disclosure ...................................................................................... 59 
22.0 
References ............................................................................................................. 60 
23.0 
Appendices ............................................................................................................ 62 
23.1 
Appendix A:  Prohibited Medications and Medications to be Administered 
with Caution .................................................................................................................. 62 
23.1.1 
Prohibited Medications ............................................................................. 62 


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23.1.2 
Medications to be administered with Caution and Monitored as Appropriate
 
63 
 
LIST OF FIGURES 
Figure 1 Schematic of Study Design ............................................................................. 20 
Figure 2 Chemical Structure of SCY-078 Citrate .......................................................... 33 
LIST OF TABLES 
Table 1: Schedule of Treatment Visits and Procedures (Study SCY-078-305) ............. 44 
Table 2 Schedule of Survival Visits and Procedures (Study SCY-078-305) ................. 45 
 
 
 
 


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Revision History 
Not applicable 
 
 


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6.0 
Abbreviations 
ABBREVIATION 
DEFINITION 
aPTT 
activated partial thromboplastin 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BID 
twice daily 
BUN 
blood urea nitrogen 
CD 
compact disk 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL/F 
clearance/fraction 
CLSI 
Clinical and Laboratory Standards Institute 
Cmax 
maximum concentration 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CT 
computerized tomography 
CYP 
cytochrome P450 
DMC 
Data Monitoring Committee 
DVD 
digital versatile disk 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECI 
event of clinical interest 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EoT 
end of treatment 


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ABBREVIATION 
DEFINITION 
EUCAST 
European Committee on Antimicrobial Susceptibility Testing 
FDA 
Food and Drug Administration 
FU 
follow-up 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
IB 
Investigator´s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
identification 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ITT 
intent to treat 
IV 
intravenous 
LDH 
lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
minimum inhibitory concentration 
MRI 
magnetic resonance imaging 
NG 
nasogastric 
OTC 
over-the-counter 
PEG 
percutaneous endoscopic gastrostomy 
PI 
principal investigator 
PK 
pharmacokinetics 
Pop PK 
population pharmacokinetics 
PP 
per protocol 
PT 
prothrombin time 
QD 
once daily 
QTcF 
QTc interval corrected for heart rate using Fridericia´s correction 


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ABBREVIATION 
DEFINITION 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SOC 
standard of care 
TT 
thrombin time 
ULN 
upper limit of normal 
US 
United States 
VVC 
vulvovaginal candidiasis 
WBC 
white blood cell 
WT 
wild type 
β-hCG 
β-human chorionic gonadotropin 
 
 
 
 


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7.0 
Protocol Synopsis 
 
Title: Open-Label Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of 
SCY 078 in Patients with Candidiasis, Including Candidemia, Caused by Candida auris 
Primary Objectives:  
 
To evaluate the efficacy of SCY-078 as determined by a Data Monitoring Committee 
(DMC) by assessing global success (composite assessment of clinical and mycological 
success) at End of Treatment (EoT). 
Secondary Objectives:  
 
To evaluate the safety and tolerability of SCY-078 
 
To evaluate the efficacy of SCY-078 by measuring recurrence of the baseline fungal 
infection 42 days after EoT (Week 6 Follow-up) 
 
To determine the efficacy of SCY-078 by measuring subject survival 42 and 84 days 
after Day 1 (first dose of study drug) 
Exploratory Objectives 
 
To evaluate the efficacy of SCY-078 as determined by the DMC by assessing additional 
efficacy outcomes at EoT 
 
To evaluate the efficacy of SCY-078 as determined by the investigator by assessing 
select efficacy outcomes at EoT 
 
To determine the interpretative breakpoint of SCY-078 against C. auris  
 
To evaluate the pharmacokinetics (PK) of SCY-078 by population PK analysis (for a 
subset of subjects) 
Primary Endpoints: 
 
Efficacy as measured by the percentage of subjects with global success (complete or 
partial global response) at EoT as determined by the DMC 
Secondary Endpoints:  
Safety and tolerability as measured by: 
 
Physical examination, vital signs, 12-lead electrocardiogram (ECG), safety laboratory 
tests, adverse events (AEs) and treatment discontinuations 
 
The percentage of subjects with treatment-emergent AEs 
Efficacy as measured by: 
 
The percentage of subjects with a recurrence of the baseline fungal infection 42 days 
after EoT (Week 6 Follow up) 
 
The percentage of subjects surviving 42 and 84 days after Day 1 (first dose of study 
drug) 
Exploratory Endpoints: 
 
Percentage of subjects with complete global response at EoT, as determined by the DMC 
 
Percentage of subjects with partial global response at EoT, as determined by the DMC 
 
Percentage of subjects with stable disease at EoT, as determined by the DMC 
 
Percentage of subjects with progressive disease at EoT, as determined by the DMC 
 
Percentage of subjects with clinical success at EoT, as determined by the investigator 


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 
Percentage of subjects with mycological success at EoT, as determined by the 
investigator 
 
Percentage of subjects with global success at EoT, as determined by the investigator 
 
Analysis of response by minimum inhibitory concentration (MIC) based on CLSI M27-
A3 in vitro method    
 
SCY-078 plasma concentration by population PK analysis (for a subset of subjects) 
Study Phase: 3 
Study Design: This is a multicenter, open-label, non-comparator, single-arm study to evaluate 
the efficacy, safety, tolerability and PK (for a subset of subjects) of SCY-078 in male and female 
subjects ≥18 years of age with a documented Candida auris infection.   
Study Population: Subjects must have a documented candidiasis, including candidemia, caused 
by Candida auris to be considered for enrollment. Subjects are also eligible if they are receiving 
intravenous (IV) antifungal therapy for their C. auris infection and, in the judgment of the 
investigator, continued IV antifungal therapy is not feasible or desirable due to clinical or 
logistical circumstances. Additionally, subjects must be able to tolerate medication orally or 
through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube to be able 
to participate in the study. Subjects must meet all study criteria to be eligible for inclusion. 
Inclusion of each subject in the study must be approved by the Sponsor prior to enrollment. 
The study will be conducted at approximately 10 sites globally, and is planned to enroll and treat 
approximately 30 subjects.  
Study Treatments: Eligible subjects will receive an initial oral loading dose of 750 mg of SCY-
078 (3 tablets of 250 mg) twice a day (BID) during the first 2 days of treatment and then 
subsequent oral doses of 750 mg once a day (QD) for up to 90 days. 
Study Visits: The study will consist of a combined Screening and Treatment Day 1 (Baseline) 
visit to determine subject eligibility and begin study treatment; a Treatment Day 2 visit for PK 
sampling (only for subjects who participate in the PK portion of the study); 2 additional 
scheduled treatment visits (Treatment Days 3 to 5 and Treatment Days 7 to 10) and treatment 
visits every 14 days thereafter (for up to a total of 90 days) to continue study treatment and 
perform clinical, mycological, imaging, serological and safety assessments, and to collect PK 
samples (only for subjects who participate in the PK portion of the study); an EoT visit to assess 
primary and exploratory efficacy outcomes; 1 follow-up (FU) visit 6 weeks after EoT (Week 6 
Follow-up) to assess recurrence (secondary efficacy endpoint) and safety; and 2 survival 
visits/contacts to determine survival status (alive or deceased). 
Efficacy: Efficacy will be assessed primarily in terms of global success (defined as a complete 
or partial global [clinical and mycological] response) at EoT as determined by the DMC. 
Secondary efficacy assessments will include recurrence (after EoT) and survival. Recurrence 
will be assessed by measuring recurrence of the baseline fungal infection 42 days after EoT 
(Week 6 FU). Survival will be determined on Day 42 and Day 84 (42 and 84 days after the 
Screening/Treatment Day 1 visit [first dose of study drug]).  This can be an in-person visit or a 
phone contact, and will document subject status only (alive or deceased). If subject is deceased, 
the relationship to the fungal infection will be recorded. 
Complete global response, partial global response, stable disease and progressive disease at EoT 
as determined by the DMC will be assessed as exploratory efficacy endpoints.  Global success, 
clinical success and mycological success at EoT as determined by the investigator will also be 
assessed as exploratory efficacy endpoints. 


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The following study procedures will be performed to assess treatment outcome: clinical signs 
and symptoms of candidiasis; radiological assessments including esophagoscopy and other 
imaging scans, as applicable (e.g., X-ray, ultrasound, CT and MRI); mycological testing (fungal 
cultures); and serological testing (ß-(1,3)-D glucan). 
Pharmacokinetics: PK analyses will be performed for subjects who give their consent to 
participate in the PK portion of the study (the PK Subset). Blood samples will be collected on 
Treatment Day 2 (one sample collected anytime post dosing), Treatment Days 3 to 5 (one sample 
collected predose on any of these days) and Treatment Days 7 to 10 (one sample collected 
predose on any of these days). 
Safety: Subjects will be evaluated for safety throughout the study, including parameters such as 
physical exam, vital signs, 12-lead ECGs, safety laboratory tests (hematology, blood chemistry 
and urinalysis), AEs, treatment discontinuations and concomitant medications. A final safety 
assessment will be conducted at the Week 6 Follow-up visit (6 weeks after the EoT). 
Analyses: Results from the study will be analyzed against historical SoC-treated subjects, who 
will be selected from literature reviews and other data resources, and be based on the 2015 
Infectious Diseases Society of America guidelines for the management of candidiasis. 
Target Population: Subjects ≥18 years of age with documented candidiasis, including 
candidemia, caused by Candida auris. 
KEY Inclusion Criteria:  
Subject must fulfill the following KEY criteria to be eligible for study admission: 
1. 
Subject is a male or female adult ≥ 18 years of age on the day the study informed consent 
form (ICF) is signed. 
2. 
Subject has a documented candidiasis, including candidemia, caused by Candida auris. The 
subject is also eligible if he/she is receiving IV antifungal therapy for their C. auris infection 
and, in the judgment of the investigator, long-term IV antifungal therapy is not feasible or 
desirable due to clinical or logistical circumstances. 
A documented candidiasis, including candidemia, caused by Candida auris is defined as 
the recovery of Candida auris by culture of a sample obtained within the last 7 days.  
3. 
Subject is able to tolerate medication orally or through a nasogastric (NG) tube or 
percutaneous endoscopic gastrostomy (PEG) tube. 
 
KEY Exclusion Criteria: 
A subject will be excluded from participation in the study if he or she meets any of the following 
KEY exclusion criteria: 
1. 
Subject has a fungal disease with central nervous system involvement. 
2. 
Subject has a fungal disease of the bone and/or joint that is expected to require >90 days of 
study drug treatment. 
3. 
Subject has an inappropriately controlled fungal infection source (e.g. persistent catheters, 
devices, identified abscess) that is likely the source of the fungal infection.  
4. 
Subject is hemodynamically unstable and/or requiring vasopressor medication for blood 
pressure support. 
5. 
Subject has abnormal liver test parameters: AST or ALT >10 x ULN, and/or total bilirubin 
>5 x ULN.  
 
Note: Subjects with unconjugated hyperbilirubinemia with diagnosis of Gilbert’s disease 
are not excluded.  
6. 
Subject has an Apache score >16.  
7. 
Subject has serum creatinine >3 times from Baseline (Screening/Treatment Day 1) value. 


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8. 
Subject has a prolonged QTcF interval (Fridericia’s correction: QTc= QT/(RR)0.33) 
>480 ms on the baseline ECG or other abnormalities deemed clinically significant by the 
investigator that would put the subject at unacceptable risk for participation in the study. 
Study Drugs: SCY-078 citrate drug product for oral administration will be supplied as a tablet 
containing 250 mg of SCY-078 active ingredient on a free-base basis. In addition to the active 
ingredient, the tablet formulation also contains silicified microcrystalline cellulose, 
crospovidone, mannitol, colloidal silicon dioxide, magnesium stearate (non-bovine) and 
butylated hydroxyanisole. 
SCY-078 tablets are to be stored at room temperature, between 15C and 30C.  
Randomized Treatment Groups: This is an open-label, single-arm study. There will be no 
randomization or stratification for this study. Eligible subjects must be approved by the sponsor 
for enrollment. 
Subjects will receive an initial oral loading dose of 750 mg of SCY-078 (3 tablets of 250 mg) 
twice a day (BID) during the first 2 days of treatment and then subsequent oral doses of 750 mg 
once a day (QD) for up to 90 days. 
Study Blinding:  Open-label study 
Pharmacokinetic Evaluations (PK Subset Only): PK testing will be conducted for subjects 
who give their consent to participate in the PK portion of the study (the PK Subset). Up to three 
(3) blood samples will be collected at the following visits and sampling windows: Treatment 
Day 2 (one sample collected anytime post dosing), Treatment Days 3 to 5 (one sample collected 
predose on any of these days) and Treatment Days 7 to 10 (one sample collected predose on any 
of these days). 
The sparse samples collected in this study will be analyzed using Population PK (Pop PK) 
analysis methods to estimate PK parameters (Cmax, AUC, clearance/fraction absorbed [CL/F]) as 
applicable. 
Efficacy Evaluations: Efficacy will be assessed primarily in terms of global success (defined as 
a complete or partial global [clinical and mycological] response) at EoT as determined by the 
DMC. Complete global response, partial global response, stable disease and progressive disease 
at EoT as determined by the DMC will be assessed as exploratory endpoints.  Global success, 
clinical success and mycological success at EoT as determined by the investigator will also be 
assessed as exploratory endpoints. 
The following treatment outcome definitions will be used for the assessment of efficacy: 
Global Outcome 
Global outcome will be scored as global success (complete global response or partial global 
response) or global failure (stable disease or progressive disease) 
Global success: Global success is defined as a complete global response or a partial global 
response 
 
Complete global response is defined as a complete clinical response (the resolution of all 
clinical signs and symptoms and/or radiological abnormalities from baseline attributable to 
the Candida auris infection) and a mycological response (mycological clearance (direct 
and/or negative cultures [when obtainable] and/or normal serological results [when 
appropriate]) 
 
Partial global response is defined as a partial clinical response (major improvement of all 
clinical signs and symptoms and/or radiological abnormalities from baseline attributable to 
the Candida auris infection) and a mycological response (mycological clearance (direct 
and/or negative cultures [when obtainable] and/or normal serological results [when 
appropriate]) 
Global failure: Global failure is defined as either stable disease and/or progressive disease 


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 
Stable disease is defined as minor or no clinical improvement but without deterioration 
and/or unchanged serological response. 
 
Progressive disease is defined as clinical deterioration necessitating alternative antifungal 
therapy or resulting in death, and/or worsened serological response, and/or persistence of 
fungal infection on the basis of culture, microscopic evaluation, or histopathological testing. 
Clinical Outcome 
Clinical success: clinical success is defined as a complete clinical response (the resolution of all 
clinical signs and symptoms and/or radiological abnormalities from baseline attributable to the 
Candida auris infection) or a partial clinical response (major improvement of all clinical signs 
and symptoms and/or radiological abnormalities from baseline attributable to the Candida auris 
infection).  
Mycological Outcome 
Mycological success: mycological success is defined as a mycological response (mycological 
clearance (direct and/or negative cultures [when obtainable] and/or normal serological results 
[when appropriate]). 
Efficacy assessments will also include recurrence (after EoT) and survival. Recurrence will be 
assessed by measuring recurrence of the baseline fungal infection 42 days after EoT (Week 6 
FU). Survival will be determined on Day 42 and Day 84 (42 and 84 days after 
Screening/Treatment Day 1 [first dose of study drug]).  
Recurrence: recurrence is defined as global success at EoT but re-emergence of the baseline 
Candida auris infection during the post treatment follow-up.  Re-emergence of the Candida 
auris infection is required to be with the same species and involving the same site that was 
initially identified at Screening/Treatment Day 1.  
Safety Evaluations:  
Subjects will be evaluated for safety and tolerability throughout the study, including parameters 
such as physical exam, vital signs, 12-lead ECGs, safety laboratory tests (hematology, blood 
chemistry and urinalysis), concomitant medications, AEs and treatment discontinuations. 
Statistical Analyses:  
Descriptive statistics (i.e., number of subjects, mean, standard deviation, median, minimum, 
maximum) will be presented for all continuous variables; number and percentage of subjects will 
be presented for categorical variables. For parameters measured over time, observed data and 
changes from baseline will be described for each time point. 
All analyses of the study results for SCY-078 will be descriptive. Unless otherwise stated, data 
will be analyzed as is with no imputation. 
Sample Size Determination: This is an exploratory study and no formal sample size calculation 
was performed. A total of 30 subjects are estimated to be adequate for an assessment of the safety 
and tolerability of SCY-078 in subjects with candidiasis, including candidemia, caused by C. 
auris.  
Analysis Populations: 
 
Intent-to-Treat (ITT) Population: The ITT population will include all subjects who are 
enrolled in the study.  
 
Per-Protocol (PP) Population: The PP population will include all ITT subjects who receive 
at least 10 total days of antifungal therapy (SCY-078), who have an EoT assessment and 
who have no major protocol violations that would impact the assessment of efficacy.  
 
Safety Population: The safety population will include all subjects who receive at least one 
dose of study medication and have at least one safety assessment post baseline. 


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 
PK Population: The PK population will include all enrolled subjects who provide at least 
one PK sample. 
Pharmacokinetic Analyses (PK Subset Only):  
The PK analysis will be conducted on the PK Population. The concentration versus time data 
from the sparse PK samples collected in this study will be analyzed using a Pop PK model to 
estimate Cmax, AUC and CL/F, as applicable. Further analysis of possible metabolites may be 
performed. 
Efficacy Analyses: 
The primary efficacy endpoint, the percentage of subjects with global success (defined as a 
complete or partial global [clinical and mycological] response) as determined by the DMC at 
EoT, will be presented with a 95% confidence interval (CI) for the ITT and PP populations.  
Secondary and exploratory categorical endpoints will be presented with 95% CIs for the ITT and 
PP populations. 
The percentage of subjects surviving at 42 and 84 days after Screening/Treatment Day 1 (first 
dose of study drug) will be presented for the ITT and PP populations; Kaplan-Meier curves will 
be presented. 
Safety Analyses:  
All safety analyses will be conducted using the safety population; all safety variables will be 
listed. The incidence and severity of treatment-emergent AEs and SAEs and their relationship to 
treatment will be summarized.  AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) Version 19.1 or higher and presented by system organ class and preferred 
term.   
Early discontinuation of study drug treatment will be presented and will include the reasons for 
and timing of such discontinuations. Prior and concomitant medications will be summarized; 
medications will be classified based on the World Health Organization´s Drug Dictionary 
terminology. 
Abnormal physical examinations will be listed. Laboratory evaluations will be summarized as 
observed values and changes from Baseline; shifts with respect to the laboratory reference range 
will be summarized. Vital signs and ECG evaluations will be summarized as observed values 
and changes from Baseline. 
 
 


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8.0 
Schematic of Study Design 
 
 
 
 
Figure 1 
Schematic of Study Design 
 
End of Treatment (EoT) 
(up to 90 days of treatment 
with SCY-078) 
Week 6 Follow-up 
(6 weeks after EoT) 
 
 
Visit 1 – Screening/Treatment Day 1 
(Day -1 to Day 1) 
 
Survival Day 42 
(42 days after Treatment Day 1) 
Survival Day 84  
(84 days after Treatment Day 1)
Visit 2 - PK Sample collection 
(PK subset only) (Day 2) 
Visit 3 (Treatment Days 3 to 5) 
Visit 4 (Treatment Days 7 to 10) 
Visits 5-10 (every 14 days thereafter up to End of Treatment 


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9.0 
Background Information and Scientific Rationale 
9.1 
Background Information 
Candida is among the most common causes of healthcare-associated bloodstream infections in the 
United States (US), with an estimate of 46,000 healthcare-associated Candida infections occurring 
among hospitalized patients in the US each year. The CDC surveillance data have reported that 
approximately 7% of all Candida bloodstream isolates tested are resistant to fluconazole and some 
Candida strains are increasingly resistant to first-line and second-line antifungal treatment agents, 
including azoles and echinocandins.1 Centers specialized in the treatment of immune-
compromised patients report increased frequency of non-albicans species of Candida with higher 
incidence of resistance. For example, in a survey conducted in the MD Anderson Cancer Center, 
Houston, Texas, US (2005–2013), out of 146 isolates of C. glabrata evaluated, 30 (20.5%) were 
resistant to fluconazole; 15 (10.3%), to caspofungin; and 10 (6.8%), to multiple drugs.2 Roughly, 
30% of patients with drug-resistant Candida bloodstream infections (candidemia) due to drug-
resistant Candida die during their hospitalization. 
Candida auris is an emerging fungus that presents a serious global health threat. Healthcare 
facilities in several countries have reported that C. auris has caused severe illness in hospitalized 
patients. Some strains of Candida auris are resistant to all three major classes of antifungal drugs. 
This type of multidrug resistance has not been seen before in other species of Candida. Also of 
concern, C. auris can persist on surfaces in healthcare environments and spread between patients 
in healthcare facilities, unlike most other Candida species.3  
SCY-078 is a member of a new class of antifungal agents and is an orally active, semi-synthetic, 
triterpene derivative of the natural product enfumafungin. SCY-078 is a structurally distinct class 
of glucan synthase inhibitor that inhibits the synthesis of the fungal cell wall polymer β-(1,3)-D-
glucan. Time kill studies have demonstrated that SCY-078 has fungicidal in vitro activity against 
Candida spp. isolates similar to that observed with the echinocandins. 
While three classes of antifungal agents (azoles, echinocandins and polyenes) are currently 
available to treat Candida  infections, the emergence of resistance to azoles and echinocandins as 
well as the toxicity associated with polyenes signals the need for new agents that are well tolerated 
and retain activity against resistant strains. SCY-078 represents the first compound of the triterpene 
class of β-(1,3)-D-glucan synthesis inhibitors in development for the treatment of fungal 
infections. It is structurally distinct and retains activity in vitro against both azole-resistant and, 
importantly, the majority of clinical isolates containing FKS gene mutations, which confer 
echinocandin resistance. Unlike echinocandins, SCY-078 is orally bioavailable, with in vitro and 
in vivo activity against Candida and Aspergillus species and, as such, it would represent the first 
oral non-azole treatment alternative for these infections.  SCY-078 is being developed as the first 
oral and intravenous (IV) glucan synthase inhibitor for the treatment and prevention of fungal 


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infections caused by Candida and Aspergillus species with the potential to provide the therapeutic 
advantages of both an IV and oral formulation. 
 
Activity against Candida spp. 
SCY-078 has been evaluated against >1600 Candida isolates, including all clinically relevant 
species, more than 400 C. glabrata isolates and >100 C. auris isolates.4,5 These in vitro studies 
have demonstrated the broad range of anti-Candida spectrum of activity of SCY-078. 
Additionally, SCY-078 demonstrated in vitro activity against pre-formed biofilms,6 which is a 
relevant feature when addressing catheter-related Candida infections. Studies conducted with 
azole- and echinocandin-resistant strains have shown that SCY-078 retains activity (i.e., no 
significant change in minimum inhibitory concentration MIC] when compared to wild type) 
against >90% of azole-resistant strains and >70% of Candida strains with FKS mutations 
commonly associated with echinocandin resistance.7 Interestingly, although SCY-078 and the 
echinocandins share a similar mechanism of action (β-[1,3]-D-glucan synthesis inhibition), their 
clearly different molecular structure provides them with some differentiating characteristics in 
terms of microbiological activity.  
SCY-078 was evaluated in vitro against >170 clinical isolates of echinocandin-resistant strains of 
Candida spp., >95% of which contained mutations in the FKS gene. Overall, SCY-078 was active 
against the majority of the echinocandin-resistant strains tested. Significantly, SCY-078 was active 
against approximately 70% of the isolates containing the most commonly reported FKS mutation 
associated with echinocandin resistance in C. glabrata (S663P in FKS2 and S645P in FKS1).7 
Selection of SCY-078 resistance in vitro occurs at a low frequency. A deletion at position F659 in 
FKS2 of C. glabrata was the predominant mutation observed in these studies; notably, SCY-078 
did not select for mutations at positions S663 or S645.8 These results suggest that SCY-078 inhibits 
glucan synthase in a manner different from that of echinocandins.  
SCY-078 has also demonstrated a potent activity against life-threatening C. auris strains. SCY-
078 has been evaluated against >100 clinical C. auris strains, approximately 20 of which were 
drug resistant.5 SCY-078 demonstrated efficacy against both wild type (WT) and drug-resistant 
isolates in these studies at concentrations indicative of potential clinically relevant effect. Candida 
auris is an emerging, multi-resistant yeast that can cause invasive infections and is associated with 
high mortality. It is typically resistant to fluconazole and exhibits markedly variable susceptibility 
to other azoles, amphotericin B and echinocandins.4,9,10 It is currently recognized to be the first 
exogenous candida infection.  C. auris has been recently highlighted as a clinical alert by the 
Centers for Disease Control and Prevention (CDC) because of the global emergence of this fungal 
infection with limited therapeutic options and high mortality.   


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Antifungal activity  
The spectrum and potency of activity of SCY-078 has been evaluated by numerous independent 
laboratories against an extensive panel of clinically relevant yeast and mold isolates using the 
Clinical and Laboratory Standards Institute (M27-A3 guidelines)4,11 and European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) methods. Overall, the epidemiological studies 
have demonstrated that SCY-078 has potent, broad-spectrum activity against the majority of the 
clinical isolates tested. These studies have laid the foundation in support of the use of SCY-078 
for the treatment of invasive fungal infections.  
 
Murine models of invasive fungal infections  
The antifungal efficacy of SCY-078 has been evaluated in several murine models of disseminated 
candidiasis and aspergillosis. In a disseminated C. albicans model, SCY-078 was more active than 
fluconazole at all doses. Murine models of SCY-078 in disseminated candidiasis caused by C. 
glabrata and C. tropicalis indicated activity across multiple Candida species. The SCY-078 area 
under the curve (AUC) in plasma necessary to achieve target efficacy in these models was 
estimated to be 15.4 ± 2.2 μM•hr. Also, in an invasive murine model for C. auris, dose-related 
improvements in survival and reductions in kidney fungal burden were observed. 
In a murine model of disseminated A. fumigatus infection that evaluated both WT and azole-
resistant strains, treatment with SCY-078 resulted in improved survival and significant decreases 
in kidney fungal burden at all doses. The exposure needed to achieve efficacy is in line with 
efficacious exposures reported in the invasive candidiasis models. 
The data available from all of the in vitro and in vivo studies conducted to date provide significant 
support for the use of SCY-078 in the treatment of invasive fungal infections.  
 
Nonclinical experience  
Toxicology studies in rats and dogs have been conducted with the oral formulation of SCY-078 
administered for up to 90 days. The results from these studies indicate that SCY-078 is well 
tolerated and support the doses and treatment duration intended in this study.  
The in vitro studies indicated that SCY-078 metabolism was predominantly oxidative, with 
cytochrome P450 (CYP) 3A being the primary enzyme involved in its oxidative metabolism. 
Strong inhibitors of CYP3A would be expected to increase plasma levels of SCY-078; therefore, 
the concurrent administration of SCY-078 with such inhibitors should be avoided.  
 
 


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Clinical experience  
To date, over 300 subjects and patients have received either oral or IV formulations of SCY-078 
in Phase 1 and Phase 2 studies.  
SCY-078 was generally well tolerated following single oral doses of up to 1600 mg and multiple 
oral doses of up to 800 mg/day for 28 consecutive days in Phase 1 studies. Reported adverse events 
(AEs) after oral administration have been generally transient and primarily mild to moderate in 
intensity. The most frequently reported AEs have been mild gastrointestinal events (nausea, 
vomiting, diarrhea and abdominal pain).  
A Phase 2 study of oral SCY-078 as step-down therapy from IV echinocandin in patients with 
invasive candidiasis has been completed. This was a multicenter, randomized, open-label study in 
which, following three to ten days of IV echinocandin therapy, 21 patients received either SCY-
078 500 mg once daily (QD) with a 1000 mg loading dose (6 patients), SCY-078 750 mg QD with 
a 1250 mg loading dose (7 patients) or standard of care (SOC) treatment (8 patients with either 
oral fluconazole 400 mg QD with an 800 mg loading dose or IV micafungin 100 mg QD for up to 
28 days). SCY-078 was well tolerated in this study, with an AE profile typical of this population 
and comparable to the SOC. The results from this study also indicated that the higher dose of SCY-
078 tested (750 mg QD) is predicted to achieve the target exposure at steady state in the majority 
of patients.  
A Phase 2 proof-of-concept study of oral SCY-078 in patients with vulvovaginal candidiasis 
(VVC) has also been completed. In this multicenter, randomized, active-controlled, evaluator-
blinded study of oral SCY-078 compared to oral fluconazole in adult female patients with VVC, 
96 patients with an acute, moderate to severe, symptomatic episode of VVC were randomized in 
a 1:1:1 ratio to receive either oral SCY-078 750 mg with a 1250 mg loading dose for three days, 
oral SCY-078 750 mg with a 1250 mg loading dose for five days or a single dose of oral 
fluconazole. SCY-078 was well tolerated, with the most common AEs being mild gastrointestinal 
events. The high clinical cure rates observed in this study are supportive of the clinically relevant 
antifungal activity of SCY-078 in this form of Candida infection.  
Several drug-drug interaction studies have been conducted. Ketoconazole (a strong inhibitor of 
CYP3A) induces a significant (5-fold) increase in SCY-078 exposure, while diltiazem (a moderate 
inhibitor of CYP3A) induces a mild to moderate (<3 fold) increase in SCY-078 exposure. SCY-
078 did not have any effect on rosiglitazone (a CYP2C8 substrate) exposure, had only a mild effect 
(less than a 0.5-fold increase) on the AUC of tacrolimus (a CYP3A and P-gp substrate) and had 
no effect on the maximum concentration (Cmax) of tacrolimus. 
SCY-078 has the potential to be an important addition to the anti-fungal treatment arsenal by 
providing potent activity against the full spectrum of Candida species, including difficult-to-treat 
organisms, and by affording the added flexibility of both oral and IV formulations.  
For additional information on SCY-078, please refer to the Investigator´s Brochure (IB).  


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9.2 
Rationale for the Study 
This study is being conducted to evaluate the efficacy, safety, tolerability and PK (for a subset of 
subjects) of SCY-078 in male and female subjects >18 years of age with a documented Candida 
auris infection.  
The primary efficacy endpoint of the study is global success, defined as either a complete or partial 
global (clinical and mycological) response. The primary endpoint will be determined at the end of 
treatment (EoT).12,13  Clinical response will be evaluated by the signs and symptoms of the 
infection and/or imaging scans, if applicable. Mycological response will be assessed by fungal 
culture and serological testing (β-(1,3)-D-glucan),14 if applicable. Recurrence will be assessed 42 
days after the EoT (Week 6 Follow-up) as a secondary efficacy endpoint. Recurrence is defined as 
global success at EoT but re-emergence of the baseline Candida infection (with the  same Candida 
species and involving the same site) during the post treatment follow-up.13   
10.0 Study Objectives 
10.1 
Primary Objectives 
 To evaluate the efficacy of SCY-078 as determined by a Data Monitoring Committee (DMC) 
by assessing global success (composite assessment of clinical and mycological success) at End 
of Treatment (EoT).  
10.2 
Secondary Objectives 
 To evaluate the safety and tolerability of SCY-078 
 To evaluate the efficacy of SCY-078 by measuring recurrence of the baseline fungal infection 
42 days after EoT (Week 6 Follow up) 
 To determine the efficacy of SCY-078 by measuring subject survival 42 and 84 days after 
Day 1 (first dose of study drug) 
10.3 
Exploratory Objectives 
 To evaluate the efficacy of SCY-078 as determined by the DMC by assessing additional 
efficacy outcomes at EoT 
 To evaluate the efficacy of SCY-078 as determined by the investigator by assessing select 
efficacy outcomes at EoT 
 To determine the interpretative breakpoint of SCY-078 against C. auris  
 To evaluate the pharmacokinetics (PK) of SCY-078 by population PK analysis (for a subset of 
subjects) 


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11.0 Study Endpoints 
11.1 
Primary Endpoints 
 Efficacy as measured by the percentage of subjects with global success (complete or partial 
global response) at EoT as determined by the DMC 
11.2 
Secondary Endpoints 
Safety and tolerability as measured by: 
 Physical examination, vital signs, 12-lead electrocardiogram (ECG), safety laboratory 
tests, AEs and treatment discontinuations 
 The percentage of subjects with treatment-emergent AEs 
 
Efficacy as measured by: 
 The percentage of subjects with a recurrence of the baseline fungal infection 42 days after 
EoT (Week 6 Follow up) 
 The percentage of subjects surviving 42 and 84 days after Day 1 (first dose of study drug) 
11.3 
Exploratory Endpoints 
 Percentage of subjects with complete global response at EoT, as determined by the DMC 
 Percentage of subjects with partial global response at EoT, as determined by the DMC 
 Percentage of subjects with stable disease at EoT, as determined by the DMC 
 Percentage of subjects with progressive disease at EoT, as determined by the DMC 
 Percentage of subjects with clinical success at EoT, as determined by the investigator 
 Percentage of subjects with mycological success at EoT, as determined by the investigator 
 Percentage of subjects with global success at EoT, as determined by the investigator 
 Analysis of response by minimum inhibitory concentration (MIC) based on CLSI M27-A3 in 
vitro method    
 SCY-078 plasma concentration by population PK analysis (for a subset of subjects) 
 


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12.0 Study Design 
12.1 
Overall Description of the Study 
This is a multicenter, open-label, non-comparator, single-arm study to evaluate the efficacy, safety, 
tolerability and PK (for a subset of subjects) of SCY-078 in male and female subjects ≥18 years 
of age with a documented Candida auris infection.  
Subjects must have a documented candidiasis, including candidemia, caused by Candida auris to 
be considered for enrollment. Subjects are also eligible if they are receiving IV antifungal therapy 
for their C. auris infection and, in the judgment of the investigator, continued IV antifungal therapy 
is not feasible or desirable due to clinical or logistical circumstances. Additionally, subjects must 
be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous 
endoscopic gastrostomy (PEG) tube to be able to participate in the study.  
Subjects must meet all study criteria to be eligible for inclusion. Inclusion of each subject in the 
study must be approved by the Sponsor prior to enrollment. 
The study will be conducted at approximately 10 sites globally, and is planned to enroll and treat 
approximately 30 subjects.  
Eligible subjects will receive an initial oral loading dose of 750 mg of SCY-078 (3 tablets of 250 
mg) BID during the first 2 days of treatment and then subsequent oral doses of 750 mg QD for up 
to 90 days. 
The study will consist of a combined Screening and Treatment Day 1 (Baseline) visit to determine 
subject eligibility and begin study treatment; a Treatment Day 2 visit for PK sampling (only for 
subjects who participate in the PK portion of the study); 2 additional scheduled treatment visits 
(Treatment Days 3 to 5 and Treatment Days 7 to 10) and treatment visits every 14 days thereafter 
(for up to a total of 90 days) to continue study treatment and perform clinical, mycological, 
imaging, serological and safety assessments, and to collect PK samples (only for subjects who 
participate in the PK portion of the study); an EoT visit to assess primary and exploratory efficacy 
outcomes; 1 follow-up (FU) visit 6 weeks after EoT (Week 6 Follow-up) to assess recurrence 
(secondary efficacy endpoint) and safety; and 2 survival visits/contacts to determine survival status 
(alive or deceased). 
Efficacy will be assessed primarily in terms of global success (defined as a complete or partial 
global [clinical and mycological] response) at EoT as determined by the DMC. Secondary efficacy 
assessments will include recurrence (after EoT) and survival. Recurrence will be assessed by 
measuring recurrence of the baseline fungal infection 42 days after EoT (Week 6 FU). Survival 
will be determined on Day 42 and Day 84 (42 and 84 days after the Screening/Treatment Day 1 
visit [first dose of study drug]).  This can be an in-person visit or a phone contact, and will 


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document subject status only (alive or deceased). If subject is deceased, the relationship to the 
fungal infection will be recorded. 
Complete global response, partial global response, stable disease and progressive disease at EoT 
as determined by the DMC will be assessed as exploratory efficacy endpoints.  Global success, 
clinical success and mycological success at EoT as determined by the investigator will also be 
assessed as exploratory efficacy endpoints. 
The following study procedures will be performed to assess treatment outcome: clinical signs and 
symptoms of candidiasis; radiological assessments including esophagoscopy and other imaging 
scans, as applicable (e.g., X-ray, ultrasound, CT and MRI); mycological testing (fungal cultures); 
and serological testing (ß-(1,3)-D glucan). 
PK analyses will be performed for subjects who give their consent to participate in the PK portion 
of the study (the PK Subset). Blood samples will be collected on Treatment Day 2 (one sample 
collected anytime post dosing), Treatment Days 3 to 5 (one sample collected predose on any of 
these days) and Treatment Days 7 to 10 (one sample collected predose on any of these days).  
Subjects will be evaluated for safety throughout the study, including parameters such as physical 
exam, vital signs, 12-lead ECGs, safety laboratory tests (hematology, blood chemistry and 
urinalysis), AEs, treatment discontinuations and concomitant medications. A final safety 
assessment will be conducted at the Week 6 Follow-up visit (6 weeks after the EoT). 
Results from the study will be analyzed against historical SoC-treated subjects, who will be 
selected from literature reviews and other data resources, and be based on the 2015 Infectious 
Diseases Society of America guidelines for the management of candidiasis.15  
 
12.2 
Blinding, Randomization and Stratification 
This is an open-label study. There will be no randomization or stratification for this study.  
Eligible subjects must be approved by the Sponsor for enrollment.  
12.3 
Study Duration 
Each subject is expected to complete the study within approximately 132 days. 
12.4 
Number of Subjects and Centers 
Approximately 10 study centers worldwide are expected to participate in subject enrollment and 
treatment. The study is planned to enroll and treat approximately 30 subjects. 


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13.0 Study Population 
13.1 
Inclusion Criteria 
Subjects must fulfill all of the following criteria to be eligible for study admission:  
1. Subject is a male or female adult ≥18 years of age on the day the study informed consent form 
(ICF) is signed. 
2. Subject has a documented candidiasis, including candidemia, caused by Candida auris. The 
subject is also eligible if he/she is receiving IV antifungal therapy for their C. auris infection 
and, in the judgment of the investigator, long-term IV antifungal therapy is not feasible or 
desirable due to clinical or logistical circumstances.  
A documented candidiasis, including candidemia, caused by Candida auris is defined as the 
recovery of Candida auris by culture of a sample obtained within the last 7 days.  
3. Subject is able to tolerate medication orally or through a nasogastric (NG) tube or 
percutaneous endoscopic gastrostomy (PEG) tube.   
4. Subject is not pregnant and is highly unlikely to become pregnant or to impregnate a partner 
since he/she meets at least one of the following criteria:  
a. 
Subject is a female subject who is not of reproductive potential and is eligible without 
requiring the use of contraception. A female subject who is not of reproductive potential 
is defined as one who: (1) has reached natural menopause (defined as 6 months of 
spontaneous amenorrhea with serum follicle-stimulating hormone levels in the 
postmenopausal range as determined by the local laboratory, or 12 months of spontaneous 
amenorrhea); (2) is 6 weeks´ post-surgical bilateral oophorectomy with or without 
hysterectomy; or (3) has undergone bilateral tubal ligation. Spontaneous amenorrhea does 
not include cases for which there is an underlying disease that causes amenorrhea (i.e., 
anorexia nervosa). 
b. Subject is a male subject who is not of reproductive potential and is eligible without 
requiring the use of contraception. A male subject who is not of reproductive potential is 
defined as one whom has undergone a successful vasectomy. A successful vasectomy is 
defined as (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 
2 years ago with no resultant pregnancy despite sexual activity post vasectomy. 
c. Subject is a male or female subject who is of reproductive potential and agrees to remain 
abstinent or use (or have his/her partner use) 2 acceptable methods of contraception 
starting from the time of consent through 28 days after the completion of study therapy. 
Acceptable methods of birth control are intrauterine device, condom, hormonal 
contraceptives and vasectomy. 


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It is not yet known if the use of SCY-078 reduces the efficacy of hormonal contraception 
(including but not limited to oral, injectable, or implantable methods).  Therefore, 
hormonal contraception should not be used without a second study acceptable method of 
birth control.  
Note: Women of childbearing potential must have a negative serum pregnancy test (β-human 
chorionic gonadotropin [β-hCG]) prior to enrollment (performed by the site’s local 
laboratory). 
5. Subject and/or legal representative is/are able to understand and sign a written ICF, which 
must be obtained prior to treatment and any study-related procedures. 
6. Subject and/or legal representative is able to understand and sign a consent or authorization 
form, which shall permit the use, disclosure and transfer of the subject’s personal health 
information (e.g., in the US, a Health Information Portability and Accountability Act 
Authorization form).  
7. Subject and/or legal representative is able to understand and follow all study-related 
procedures including study drug administration. 
13.2 
Exclusion Criteria 
A subject will be excluded from participation in the study if he or she meets any of the following 
exclusion criteria:  
1. Subject has a fungal disease with central nervous system involvement. 
2. Subject has a fungal disease of the bone and/or joint that is expected to require >90 days of 
study drug treatment. 
3. Subject has an inappropriately controlled fungal infection source (e.g. persistent catheters, 
devices, identified abscess) that is likely the source of the fungal infection. 
4. Subject is hemodynamically unstable and/or requiring vasopressor medication for blood 
pressure support. 
5. Subject has abnormal liver test parameters: AST or ALT >10 x ULN and/or total bilirubin >5 
x ULN.  
Note: Subjects with unconjugated hyperbilirubinemia with diagnosis of Gilbert’s disease are 
not excluded. 
6. Subject has an Apache score >16. 
7. Subject has serum creatinine >3 times from Baseline (Screening/Treatment Day 1) value. 


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8. Subject has a prolonged QTcF interval (Fridericia’s correction: QTc = QT/(RR)0.33) >480 ms 
on the baseline ECG or other abnormalities deemed clinically significant by the investigator 
that would put the subject at unacceptable risk for participation in the study. 
9. Subject requires treatment with the prohibited medications listed in Section 23.1 (Appendix A), 
during the following timeframes: 
a. Select strong time-dependent CYP3A4/5 inhibitors and CYP3A4/5 inducers during the 
14 days prior to enrollment and during study treatment  
b. Select strong and moderate reversible CYP3A4/5 inhibitors during the 48 hours prior to 
enrollment and during study treatment 
c. Select P-gp substrates during the 48 hours prior to enrollment and during study treatment  
10. Subject is pregnant or lactating. 
11. Subject has any other condition or laboratory abnormality that, in the judgment of the 
investigator, would put the subject at unacceptable risk for participation in the study or may 
interfere with the assessments included in the study. 
12. Subject has a known hypersensitivity to SCY-078 or any of the components of the formulation. 
13. Subject has participated in any other investigational study within at least 30 days (or 5.5 half-
lives of the investigational product) before signing the ICF.  
14. Subject has received prior treatment with the study drug in a previous trial. 
15. Subject is an employee of SCYNEXIS, Inc., the investigator or the Contract Research 
Organization (CRO) involved in the study, or is an immediate family member (partner, 
offspring, parent, sibling, or sibling’s offspring) of an employee involved in the study. 
16. Subject or legal representative is unable to provide written informed consent for any reason. 
17. Subject is unlikely to comply with protocol requirements. 
 
13.3 
Discontinuation Criteria 
A subject may be discontinued from the study or study drug for any of the following reasons: 
 Withdrawal of consent; 
 Investigator or Sponsor decision that withdrawal is in the subject’s best interest; 
 Deterioration of the clinical condition or delayed response requiring, in the opinion of the 
investigator, alternative therapy. 
 Occurrence of an AE that, in the opinion of the investigator, warrants discontinuation of 
the subject from the study drug; 
 Pregnancy; 


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 Lost to follow up (every attempt should be made to contact the subject). 
The reason for a subject’s discontinuation of treatment or withdrawal from the study will be clearly 
documented in the source documents and on the electronic case report form (eCRF). All EoT 
procedures should be performed for subjects who discontinue from study treatment before the EoT 
visit.  
13.4 
Replacement of Dropouts 
Subjects who discontinue early from treatment will not be replaced. 
14.0 Study Treatments 
14.1 
Study Treatment Groups 
This is an open-label, single-arm study. All enrolled subjects will receive an initial oral loading 
dose of 750 mg of SCY-078 (3 tablets of 250 mg) BID during the first 2 days of treatment and 
then subsequent oral doses of 750 mg QD for up to 90 days. 
For subjects who are unable to take oral medications, tablets may be crushed and administered 
with approximately 8 oz./240 mL of water via an NG or PEG tube. The tube should be closed at 
least one hour before drug administration and be flushed with approximately 8 oz./240 mL of water 
before and after drug administration. 
Oral treatment may be given on an inpatient or outpatient basis, as needed, and for as long as is 
clinically indicated, at the investigator´s discretion, but in no event for more than a total of 90 days 
of antifungal treatment. 
14.2 
Dietary Requirements 
Oral study drug should be taken with approximately 8 oz./240 mL of water. For subjects on 
continuous feeding via an NG or PEG tube, the drug should be crushed and administered with 
approximately 8 oz./240 mL of water. The tube should be closed at least one hour before drug 
administration and should be flushed with approximately 8 oz./240 mL of water before and after 
drug administration. 
Subjects who are not hospitalized or are hospitalized and then discharged will be instructed to take 
the study medication in the morning upon arising and in the evening, approximately 12 hours apart 
(for Day 1 and Day 2). For Day 3 onwards, subjects will be instructed to take the study medication 
in the morning upon arising only. Subjects must take the study drug with approximately 
8 oz./240 mL of water in all cases. Nutraceuticals and foods that are known CYP3A inhibitors, 


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such as grapefruit juice, blood oranges and mulberry juice should not be consumed during the 
study (see Section 23.1 [Appendix A]). 
14.3 
Study Drugs 
The study drug, SCY-078 250-mg tablets, will be provided by the Sponsor. 
14.3.1 SCY-078 Description 
Study Drug Identifier: 
SCY-078 
Empirical Formula: 
C50H75N5O11 (citrate salt) 
Molecular Weight: 
922.18 (citrate salt) 
Physical Description: 
White to off-white solid 
Chemical Name: 
(1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-
2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-
pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-
dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-
phenanthro[1,2-c]pyran-7-carboxylic acid, citrate salt] 
 
Figure 2 
Chemical Structure of SCY-078 Citrate 
 
14.3.2 Formulation, Packaging and Labelling 
SCY-078 citrate drug product for oral administration will be supplied as a tablet containing 250 mg 
of SCY-078 active ingredient on a free-base basis. In addition to the active ingredient, the tablet 
formulation also contains silicified microcrystalline cellulose, crospovidone, mannitol, colloidal 
silicon dioxide, magnesium stearate (non-bovine) and butylated hydroxyanisole. 


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Study drug supplies will be packaged in bottles. Labels on the bottles of SCY-078 will include the 
following information: 
 Sponsor information 
 Protocol number 
 Protocol visit number 
 Place to write the subject number 
 Route of administration 
 Lot number  
 Product name and potency 
 Contents, e.g. number of tablet count per bottle  
 Storage conditions 
 Name of manufacturer and date of manufacture 
 Caution statement: "Caution: New Drug – Limited by Federal (United States) Law to 
Investigational Use Only” 
14.3.3 Storage and Stability 
The pharmacist or appropriate designee at each clinical research site will be responsible for the 
study drug. For long-term storage at the site, study drug supplies provided in bottles must be kept 
in a secure area (e.g., locked cabinet) and stored at room temperature, between 15°C and 30°C. 
The site will be required to keep a temperature log to establish a record of compliance with these 
storage conditions. All study drug will be kept in a secure cabinet or room with access restricted 
to necessary clinic personnel. 
14.4 
Drug Accountability 
The investigator or designee will inventory and acknowledge receipt of all shipments of the study 
drug. Drug accountability logs will be used to maintain accurate records of receipt, dispensing, 
administration to each subject and return of drug. A study monitor will periodically check the 
supplies of investigational products held by the site to verify accountability of all study drugs. At 
the conclusion of the study, after final drug accountability has been completed by the monitor, all 
unused study drug and all medication containers will be returned to the Sponsor or destroyed on 
site if the site has procedures in place for study drug destruction. 
Drug supplies will be maintained in a secure, limited-access storage area under the recommended 
storage conditions (see Section 14.3.3). 


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The study drug supplied for this study is only for use in subjects properly consented and enrolled 
under this protocol. 
This is an open-label study. A study site designee (e.g. pharmacist, study nurse/coordinator) will: 
 Record the treatment in the appropriate drug accountability log 
 Count the number of tablets per bottle before dispensing to the subject 
 Report and document any study medication issues such as crushed or broken tablets  
o All product quality complaints should be reported to the Sponsor 
 Collect and count the number of tablets remaining at the EoT visit 
 Review subject diary and tablet count, record any unused or remaining drug in the drug 
accountability log and eCRF, and note any discrepancies and reason for discrepancies 
14.5 
Subject Compliance with Study Drug Dosing 
Subjects who are not hospitalized and subjects who are discharged from the hospital will be 
instructed to have the study medication (including empty bottles/units) with them at each visit.  
Compliance will be assessed based on remaining study drug as compared to what should have been 
taken and the subject diary where the subject will enter the details of dosing. Details of treatment 
including any missing dose will be recorded in the eCRF. Sites are encouraged to contact the 
medical monitor or Sponsor for concerns of compliance with the treatment regimen, especially for 
subjects who miss doses due to problems with tolerability. 
15.0 Non-Study Treatments 
15.1 
Prior and Concomitant Medications 
All medications (including prescription and OTC medications, supplements, and herbal products) 
taken from 28 days before Screening/Treatment Day 1 through the EoT will be recorded on the 
eCRF. Only the use of antifungal medications, antibiotics for any reason or medications to treat an 
AE will be recorded after EoT and through the Week 6 Follow-up visit. Start and stop times of 
concomitant medications taken during antifungal therapy will be recorded on the eCRF. Subjects 
will also record any new concomitant medications taken between visits in the subject diary. 
Certain concomitant medications must be administered with caution or close monitoring as 
described in Section 15.2 and Section 15.3. 


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15.2 
Prohibited Medications 
Medications specifically not permitted prior to the study and through the Week-6 Follow-up visit 
include the following: 
 Other investigational drug(s)  
 Other antifungals 
 Select strong CYP3A4/5 inhibitors, select moderate CYP3A4/5 inhibitors, select 
CYP3A4/5 inducers, and select P-gp substrates. 
A detailed list of prohibited medications and timeframes is provided in Section 23.1 (Appendix A). 
15.3 
Medications to be Administered with Caution and Monitored as 
Appropriate 
The following medications must be administered with caution and must be monitored as 
appropriate: 
 Select moderate CYP3A4/5 inhibitors  
 Select CYP3A4 substrates, including but not limited to sirolimus, tacrolimus and warfarin 
 
A detailed list of medications to be administered with caution is provided in Section 23.1 
(Appendix A).  
15.4 
Study Restrictions 
There are no additional study restrictions other than those described in Sections 13.2 (Exclusion 
Criteria), Section 14.2 (Dietary Requirements) and Section 15.2 (Prohibited Medications). 
16.0 Study Procedures 
The following sections provide a description of the individual study procedures to be performed 
during the conduct of the study. Detailed schedules of study assessments are provided in the 
Schedule of Visits and Procedures in Table 1. 
16.1 
Informed Consent 
Every study subject (or the subject´s legal representative) must provide written informed consent 
at Screening/Treatment Day 1, prior to participating in any Screening evaluations or any other 
study activities (see Section 21.3). 


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16.2 
Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed at Screening/Treatment Day 1 (prior to study 
treatment) to ensure that the subject qualifies for the trial. 
16.3 
Subject Enrollment and Assignment of Subject Number 
At Screening/Treatment Day 1, all subjects who have signed an ICF will receive an 8-digit subject 
identification (ID) number (prior to study treatment) that will be composed of a 3-digit study 
number (305) and a 2-digit site number followed by a 3-digit sequentially assigned subject number 
starting at 001. Subject numbers will be sequentially assigned by the database upon entry by the 
site. For instance, if site 01 enters the first subject in the database, the subject ID will be 305-01-
001. The second subject entered in the database will get the subject number 002 as entered by any 
site, so that if site 02 enters the second subject, the subject ID will be 305-02-002. This number 
will be unique to each subject and will be used to identify the subject throughout the study.  
Subjects who are screen failures or who are not eligible for enrolment will be recorded as such in 
the subject screening log. The subject numbers assigned to eligible subjects will be recorded in the 
eCRF. Only one subject number will be assigned to each eligible subject.  
For subjects who signed an ICF (i.e., are assigned a subject number) but were NOT treated because 
they did not meet all of the inclusion/exclusion criteria, the Screening/Treatment Day 1  visit pages 
of the eCRF will be completed. The criteria that were not met for enrolment will be documented 
in the eCRF.  
All eligible subjects must be approved by the Sponsor for enrollment. 
16.4 
Medical History and Demographics 
During the Screening/Treatment Day 1 visit (prior to study treatment), a complete medical history 
for the prior year will be recorded for each subject. The medical history will include previous and 
current medical diagnoses, as well as major surgical procedures. Subject demographics such as 
age, sex, race and ethnicity will also be collected. 
16.5 
General Physical Examination  
A general physical exam will be done at Screening/Treatment Day 1 (prior to study treatment), at 
EoT and at the Week-6 Follow-up visit. The physical examination will include an abbreviated 
assessment of general appearance, skin, eyes, heart, chest and abdomen. 


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16.6 
Vital Signs 
Vital signs, including blood pressure (systolic and diastolic), heart rate, respiratory rate and body 
temperature will be measured at Screening/Treatment Day 1 (prior to study treatment), at EoT and 
at unscheduled visits, if applicable. 
16.7 
Twelve-Lead Electrocardiogram  
A 12-lead ECG will be obtained and evaluated locally by a physician for the presence of 
abnormalities at Screening/Treatment Day 1 (prior to study treatment), at EoT and at unscheduled 
visits, if applicable. 
Heart rate, PR interval, QRS, QT and QTcF values will be recorded in the eCRF. Any clinically 
relevant abnormality will be recorded as AE accordingly and will be followed up to 
resolution/satisfaction. 
16.8 
Pregnancy Test  
A serum pregnancy test will be performed at Screening/Treatment Day 1 (prior to study treatment) 
and at EoT by the local laboratory for all female subjects of childbearing potential.  
16.9 
Targeted Physical Examination, Including Clinical Evaluation of Signs 
and Symptoms of Infection 
A targeted examination of the fungal infection site, including the signs and symptoms of the fungal 
disease, will be conducted at Screening/Treatment Day 1 (prior to study treatment), Treatment 
Days 3 to 5, Treatment Days 7 to 10, every 14 days thereafter up to EoT, at EoT, and at the Week 6 
Follow-up. 
The signs and symptoms of the fungal disease include, but are not limited to, the following: 
o Fever, defined as oral temperature ≥38.3°C (≥101°F) on one occasion or >37.8°C 
(>100°F) on two measurements at least 4 hours apart  
o Clinically significant hypothermia <36°C (<96.8°F) 
o Hypotension (systolic blood pressure <90 mmHg or a >30 mmHg decrease below 
normal baseline) 
o Tachycardia 
Subjects who are discharged from the hospital during SCY-078 therapy will record signs and 
symptoms daily on subject diaries and the signs and symptoms will also be assessed by the site 
staff at the study visits. The site will assess whether the signs and symptoms recorded on the subject 
diary are related to the C. auris infection. 


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16.10 Mycological Testing 
Blood cultures: Two sets of blood cultures will be collected at Screening/Treatment Day 1 (prior 
to study treatment) and repeated daily or every other day until blood cultures are negative for at 
least 48 hours (if it is only possible to obtain 1 set of blood cultures, a reason should be 
documented). Blood should be drawn peripherally [directly from a vein]; however, if this is not 
possible, blood may be drawn from  a central IV catheter. Follow-up cultures will be performed as 
clinically indicated. 
Non-blood cultures: A documented culture positive for C. auris of a sample obtained within the 
last 7 days must be available at Screening/Treatment Day 1 (prior to study treatment). Follow-up 
cultures from subjects who have non-blood Candida auris infections should be performed as 
clinically indicated. 
The study site’s local microbiology laboratory will perform identification and in vitro 
susceptibility testing as per their local standards. The investigator should ensure that all Candida 
auris isolates obtained from all cultures performed during the study period are sent to the central 
microbiology laboratory, as described in the laboratory manual.  
Further evaluation to identify the potential mechanism of resistance may be performed.  Isolates 
may be maintained in a repository for potential future use, for subjects that provide consent for 
future use. 
16.11 Imaging  
Imaging scans (e.g., X-ray, ultrasound, computed tomography, magnetic resonance imaging) 
should be performed for the assessment of infection in subjects with non-blood sites of Candida 
infection. The results of these studies should be documented on the eCRF. 
For subjects with fungal diseases where the assessment of outcome is based on imaging, imaging 
scans must be available at Screening/Treatment Day 1 (prior to study treatment) and performed at 
EoT. Additional  images should be obtained if clinically indicated. 
16.12 Serological Testing 
The following serological examinations will be performed at Screening/Treatment Day 1 (prior to 
study treatment) and at the recommended time points below:  
 Two ß-(1,3)-D-glucan consecutive tests every 72 hours until negative 
16.13 Safety Laboratory Tests  
Safety laboratory tests (hematology, blood chemistry and urinalysis) will be measured at 
Screening/Treatment Day 1 (prior to study treatment), at Treatment Days 7 to 10, every 14 days 


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thereafter up to EoT if clinically indicated, at EoT, at the Week 6 Follow-up if clinically indicated, 
and at unscheduled visits if clinically indicated. These may also be done more frequently as follow 
up to a laboratory abnormality.  
 
The following laboratory parameters will be determined: 
Hematology  
 White blood cell (WBC) count  
 Hemoglobin 
 Red blood cell (RBC) count  
 Hematocrit 
 Platelet count 
 
 Differential WBC count will include percentages for segmented neutrophils, lymphocytes, 
monocytes, eosinophils and basophils, and absolute counts for neutrophils, lymphocytes, 
atypical lymphocytes, monocytes, eosinophils and basophils. 
 
Blood Chemistry 
 Sodium 
 Glucose 
 Potassium 
 Albumin 
 Alkaline Phosphatase 
 Chloride  
 Blood urea nitrogen (BUN) 
 Creatinine 
 Total creatine phosphokinase (CPK) 
 Aspartate aminotransferase (AST/SGOT) 
 Alanine aminotransferase (ALT/SGPT) 
 Gamma glutamyl transferase (GGT) 
 Lactate dehydrogenase (LDH) 
 Bilirubin (total, direct, and indirect) 
 Total protein  
 
Coagulation test 
 Prothrombin time (PT) 
 Activated partial thromboplastin (aPTT) 
 Thrombin time (TT) 
 D-dimer 
  


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Urinalysis 
 Appearance (clarity, color) 
 Glucose  
 Specific gravity 
 Ketones  
 pH 
 Protein  
 Blood 
 Leukocytes  
 Bilirubin  
 Urobilinogen  
 
Reflex Microscopic Evaluation 
 Bacteria 
 Mucous 
 Casts 
 RBC 
 Crystals 
 WBC 
 Epithelial cells 
 
 
16.14 Pharmacokinetic Sample Collection (PK Subset Only) 
PK testing will be conducted for subjects who give their consent to participate in the PK portion 
of the study (the PK Subset). Up to three (3) blood samples will be collected at the following visits 
and sampling windows: Treatment Day 2 (one sample collected anytime post dosing), Treatment 
Days 3 to 5 (one sample collected predose on any of these days) and Treatment Days 7 to 10 (one 
sample collected predose on any of these days).  
On PK sampling days, the investigator must record the dosing times and sample collection times 
on the eCRF and on the subject’s medical record.  
Procedures for collecting, storing, and shipping plasma samples for PK are described in the study 
PK Manual. The sparse samples collected in this study will be analyzed using Population PK (Pop 
PK) analysis methods to estimate PK parameters (Cmax, AUC, clearance/fraction absorbed [CL/F]) 
as applicable. 
Further analysis of possible metabolites may be performed. 
 
16.15 Efficacy Assessment  
Efficacy will be assessed primarily in terms of global success at EoT as determined by the DMC. 
Complete global response, partial global response, stable disease and progressive disease as 
determined by the DMC and global success, clinical success and mycological success as 
determined by the investigator will also be assessed at EoT.  
The following study procedures will be performed to assess treatment outcome: 


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 Clinical signs and symptoms of candidiasis (Section 16.9) 
 Radiological assessments including esophagoscopy and other imaging scans, as applicable 
(e.g., X-ray, ultrasound, CT and MRI) (Section 16.11). 
 Mycological testing (fungal cultures) (Section 16.10.) 
 Serological testing (ß-(1,3)-D glucan) (Section 16.12) 
Efficacy assessments will also include recurrence (after EoT) and survival. Recurrence will be 
assessed by measuring recurrence of the baseline fungal infection 42 days after EoT (Week 6 FU). 
Survival will be determined on Day 42 and Day 84 (42 and 84 days after Screening/Treatment Day 
1 [first dose of study drug]). This can be an in-person visit or a phone contact, and will document 
subject status only (alive or deceased). If subject is deceased, the relationship to the fungal 
infection will be recorded.  
See Section 20.7.1 for a detailed description of efficacy outcomes. 
16.16 Study Drug Dispensing, Collection and Treatment Compliance 
Evaluation 
For subjects who are not hospitalized, the study drug will be dispensed at Screening/Treatment 
Day 1. Subjects who are hospitalized and are later discharged from hospital will be dispensed their 
study drug at the time they are discharged. Study drug will be dispensed at each Treatment visit 
and will be supplied in bottles containing enough study drug to last until the next study visit. Study 
drug will be collected for treatment compliance evaluation on Treatment Days 3 to 5, Treatment 
Days 7 to 10,  every 14 days thereafter up to EoT and at unscheduled visits prior to EoT (see 
Section 14.5 for further details).   
16.17 Study Drug Dosing 
All enrolled subjects will receive an initial oral loading dose of 750 mg of SCY-078 (3 tablets of 
250 mg) BID during the first 2 days of treatment and then subsequent oral doses of 750 mg QD 
for up to 90 days. Oral treatment may be given on an inpatient or outpatient basis, as needed, and 
for as long as is clinically indicated, at the investigator´s discretion, but in no event for more than 
a total of 90 days of antifungal treatment.  
For subjects who are unable to take oral medications, tablets may be crushed and administered 
with approximately 8 oz./240 mL of water via an NG or PEG tube. The tube should be closed at 
least one hour before drug administration and be flushed with approximately 8 oz./240 mL of water 
before and after drug administration. 
Further details of the study treatment and dietary requirements for treatment administration are 
provided in Section 14.1 and Section 14.2, respectively. 


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16.18 Subject Diary Dispensing, Collection and Review 
Non-hospitalized subjects will complete a subject diary up to their EoT visit. The subjects will 
record the date/time of study medication dosing, daily symptoms, other medical concerns or 
complaints and concomitant medications.   
Subject diaries will be dispensed at Screening/Treatment Day 1 and will be reviewed on Treatment 
Days 7 to 10, every 14 days thereafter up to EoT, at EoT and at any unscheduled visit conducted 
prior to EoT. Subject diaries will be collected at EoT.  
16.19 Prior and Concomitant Medication Review 
All medications (including prescription and OTC medications, supplements, and herbal products) 
taken from 28 days before Screening/Treatment Day 1 through the EoT will be recorded on the 
eCRF. Only the use of antifungal medications, antibiotics for any reason or medications to treat an 
AE will be recorded after EoT and through the Week 6 Follow-up visit. See Section 15.0 for 
prohibited medications, medications to be administered with caution and further details for non-
study treatments. 
16.20 Adverse Event Monitoring 
AEs will be collected and evaluated from the time the informed consent is signed through the EoT. 
After the EoT and up to the last observation in the study (Week 6 Follow-up), new AEs will be 
collected only if deemed related to the study drug, if they are serious adverse events (SAEs), or if 
they are related to a fungal infection.  
See Section 18.0 for details regarding safety assessment and monitoring. 


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17.0 Study Schedule 
Detailed schedules of all study visits and procedures are presented in the Schedules of Visits and Procedures (Table 1 and Table 2). 
Table 1: 
Schedule of Treatment Visits and Procedures (Study SCY-078-305)  
PROCEDURE 
Visit 
Visit 1 
Screening/ 
Treatment Day 1 
(Baseline) 
Visit 2 
Treatment Day 2 
(PK Subset only) 
Visit 3 
Treatment 
Days 3 to 5 
Visit 4 
Treatment 
Days 7 to 10 
Visit 5-10 
Every 14 days 
during 
Treatment 
EoT 
Day 
 
Week 6 
Follow-up 
(6 weeks 
after EoT) 
Unscheduled 
Visits/ 
Days (allowable window)  
Day -1 to Day 1 
 
 
 
 
± 2 days 
± 2 days 
± 2 days 
 
Informed Consent 
Xa 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria  
Xa 
 
 
 
 
 
 
 
Subject Enrollment and ID Assignment  
Xa 
 
 
 
 
 
 
 
 Medical History and Demographics 
Xa 
 
 
 
 
 
 
 
General Physical exam 
Xa 
 
 
 
 
X 
X 
 
Vital Signs 
Xa 
 
 
 
 
X 
 
If applic. 
12-Lead ECG 
Xa 
 
 
 
 
X 
 
If applic. 
Pregnancy Test 
Xa 
 
 
 
 
X 
 
 
Targeted Physical Exam including Clinical 
Evaluation of Signs and Symptoms of 
Infection  
Xa 
 
 
X 
X 
X 
X 
X 
 
All Mycological Testing 
Xa 
 
If applic. 
If applic. 
If applic. 
If applic. 
If applic. 
If applic. 
Imaging (if applicable) 
Xa 
 
If applic. 
If applic. 
If applic. 
X 
If applic. 
If applic. 
Serological Testing 
Xa 
 
If applic. 
If applic. 
If applic. 
X 
If applic. 
If applic. 
Clinical Safety Laboratory Assessments 
(hematology, blood chemistry, urinalysis) 
Xa 
 
 
X 
If applic. 
X 
If applic. 
If applic. 
Pharmacokinetic Assessments (PK Subset 
only)b  
 
X 
X 
X 
 
 
 
 
Efficacy Assessment 
 
 
 
 
 
X 
X 
 
Study Drug Dispensing 
X 
 
X 
X 
X 
 
 
 
Study Drug Dosingc 
    X---------------------------------------------------------------------------------------------X 
 
 
Study Drug Collection and Treatment 
Compliance Evaluation 
 
X 
X 
X 
X 
X 
 
X 
Subject Diary Dispensing, Collection and 
Review 
X 
 
 
X 
X 
X 
 
X 
Prior and Concomitant Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Monitoring 
X 
X 
X 
X 
X 
X 
X 
X 


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PROCEDURE 
Visit 
Visit 1 
Screening/ 
Treatment Day 1 
(Baseline) 
Visit 2 
Treatment Day 2 
(PK Subset only) 
Visit 3 
Treatment 
Days 3 to 5 
Visit 4 
Treatment 
Days 7 to 10 
Visit 5-10 
Every 14 days 
during 
Treatment 
EoT 
Day 
 
Week 6 
Follow-up 
(6 weeks 
after EoT) 
Unscheduled 
Visits/ 
Days (allowable window)  
Day -1 to Day 1 
 
 
 
 
± 2 days 
± 2 days 
± 2 days 
 
Abbreviations: AE=adverse event; applic.= applicable; ECG=electrocardiogram; EoT=end of treatment; PK = pharmacokinetic(s). 
a. Conducted prior to first study drug dosing 
b. PK testing will be conducted for subjects who give their consent to participate in the PK portion of the study (the PK Subset). Sparse PK samples for Population PK 
analysis will be collected at the following visits and sampling windows: on Treatment Day 2 (one sample collected anytime post dosing); between Treatment Days 3 
to 5 (one sample collected predose on any of these days) and between Treatment Days 7 to 10 (one sample collected predose).  The time of dosing and sample 
collection must be recorded on the subject diary and eCRF. 
c. All enrolled subjects will receive an initial oral loading dose of 750 mg of SCY-078 (3 tablets of 250 mg) BID during the first 2 days of treatment and then 
subsequent oral doses of 750 mg QD for up to 90 days. 
 
 
Table 2 Schedule of Survival Visits and Procedures (Study 
SCY-078-305) 
PROCEDURE 
Visit 
Visit/contact  
Survival 
Day 42 
Visit/contact  
Survival 
Day 84 
Days (allowable window) 
± 2 
± 2 
Subject Status (alive/ deceased) 
X 
X 
 
 


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18.0 Safety Assessments and Monitoring 
18.1 
Definition of an Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom or disease 
temporally associated with the use of a study drug/study intervention, whether or not 
related to the study drug/study intervention. 
Any laboratory abnormality that is deemed to be clinically significant in the opinion of the 
investigator will be considered an AE and should be recorded in the eCRF, whether or not 
it is related to the study drug. 
Stable chronic conditions that are present prior to clinical trial enrollment and do not 
worsen are not considered AEs and will be accounted for in the subject’s medical history. 
The following can be considered AEs: 
 An exacerbation of a pre-existing illness 
 An increase in frequency or intensity of a pre-existing episodic event or condition 
 A condition detected or diagnosed after the initiation of treatment with study 
medication, even though it may have been present prior to the start of the study 
 Continuous persistent disease or symptoms present at Baseline that worsen after 
signing the informed consent or following the initiation of treatment with study 
medication 
The following are not considered AEs: 
 Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction or 
transfusion); the condition that leads to the procedure is an AE 
 Pre-existing disease or conditions present or detected at the start of the study that 
do not worsen 
 Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalizations for cosmetic surgery or elective surgery or social/convenience 
admissions) 


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 The disease being studied or signs or symptoms associated with the disease, unless 
more severe than expected for the subject’s condition or a worsening of the disease 
being studied 
18.2 
Definition of a Serious Adverse Event 
A SAE is defined as an AE meeting one of the following outcomes: 
 Death 
 Life-threatening event 
 Inpatient hospitalization or prolongation of existing hospitalization 
 Persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions 
 Congenital anomaly or birth defect 
Any other important medical event that may not result in one of the above outcomes may 
be considered a SAE when, based upon appropriate medical judgment, the event may 
jeopardize the participant and may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
A life-threatening AE is any AE that places the subject, in the view of the investigator, at 
immediate risk of death from the AE as it occurred.  It does not include an AE that, had it 
occurred in a more severe form, might have caused death. 
18.3 
Events of Clinical Interest 
The following are considered events of clinical interest (ECIs), and must be reported by 
the site when it becomes aware of the ECI: 
 QTc >500 ms or a >60-ms change from Baseline, confirmed by repeat testing 
 ALT or AST >8 x ULN, if new compared to Baseline, confirmed by repeat testing 
 ALT or AST >5 x ULN for more than 2 weeks and if new compared to Baseline, 
confirmed by repeat testing 
 ALT or AST >3 x ULN and either total bilirubin >2 x ULN or INR >1.5 and if new 
compared to Baseline, confirmed by repeat testing 
 ALT or AST >3 x ULN, confirmed by repeat testing, with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (>5%)] 


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18.4 
Overdose 
This refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively, which is above the maximum recommended dose 
according to the authorized product information.  
An overdose can occur if a subject has taken, accidentally or intentionally, a drug 
administered in a dose exceeding the protocol-specified dose.  An overdose must be 
reported within 24 hours of the site becoming aware of the overdose if such overdose 
occurs with an associated SAE. If an overdose occurs without an associated SAE, the 
overdose must be reported within 5 working days and documented in the subject diary and 
in the subject medical record. 
18.5 
Pregnancy 
Female subjects who become pregnant should be immediately discontinued from the study 
and followed up to determine the outcome of the pregnancy. The pregnancy must be 
reported to the Sponsor within 24 hours of the site becoming aware of the pregnancy.  If 
the pregnancy ends for any reason before the anticipated date, the investigator should notify 
the Sponsor. At the completion of the pregnancy, the investigator will document the 
outcome of the pregnancy. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, 
neonatal death or congenital anomaly), the investigator should follow the procedures for 
reporting an SAE. 
18.6 
Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the IB or is of greater specificity or 
severity than those that have been observed with the particular study drug being tested.  For 
example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis.  Similarly, 
cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater specificity) if the IB listed only cerebral vascular accidents.  "Unexpected," as used 
in this definition, also refers to AEs that are mentioned in the IB as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug but are not 
specifically mentioned as occurring with the particular drug under investigation. 


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18.7 
Grading of Adverse Events 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s 
daily activities and will be classified by the investigator as mild, moderate or severe using 
the following criteria: 
 Mild: Awareness of sign or symptom, but easily tolerated. Not likely to require 
medical attention. 
 Moderate: Discomfort enough to cause some interference with daily activity. May 
require medical intervention. 
 Severe: Intense enough to disrupt daily activities. Likely requires medical 
intervention. 
Clarification of the difference in meaning between “severe” and “serious” 
The term “severe” is often used to describe the intensity (severity) of a specific event (as 
in mild, moderate or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as 
“serious”, which is based on the outcome or action criteria usually associated with events 
that pose a threat to life or functioning. Seriousness (not severity) serves as a guide for 
defining regulatory reporting obligations. 
18.8 
Causality Assessment 
The investigator will assess causality (i.e., whether there is a reasonable possibility that the 
study drug caused the event) for all AEs and SAEs. The relationship will be characterized 
using the following classification: 
 Related: The temporal relationship of the AE with the study drug makes causality 
possible and cannot be due to another cause such as other drugs, a surgical 
intervention or an underlying disease. 
 Not related: The temporal relationship of the AE with the study drug makes 
causality improbable and can be due to another cause such as other drugs, a surgical 
intervention or an underlying disease. 
18.9 
Adverse Event Collection Timeframe 
AEs will be collected and evaluated from the time the informed consent is signed through 
the EoT. After the EoT and up to the last observation in the study, new AEs will be 


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collected only if deemed related to the study drug, if they are SAEs, or if they are related 
to a fungal infection. 
All AEs reported by the subject or observed by members of the clinical staff will be 
evaluated by the principal investigator (PI) or qualified designee. The PI will attempt, if 
possible, to establish a diagnosis based on presenting signs and symptoms. The nature of 
the AE, time of onset relative to study drug administration, duration, severity, and 
relationship to treatment should be determined. Details of any corrective treatment must be 
recorded in the eCRF. The PI will determine whether any changes have occurred in 
baseline signs and symptoms. All AEs and SAEs will be collected in the eCRF. 
18.10 Serious Adverse Event Reporting Requirements 
All SAEs must be reported within 24 hours of the site becoming aware of the SAE. Any 
event that is serious, study drug-related, and unexpected as assessed by the medical monitor 
or the Sponsor will be submitted to the regulatory authorities in accordance with national 
regulatory laws and regulations. The PI will be responsible for reporting all SAEs that 
require reporting to the local Institutional Review Board/Ethics Committee (IRB/EC) in 
accordance with its regulations and guidelines. 
18.11 Adverse Event and Serious Adverse Event Follow-up 
All AEs and SAEs will be followed up to resolution (the subject’s health has returned to 
her baseline status or all variables have returned to normal) or until an outcome is reached, 
stabilization occurs (the investigator does not expect any further improvement or 
worsening of the event) or the event is otherwise explained, regardless of whether the 
subject is still participating in the study. All appropriate therapeutic measures should be 
undertaken and recorded. Where appropriate, medical tests and examinations will be 
performed to document resolution of the event(s). 
18.12 Serious Adverse Event Reporting – Procedures for Investigators 
Initial Reports and Follow-Up SAE Reports:  
To report an SAE, the SAE eCRF form within the Electronic Data Capture (EDC) system 
must be completed. All SAEs, whether or not deemed drug-related or expected, must be 
reported by the investigator or qualified designee within 24 hours of first becoming aware 
of the event. The investigator/qualified designee will enter the required information 
regarding the SAE into the appropriate form, which will automatically result in distribution 
of the information to the appropriate Sponsor contact. 


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18.13 Procedures for Emergency Unblinding 
This is an open-label study.  No procedures for emergency unblinding are needed. 
19.0 Data 
Collection, 
Study 
Monitoring 
and 
Record 
Management 
19.1 
Data Collection and Reporting 
Data for this study will be collected using eCRFs. The investigator and study site staff will 
receive training regarding the completion of the eCRF. Visit-specific data should be 
entered into the eCRF and be ready for review as soon as possible, but no later than 5 days 
after each visit/time point. 
All protocol-required information collected during the study must be entered by the 
investigator or designated representative in the source documents and eCRF. All data entry, 
modification or deletion will be recorded indicating the individual subject, original value, 
the new value, the reason for change, who made the change, and when the change was 
made.  All data changes will be clearly indicated with a means to locate prior values. The 
investigator will maintain a list of individuals who are authorized to enter or correct data 
on the eCRFs. 
The investigator or designated sub-investigator, following review of the data in the eCRF, 
will confirm the validity of each subject’s data by signing the eCRF. 
19.2 
Study Monitoring 
Study progress will be monitored by the Sponsor or its representative as frequently as 
necessary to ensure adequate and accurate data collection, protocol compliance, and study 
conduct in accordance with accepted regulatory requirements. The PI must make all the 
subject data available to the monitor for review during the planned site monitoring visits. 
Arrangements for monitoring visits will be made in advance, except in emergency cases. 
19.3 
Investigator Study Files 
The PI is responsible for maintaining all study-related documents in study files. The 
Sponsor will notify the PI when retention of study files is no longer necessary. The 
following documents will be kept in the study files or be readily accessible: 
 original protocol and all amendments; 
 signed agreement or protocol; 
 signed and dated study staff roles and responsibilities log; 
 copy of the current curriculum vitae of the PI and of all sub-investigators; 


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 IRB/EC membership list and all IRB/EC approvals for the protocol and amendments, 
informed consent documentation and all updates, advertisements, and written 
information provided to subjects; all IRB/EC correspondence; documentation that the 
IB and subsequent revisions have been submitted to the IRB/EC; documentation that 
all SAEs and any periodic safety reports have been submitted to the IRB/EC; and 
annual IRB/EC renewals (as required); 
 updated laboratory certification and the laboratory’s normal values (covering the entire 
time interval of the study for all laboratory tests conducted during the study); 
 all confirmations of investigational drug receipt, drug accountability logs and drug 
return records; 
 a CD or DVD containing final subject eCRF data; 
 all correspondence to or from the Sponsor or its designees; 
 blank informed consent form; 
 Investigator’s Brochure; 
 subject screening log; 
 subject list (contains subject initials and/or protocol-specific subject number); 
 all subjects’ original signed informed consents; and, 
 monitoring visit log. 
19.4 
Retention of Records 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application and until there are no pending or contemplated marketing 
applications, or at least 2 years have elapsed since the formal discontinuation of the clinical 
development of the investigational product.  These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. 
The Sponsor will inform the PI/institution in writing of the need for record retention and 
will notify the PI/institution in writing when the trial-related records are no longer needed. 
An investigator who withdraws from the responsibility of maintaining study records or 
wishes to move them to a new location has the obligation to place them in safekeeping and 
to inform the Sponsor of their location. 
20.0 Analytical Plan 
All statistical processing will be performed using SAS® version 9.3 or later, unless 
otherwise stated.  
Descriptive statistics (i.e., number of subjects, mean, standard deviation, median, 
minimum, maximum) will be presented for all continuous variables; number and 


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percentage of subjects will be presented for categorical variables. For parameters measured 
over time, observed data and changes from baseline will be described for each time point.  
All analyses of the study results for SCY-078 will be descriptive. Unless otherwise stated, 
data will be analyzed as is with no imputation. 
A Statistical Analysis Plan (SAP) describing all statistical analyses in detail will be 
provided as a separate document.  
20.1 
Sample Size Determination 
This is an exploratory study and no formal sample size calculation was performed.  
A total of 30 subjects are estimated to be adequate for an assessment of the safety and 
tolerability of SCY-078 in subjects with candidiasis, including candidemia, caused by C. 
auris. 
20.2 
Analysis Populations 
Intent-to-Treat (ITT) Population: The ITT Population will include all subjects who are 
enrolled in the study. 
Per-Protocol (PP) Population: The PP Population will include all ITT subjects who 
receive at least 10 total days of antifungal therapy (SCY-078), who have an EoT assessment 
and who have no major protocol violations that would impact the assessment of efficacy.  
Safety Population: The Safety Population will include all subjects who receive at least 
one dose of study medication and have at least one safety assessment post baseline. 
PK Population: The PK Population will include all enrolled subjects who provide at least 
one PK sample. 
20.3 
Subject Disposition, Discontinuation, and Baseline Data 
Subject disposition in terms of the number and percentage of subjects enrolled by site will 
be tabulated. The number of subjects enrolled, number completing the study and reasons 
for discontinuation will be summarized. Subject demographics and baseline characteristics 
such as age, race, ethnicity, sex, weight, height, body mass index, country and other 
relevant parameters will be tabulated.  
Baseline is defined as the last non-missing assessment prior to the date (and time if 
appropriate) of the first dose of study drug. Change from baseline is defined as:post-
baseline value – baseline value. 


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20.4 
Handling of Missing Data, Dose Adjustments, and Early 
Withdrawals 
For the efficacy analyses, subjects who do not have an EoT assessment will be assigned as 
treatment failures. For subjects who withdraw from the study early, every effort will be 
made to collect EoT visit information at the point of withdrawal. 
20.5 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization 
Drug Dictionary terminology. The number and percentage of subjects taking each 
medication before and after the first dose of study drug will be tabulated. Medications taken 
and stopped prior to the first dose of study drug will be considered prior medications. 
Medications started on or before the FU visit date with missing stop dates or stop dates 
after the first dose of study drug will be considered concomitant medications.  
20.6 
Pharmacokinetics (PK Subset Only) 
20.6.1 Pharmacokinetic Assessments 
PK testing will be conducted for subjects who give their consent to participate in the PK 
portion of the study (the PK Subset). Up to three (3) blood samples will be collected at the 
following visits and sampling windows: Treatment Day 2 (one sample collected anytime 
post dosing), Treatment Days 3 to 5 (one sample collected predose on any of these days), 
and Treatment Days 7 to 10 (one sample collected predose on any of these days).  
20.6.2 Pharmacokinetic Analyses 
The PK analysis will be conducted on the PK Population. The concentration versus time 
data from the sparse PK samples collected in this study will be analyzed using a Pop PK 
model to estimate Cmax, AUC and CL/F, as applicable. Further analysis of possible 
metabolites may be performed. 


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20.7 
Efficacy 
20.7.1 Efficacy Assessments 
20.7.1.1 
Clinical, Mycological and Global Outcomes 
Efficacy will be assessed primarily in terms of global success (defined as a complete or 
partial global (clinical and mycological) response) at EoT as determined by the DMC. 
Complete global response, partial global response, stable disease and progressive disease 
at EoT as determined by the DMC will be assessed as exploratory endpoints.  Global 
success, clinical success and mycological success at EoT as determined by the investigator 
will also be assessed as exploratory endpoints. 
Global Outcome 
Global outcome will be scored as global success (complete global response or partial global 
response) or global failure (stable disease or progressive disease) 
Global success: Global success is defined as a complete global response or a partial global 
response 
 Complete global response is defined as a complete clinical response (the resolution of 
all clinical signs and symptoms and/or radiological abnormalities from baseline 
attributable to the Candida auris infection) and a mycological response (mycological 
clearance (direct and/or negative cultures [when obtainable] and/or normal serological 
results [when appropriate]) 
 Partial global response is defined as a partial clinical response (major improvement of 
all clinical signs and symptoms and/or radiological abnormalities from baseline 
attributable to the Candida auris infection) and a mycological response (mycological 
clearance (direct and/or negative cultures [when obtainable] and/or normal serological 
results [when appropriate]) 
Global failure: Global failure is defined as either stable disease and/or progressive disease 
 Stable disease is defined as minor or no clinical improvement but without deterioration 
and/or unchanged serological response. 
 Progressive disease is defined as clinical deterioration necessitating alternative 
antifungal therapy or resulting in death, and/or worsened serological response, and/or 
persistence of fungal infection on the basis of culture, microscopic evaluation, or 
histopathological testing. 


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Clinical Outcome 
Clinical success: clinical success is defined as a complete clinical response (the resolution 
of all clinical signs and symptoms and/or radiological abnormalities from baseline 
attributable to the Candida auris infection) or a partial clinical response (major 
improvement of all clinical signs and symptoms and/or radiological abnormalities from 
baseline attributable to the Candida auris infection). 
Mycological Outcome 
Mycological success: mycological success is defined as a mycological response 
(mycological clearance (direct and/or negative cultures [when obtainable] and/or normal 
serological results [when appropriate]). 
 
20.7.1.2 
Recurrence and Survival 
Secondary efficacy assessments will include recurrence (after EoT) and survival.   
Survival: Survival will be determined on Day 42 and Day 84 (42 and 84 days after 
Screening/Treatment Day 1 [first dose of study drug]). This can be an in-person visit or a 
phone contact, and will document subject status only (alive or deceased). If subject is 
deceased, the relationship to the fungal infection will be recorded.  
Recurrence: Recurrence will be assessed by measuring recurrence of the baseline fungal 
infection 42 days after EoT (Week 6 FU). 
Recurrence is defined as global success at EoT but re-emergence of the baseline Candida 
auris infection during the post treatment follow-up.  Re-emergence of the Candida auris 
infection is required to be with the same species and involving the same site that was 
initially identified at Screening/Treatment Day 1. 
20.7.2 Efficacy Analyses 
The primary efficacy endpoint, the percentage of subjects with global success (complete 
or partial global response) as determined by the DMC at EoT, will be presented with a 95% 
confidence interval (CI) for the ITT and PP populations.  
Secondary and exploratory categorical endpoints will be presented with 95% CIs for the 
ITT and PP populations. 
The percentage of subjects surviving at 42 and 84 days after Screening/Treatment Day 1 
(first dose of study drug) will be presented for the ITT and PP populations; Kaplan-Meier 
curves will be presented. 


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20.8 
Safety  
20.8.1 Safety Assessments 
Subjects will be evaluated for safety and tolerability throughout the study, including 
parameters such as physical exam, vital signs, 12-lead ECGs, safety laboratory tests 
(hematology, blood chemistry and urinalysis), concomitant medications, AEs and 
treatment discontinuations.  
Safety procedures are described in Section 16.0 and safety assessments are described in 
Section 18.0. 
 
20.8.2 Safety Analyses 
All safety analyses will be conducted using the safety population; all safety variables will 
be listed. 
The incidence and severity of treatment-emergent AEs and SAEs and their relationship to 
treatment will be summarized.  AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) Version 19.1 or higher and presented by system organ 
class and preferred term.   
Early discontinuation of study drug treatment will be presented and will include the reasons 
for and timing of such discontinuations.  
Prior and concomitant medications will be summarized; medications will be classified 
based on the World Health Organization´s Drug Dictionary terminology. 
Abnormal physical examinations will be listed.  Laboratory evaluations will be 
summarized as observed values and changes from Baseline; shifts with respect to the 
laboratory reference range will be summarized. 
Vital signs and ECG evaluations will be summarized as observed values and changes from 
Baseline. 
 


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21.0 Ethics and Protection of Human Patients 
21.1 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, the ethical principles 
established by the Declaration of Helsinki (as amended in Fortaleza, Brazil, October 2013), 
the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines, the US Code of Federal Regulations (CFR) sections that address clinical 
research studies, applicable European Union regulations and/or other national and local 
ethical and legal requirements, as applicable. 
21.2 
Institutional Review Board/Ethics Committee Review 
The PI must provide the IRB/EC with all appropriate materials, including a copy of the 
subject ICF. The study will not be initiated until the PI obtains written approval of the 
protocol and the subject ICF from the appropriate IRB/EC, and copies of these documents 
are received by the Sponsor. Appropriate reports on the progress of this study will be made 
by the PI to the IRB/EC, medical monitor, and Sponsor in accordance with applicable 
government regulations and in agreement with policy established by the Sponsor. 
21.3 
Informed Consent  
The ICH issued guidelines to provide protection for human subjects in clinical 
investigations. The ICH Tripartite Guideline for Good Clinical Practice establishes the 
general requirements for informed consent. Each subject will be provided with oral and 
written information in a language they can understand that describes the nature and 
duration of the study. Before undergoing screening, each subject must consent in writing 
to study participation. The patient (or the subject’s legal representative) will sign and 
personally date the subject ICF. The person rendering consent will also sign and personally 
date the subject ICF as the person who obtained the consent of the subject. The original 
signed subject ICF will be retained with the study center’s records. Each subject will 
receive a copy of his/her signed subject ICF. In addition, the PI, or his or her designee, 
must document in the case history that informed consent was obtained before study 
participation.  
21.4 
Future Use of Samples 
Biological samples collected during the study, including Candida spp. isolates (see 
Section 16.10) and plasma samples (see Section 16.12 and Section 16.13) may be 


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maintained in repositories for potential future use. Future research of samples and/or 
Candida isolates may include in vitro susceptibility testing of new or existing antifungals 
or analysis of mechanisms of resistance. Future research of plasma samples may include 
analysis of in vitro diagnostics and/or an analysis of SCY-078 metabolites. Future research 
may also include studies that are unknown at this time. The samples will be retained as 
long as deemed useful for the specified research purposes. All samples will be identified 
only by a coded number to maintain subject confidentiality. Researchers requesting 
samples or information from the repository must have a research protocol approved by an 
Institutional Review Board/Ethics Committee. Samples will only be retained for subjects 
that provide consent for future use. 
21.5 
Subject Privacy and Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified only by a coded number to maintain subject privacy and confidentiality. 
All records will be kept in a locked file cabinet. All computer entry and networking 
programs will be performed with coded numbers only. Clinical information will not be 
released without written permission of the subject, except as necessary for monitoring by 
the medical monitor, IRB/EC, the Food and Drug Administration (FDA), the Sponsor or 
where required by law. All local privacy laws must be followed.   
21.6 
 Study Termination 
The PI, the Sponsor, the FDA, and the IRB/EC each reserve the right to terminate the study 
in the interest of subjects’ safety and welfare. The Sponsor reserves the right to terminate 
the study at any time for administrative reasons. 
21.7 
Financial Disclosure 
The financial interests of all investigators from all participating clinical centers must be 
collected prior to study initiation and 1 year following the completion of the clinical trial. 


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22.0 References 
1- Centers for Disease Control and Prevention Internet. Atlanta, GA: Centers for Disease 
Control and Prevention. Fungal Diseases: Invasive Candidiasis Statistics; updated 2016 
Dec 
12; 
cited 
2016 
Dec 
27; 
about 
5 
screens. 
Available 
from: 
http://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html 
2- Farmakiotis D, Kyvernitakis A, Tarrand JJ et al. Early initiation of appropriate treatment 
is associated with increased survival in cancer patients with Candida glabrata fungaemia: 
a potential benefit from infectious disease consultation. Clin Microbiol Infect Internet. 
2015 
cited 
2016 
Dec 
27;21(1):79-86. 
Available 
from: 
http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)00020-2/pdf. 
doi: 10.1016/j.cmi.2014.07.006.  
3- Centers for Disease Control and Prevention Internet. Atlanta, GA: Centers for Disease 
Control and Prevention. Fungal Diseases: Types of Fungal Diseases: Candidiasis. Case 
count 
updated 
2017 
Jul 
14. 
 
Available 
from: 
https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris.html 
4- Larkin E, Hager C, Chandra J et al. The Emerging Candida auris: Characterization of 
Growth Phenotype, Virulence Factors, Antifungal Activity, and Effect of SCY-078, a 
Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation. 
Antimicrob Agents Chemother. 2017. doi 10.1128/AAC.02396-16. 
5- Berkow EL, Angulo D, Lockhart SR. In Vitro Activity of a Novel Glucan Synthase 
Inhibitor, SCY-078, against Clinical Isolates of Candida auris. Antimicrob Agents 
Chemother. 2017; 61(7): e00435-17.  
6- Marcos-Zambrano LJ, Gómez-Perosanz M, Escribano P, Bouza E, Guinea J. The novel 
oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and 
planktonic Candida spp. J Antimicrob Chemother. 2017. doi:10.1093/jac/dkx010. 
7- Pfaller MA, Messer SA, Rhomberg PR, Barroto-Esoda K, Castanheira M. Differential 
Activity of the Oral Glucan Synthase Inhibitor SCY-078 against Wild-Type and 
Echinocandin-Resistant Strains of Candida Species. Antimicrob Agents Chemother. 
2017;61(8):e00161-17. doi: 10.1128/AAC.00161-17. 
8- Perlin DS. Echinocandin Resistance in Candida. Clin Infect Dis. 2015;61(6):S612-17. 
9- Chowdhary A, Sharma C, Meis JF. Candida auris: A rapidly emerging cause of hospital-
acquired 
multidrug-resistant 
fungal 
infections 
globally. 
PLoS 
Pathog. 
2017;13(5):e1006290. https://doi.org/10.1371/journal.ppat.1006290 


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10- Ruiz Gaitán AC, Moret A, López Hontangas JL et al. Nosocomial fungemia by Candida 
auris: First four reported cases in continental Europe. Rev Iberoam Micol. 2017; 34(1):23-
27. 
11- CLSI. 2008a. Reference method for broth dilution antifungal susceptibility testing of 
yeasts; approved standard – third edition. CLSI document M27-A3. Clinical and 
Laboratory Standards Institute, Wayne, PA. 
12- Perfect JR, Marr KA, Walsh TJ et al. Voriconazole Treatment for Less-Common, 
Emerging, or Refractory Fungal Infections. Clin Infect Dis. 2003; 36(9):1122-1131. doi: 
10.1086/374557. 
13- Kuse ER, Chetchotisakd P, da Cunha CA et al. Micafungin versus liposomal 
amphotericin B for candidaemia and invasive candidosis: a phase III randomized double-
blind trial. Lancet. 2007; 369:1519–27. 
14- Odabasi Z, Mattiuzzi G, Estey E et al. β- d -Glucan as a Diagnostic Adjunct for Invasive 
Fungal Infections: Validation, Cutoff Development, and Performance in Patients with 
Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Clin Infect Dis. 2004; 
39(2):199-205. doi: 10.1086/421944. 
15- Pappas PG, Kauffman CA, Andes DR et al. Clinical Practice Guideline for the 
Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. 
Clin Infect Dis Internet. 2016 Feb 15 cited 2016 Dec 27;62(4):e1-50. Available from: 
http://cid.oxfordjournals.org/content/early/2015/12/15/cid.civ933.full.pdf+html. 
doi: 
10.1093/cid/civ933. 
 
 
 


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23.0 Appendices 
23.1 
Appendix A:  Prohibited Medications and Medications to be 
Administered with Caution 
23.1.1 Prohibited Medications 
Investigational Drugs 
No other investigational drugs are allowed during the study from at least 30 days (or 5.5 
half-lives) before signing the informed consent through the Week-6 Follow-up visit. 
 
Antifungals 
No antifungal treatment other than the study drug is allowed during the study.  
 
Other Prohibited Medications 
In addition, the medications listed below are also prohibited. 
 
Strong CYP3A4/5 inhibitors, moderate CYP3A4/5 inhibitors and CYP3A4/5 inducers 
CYP 
Strong Inhibitors 
Moderate Inhibitors 
Inducersa 
3A4/5 
Reversible inhibitorsb 
 boceprevir 
 conivaptan 
 indinavir 
 itraconazolec 
 ketoconazolec 
 lopinavir/ritonavir 
 mibefradil 
 
 nefazodone 
 nelfinavir 
 posaconazolec 
 telaprevir 
 telithromycin 
 voriconazolec 
Reversible inhibitorsb 
 fluconazolec 
 avasimibe 
 carbamazepine 
 phenytoin 
 rifampin 
 St. John’s wort 
Time-dependent 
inhibitorsa 
 clarithromycin 
 ritonavir 
 saquinavir 
 
 


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a. 
The CYP3A4/5 inducers and strong time-dependent CYP3A4/5 inhibitors listed in this table are not 
permitted during the 14 days prior to enrollment and during study treatment. 
b. The strong or moderate reversible CYP3A4/5 inhibitors listed in this table are not permitted during 
the 48 hours prior to enrollment and during study treatment.  
c. 
No antifungal treatment other than the study drug is allowed during the study. 
 
P-glycoprotein (P-gp) substrates 
P-gp Drug Substratesa 
digoxin, colchicine 
a. The P-gp substrates listed in this table are not permitted during the 48 hours prior to 
enrollment and during study treatment. 
 
23.1.2 Medications to be administered with Caution and Monitored as 
Appropriate 
CYP 
Moderate Inhibitors 
3A4/5 
Reversible inhibitors 
 amprenavir 
 aprepitant 
 atazanavir 
 buprenorphine 
 ciprofloxacin 
 crizotinib 
 cyclosporine 
 
 darunavir/ritonavir 
 fosamprenavir 
 imatinib 
 grapefruit juice, blood oranges, mulberry 
juice 
Time-dependent inhibitors:  
 diltiazem 
 erythromycin 
 verapamil 
 


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CYP3A4 substrates 
CYP 
Substrates 
3A4 
In vitro, SCY-078 was an inhibitor of CYP3A mediated metabolism of midazolam, but 
was only a weak inhibitor of metabolism of testosterone. The clinical significance of this 
inhibition is unknown; caution should be exercised when administering SCY-078 with 
drugs known to be CYP3A sensitive substrates with narrow therapeutic index. 
Subjects receiving sirolimus, tacrolimus or warfarin are permitted for enrollment in the 
study and these medications may be administered concomitantly with SCY-078 with 
close monitoring. The administration of either sirolimus or tacrolimus should be offset 
by no less than 2 hours with the administration of SCY-078. At a minimum, blood levels 
of sirolimus, tacrolimus or PT/PTT/INR for subjects on warfarin should be measured 
after the first dose of SCY-078 and when the subject has received approximately 7 days 
of SCY-078 (at which time, SCY-078 concentrations will have reached steady state). 
Dosing adjustments and subsequent monitoring of sirolimus and warfarin should be 
undertaken in accordance with product prescribing information for the respective agents. 
Abbreviations: PT = prothrombin time; PTT = partial thromboplastin time; INR = international 
normalized ratio 
 
Sources: 
 FDA Draft Guidance for Industry.  Drug Interaction Studies – Study Design, Data 
Analysis, and Implications for Dosing and Labeling.  2012. 
 Drug interactions in infectious disease by Stephen C. Piscitelli, Keith Rodvold (2007) 
 UCSF-FDA Transportal 

SAP_001.pdf: 






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TABLE OF CONTENTS 
 
 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 5 
1. 
Introduction........................................................................................................................................ 6 
2. 
Study Objectives ................................................................................................................................ 7 
2.1 
Primary Objectives ........................................................................................................................... 7 
2.2 
Secondary Objectives ....................................................................................................................... 7 
2.2.1 
Secondary Objectives ........................................................................................................... 7 
2.2.2 
Exploratory Objectives......................................................................................................... 7 
2.3 
Study Design .................................................................................................................................... 8 
2.4 
Study Timepoints ........................................................................................................................... 10 
3. 
General Statistical Considerations ................................................................................................... 12 
3.1 
Determination of Sample Size ....................................................................................................... 12 
3.2 
Analysis Populations ...................................................................................................................... 13 
3.3 
General Handling of Missing Data ................................................................................................ 13 
4. 
Subject Disposition .......................................................................................................................... 14 
4.1 
Disposition ..................................................................................................................................... 14 
4.2 
Protocol Deviations ........................................................................................................................ 14 
5. 
Demographics and Baseline Characteristics .................................................................................... 14 
5.1 
Demographics ................................................................................................................................ 14 
5.2 
Medical History .............................................................................................................................. 15 
5.3 
Inclusion and Exclusion Criteria .................................................................................................... 15 
5.4 
Fungal Disease ............................................................................................................................... 15 
5.5 
Enrollment Categories .................................................................................................................... 15 
5.6 
Evidence of Ongoing Infection at Baseline ................................................................................... 15 
6. 
Treatment and Medications ............................................................................................................. 16 
6.1 
Prior and Concomitant Medications............................................................................................... 16 
6.1.1 
Prior Medications ............................................................................................................... 16 
6.1.2 
Concomitant Medications .................................................................................................. 16 
6.2 
Study Treatments ........................................................................................................................... 16 
6.2.1 
Study Participation Calculation and Extent of Exposure ................................................... 16 
6.2.2 
Treatment Compliance ....................................................................................................... 17 
7. 
EFFICACY ...................................................................................................................................... 17 
7.1 
Primary Endpoint ........................................................................................................................... 18 
7.1.1 
Primary Analysis ................................................................................................................ 18 
7.2 
Secondary Endpoints ...................................................................................................................... 19 
7.3 
Exploratory Endpoints ................................................................................................................... 19 
7.3.1 
Exploratory Analyses ......................................................................................................... 19 
7.3.2 
Clinical and Mycological Outcome ................................................................................... 20 
8. 
Safety ............................................................................................................................................... 20 
8.1 
Adverse Events............................................................................................................................... 21 
8.1.1 
Treatment-Emergent Adverse Events ................................................................................ 22 
8.1.2 
Related Adverse Event to Study Treatment ....................................................................... 22 
8.1.3 
Severity of Adverse Event ................................................................................................. 22 
8.1.4 
Adverse Events Leading to Treatment Discontinuation .................................................... 23 
8.1.5 
Death .................................................................................................................................. 23 
8.2 
Clinical Laboratory Evaluations .................................................................................................... 23 
8.2.1 
Pregnancy ........................................................................................................................... 24 
8.3 
Vital Signs ...................................................................................................................................... 24 
8.4 
Physical Examination ..................................................................................................................... 24 
8.5 
12-lead Electrocardiogram ............................................................................................................. 24 
9. 
Interim Analysis and Supplemental Analysis .................................................................................. 24 
10. 
Tables, Listings, and Figures ........................................................................................................... 24 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
 
Abbreviation 
 
 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate transaminase 
BID 
twice a day 
BMI 
body mass index 
CI 
confidence interval 
CRF 
case report form 
CSR 
clinical study report 
DRC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report forms 
e-diary 
electronic diary 
EoT 
end of treatment 
ET 
early termination 
HR 
heart rate 
ITT 
intent-to-treat 
IV 
intravenous 
LOCF 
last observation carried forward 
max 
maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
minimum 
n 
number of subjects 
PK 
pharmacokinetics 
PP 
per protocol 
PT 
preferred term 
QD 
once daily 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOC 
system organ class 
TEAE 
treatment emergent adverse event 
TOC 
test of cure 
WHOCC 
World Health Organization Collaborating Centre  
 
 
 


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1. Introduction 
Candida is among the most common causes of healthcare-associated bloodstream infections in the 
United States (US), with an estimate of 46,000 healthcare-associated Candida infections occurring 
among hospitalized patients in the US each year. The CDC surveillance data have reported that 
approximately 7% of all Candida bloodstream isolates tested are resistant to fluconazole and some 
Candida strains are increasingly resistant to first-line and second-line antifungal treatment agents, 
including azoles and echinocandins.1 Centers specialized in the treatment of immune- 
compromised patients report increased frequency of non-albicans species of Candida with higher 
incidence of resistance. For example, in a survey conducted in the MD Anderson Cancer Center, 
Houston, Texas, US (2005–2013), out of 146 isolates of C. glabrata evaluated, 30 (20.5%) were 
resistant to fluconazole; 15 (10.3%), to caspofungin; and 10 (6.8%), to multiple drugs.2 Roughly, 
30% of patients with drug-resistant Candida bloodstream infections (candidemia) due to drug- 
resistant Candida die during their hospitalization.  
Candida auris is an emerging fungus that presents a serious global health threat. Healthcare 
facilities in several countries have reported that C. auris has caused severe illness in hospitalized 
patients. Some strains of Candida auris are resistant to all three major classes of antifungal drugs. 
This type of multidrug resistance has not been seen before in other species of Candida. Also of 
concern, C. auris can persist on surfaces in healthcare environments and spread between patients 
in healthcare facilities, unlike most other Candida species.3  
SCY-078 (now known as ibrexafungerp) is a member of a new class of antifungal agents and is an 
orally active, semi-synthetic, triterpene derivative of the natural product enfumafungin. 
Ibrexafungerp is a structurally distinct class of glucan synthase inhibitor that inhibits the synthesis 
of the fungal cell wall polymer β-(1,3)-D- glucan. Time-kill studies have demonstrated that 
ibrexafungerp has fungicidal in vitro activity against Candida spp. isolates similar to that observed 
with the echinocandins.  
While three classes of antifungal agents (azoles, echinocandins and polyenes) are currently 
available to treat Candida infections, only azoles are available for oral therapy and rapid 
emergence of resistance on therapy, limits its clinical utility. The emergence of resistance (clinical 
and mycological) to azoles and more recently to echinocandins as well as the toxicity associated 
with polyenes, signals the need for new agents that are well tolerated and retain activity against 
resistant strains. Ibrexafungerp represents the first compound of the triterpene class of β-(1,3)-D-
glucan synthesis inhibitors in development for the treatment of fungal infections. It is structurally 
distinct and retains activity in vitro against both azole-resistant and, importantly, the majority of 
clinical isolates containing FKS gene mutations, which confer echinocandin resistance. Unlike 
echinocandins, ibrexafungerp is orally bioavailable, with in vitro and in vivo activity against 
Candida and Aspergillus species and, as such, it would represent the first oral non-azole treatment 
alternative for these infections. Ibrexafungerp is being developed as the first oral and intravenous 


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(IV) glucan synthase inhibitor for the treatment and prevention of fungal infections caused by 
Candida and Aspergillus species with the potential to provide the therapeutic advantages of both 
an IV and oral formulation. 
This study is being conducted to evaluate the efficacy, safety, tolerability and PK (for a subset of 
subjects) of ibrexafungerp in male and female subjects >18 years of age with a documented 
Candida auris infection. Due to the COVID pandemic causing major delays with shipping of 
samples to the testing laboratory, PK samples could not be analysed within the required testing 
window, and PK analysis is therefore not described in the statistical analysis plan (SAP). 
The purpose of this SAP is to ensure the statistical methodologies that will be used are complete 
and appropriate to allow valid conclusions regarding the study objectives. Results obtained from 
the analyses outlined in this document will be the basis of the final clinical study report (CSR) 
for this protocol. Changes made to the SAP after it has been signed but prior to database lock 
will be documented in a SAP amendment. Changes made to the analyses after database lock will 
be described in the CSR. Additional exploratory analyses which aren’t listed in the protocol are 
planned as outlined in Section 7.3.1. Table shells and data set specifications will be prepared on 
the basis of this document. 
2. Study Objectives 
2.1 Primary Objectives 
The primary objective is to evaluate the efficacy of ibrexafungerp as determined by a Data 
Review Committee (DRC) by assessing global success (composite assessment of clinical and 
mycological success) at End of Treatment (EoT). 
 
2.2 Secondary Objectives 
 
2.2.1 Secondary Objectives 
• To evaluate the safety and tolerability of ibrexafungerp 
• To evaluate the efficacy of ibrexafungerp by measuring recurrence of the baseline fungal 
infection 42 days after EoT (Week 6 Follow up)  
• To determine the efficacy of ibrexafungerp by measuring subject survival 42 and 84 days 
after Day 1 (first dose of study drug) 
 
2.2.2 Exploratory Objectives 
• To evaluate the efficacy of ibrexafungerp as determined by the DRC by assessing 
additional efficacy outcomes at EoT 


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• To evaluate the efficacy of ibrexafungerp as determined by the investigator by assessing 
select efficacy outcomes at EoT  
• To determine the interpretative breakpoint of ibrexafungerp against C. auris  
2.3 Study Design  
This is a multicenter, open-label, non-comparator, single-arm study to evaluate the efficacy, 
safety, tolerability and PK (for a subset of subjects) of ibrexafungerp in male and female subjects 
≥18 years of age with a documented Candida auris infection.  
Subjects must have a documented candidiasis, including candidemia, caused by Candida auris to 
be considered for enrollment. Subjects are also eligible if they are receiving IV antifungal 
therapy for their C. auris infection and, in the judgment of the investigator, continued IV 
antifungal therapy is not feasible or desirable due to clinical or logistical circumstances. 
Additionally, subjects must be able to tolerate medication orally or through a nasogastric (NG) 
tube or percutaneous endoscopic gastrostomy (PEG) tube to be able to participate in the study. 
Subjects must meet all study criteria to be eligible for inclusion. Inclusion of each subject in the 
study must be approved by the Sponsor prior to enrollment.  
The study will be conducted at approximately 10 sites globally, and is planned to enroll and treat 
approximately 30 subjects.  
 
Study Schedule 
The study will consist of a combined Screening and Treatment Day 1 (Baseline) visit to 
determine subject eligibility and begin study treatment; a Treatment Day 2 visit for PK sampling 
(only for subjects who participate in the PK portion of the study); 2 additional scheduled 
treatment visits (Treatment Days 3 to 5 and Treatment Days 7 to 10) and treatment visits every 
14 days thereafter (for up to a total of 90 days) to continue study treatment and perform clinical, 
mycological, imaging, serological and safety assessments, and to collect PK samples (only for 
subjects who participate in the PK portion of the study); an EoT visit to assess primary and 
exploratory efficacy outcomes; 1 follow-up (FU) visit 6 weeks after EoT (Week 6 Follow-up) to 
assess recurrence (secondary efficacy endpoint) and safety; and 2 survival visits/contacts to 
determine survival status (alive or deceased).  
 
Study Treatments 
This is an open-label, single-arm study. All enrolled subjects will receive an initial oral loading 
dose of 750 mg of ibrexafungerp (3 tablets of 250 mg) BID during the first 2 days of treatment 


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and then subsequent oral doses of 750 mg QD for up to 90 days.  
For subjects who are unable to take oral medications, tablets may be crushed and administered 
with approximately 8 oz./240 mL of water via an NG or PEG tube. The tube should be closed at 
least one hour before drug administration and be flushed with approximately 8 oz./240 mL of 
water before and after drug administration.  
Oral treatment may be given on an inpatient or outpatient basis, as needed, and for as long as is 
clinically indicated, at the investigator ́s discretion, but in no event for more than a total of 90 
days of antifungal treatment. 
 
 






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3. General Statistical Considerations 
Continuous data will be described using descriptive statistics (i.e. number of subjects, mean, 
standard deviation (SD), median, minimum, and maximum). Categorical data will be described 
using the subject count and percentage in each category. For the summary statistics of all numerical 
variables unless otherwise specified, minimum and maximum will be displayed to the same level 
of precision as reported. Mean and median will be displayed to one level of precision greater than 
the data collected. Standard deviation / standard error will be displayed to two levels of precision 
greater than the data collected. P-values will be rounded to three decimal places. If a p-value is 
less than 0.001 it will be reported as “<0.001.” If a p-value is greater than 0.999 it will be reported 
as “>0.999.” Data will be displayed in all listings sorted by disease category. 
Unless otherwise specified, baseline will be defined as the last non-missing assessment prior to or 
on the date (and time if appropriate) of the first dose of study drug. Change from baseline is defined 
as: post-baseline value – baseline value. For parameters measured over time, observed data and 
changes from baseline will be described for each time point. 
The study day will be calculated as follows: 
If the assessment date occurs on or after the date of the first dose of study drug: 
Study day = assessment date – first dose date + 1. 
If the date of interest occurs before the date of the first dose of study drug: 
Study day = assessment date – first dose date 
There is no study day 0. 
All analyses will be conducted using SAS® Version 9.4 or higher. All statistical tests will be 
two-sided and interpreted at a 5% significance level. 
 
3.1 Determination of Sample Size 
This is an exploratory study and no formal sample size calculation was performed. 
Approximately 10 study centers worldwide are expected to participate in subject enrollment and 
treatment. The study is planned to enroll and treat approximately 30 subjects.  
 


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3.2 Analysis Populations 
The analysis populations to be used in the analysis are defined as follows: 
Intent-to-Treat Population: The intent-to-treat (ITT) population will include all subjects who are 
enrolled in the study. 
Per-Protocol Population: The per-protocol (PP) population will include all ITT subjects who 
receive at least 10 total days of antifungal therapy (ibrexafungerp), who have an EoT assessment 
and who have no major protocol violations that would impact the assessment of efficacy. 
Safety Population: The safety population will include all subjects who receive at least one dose 
of study medication and have at least one safety assessment post Baseline. 
Pharmacokinetic (PK) Population: There will be no PK population since no PK analysis were 
conducted during the study.  
 
3.3 General Handling of Missing Data 
For incomplete dates related to concomitant medications, the dates will be imputed as follows:  
If the incomplete date is a start/onset date:  
(1) if the month and year are present, then the first day of the month will be used for day.  
(2) if only the year is present, then the first day of January will be used for month and day. 
If the incomplete date is an end date:  
(1) if the month and year are present, then the last day of the month will be used for day.  
(2) if only the year is present, then the last day of December will be used for month and day. If 
the reported year is the same as the informed consent year, then the informed consent date will 
be used.  
Dates that are completely missing will not be imputed. 
Baseline values that are missing will not be imputed. Subjects who have missing subgroup 
values will not be included in that particular subgroup analyses. 
If efficacy data are missing and the subject has not been deemed a success or failure the outcome 
will be categorized as unknown. 


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4. Subject Disposition 
4.1 Disposition 
Subject disposition in terms of the number and percentage of subjects enrolled by site will be 
tabulated. The number of subjects enrolled, number completing the study and reasons for 
discontinuation will be summarized. 
The reason for study discontinuation may include any of the following: adverse event; death; 
disease relapse; progressive disease; lost to follow-up; physician decision; pregnancy; 
withdrawal by subject; other.  
Subject disposition data will be presented in a listing. 
4.2 Protocol Deviations 
The investigator may not deviate from the protocol without a formal protocol amendment having 
been established and approved by an appropriate IRB, except when necessary to eliminate 
immediate hazards to the subject or when the change(s) involve(s) only logistical or 
administrative aspects of the study. 
Major protocol deviations will be defined in the significant protocol deviations rules document. 
Each significant deviation will be assigned a rule number. As the study is ongoing, additional 
significant protocol deviations can also be spontaneously identified or defined by the sponsor 
and/or the project team during the regularly planned study deviation review meetings and the 
significant protocol deviations rules document can be updated. 
All protocol deviations will be reviewed and assessed as to significance prior to the database 
lock. The list of protocol deviations (major or minor) that are additionally considered major 
clinically relevant for the purposes of analysis will also be identified and documented prior to the 
database lock. 
All major protocol deviations will be summarized for all enrolled subjects. Major protocol 
deviations will also be presented in a listing. 
 
5. Demographics and Baseline Characteristics 
5.1 Demographics 
Demographics such as age, sex, race, ethnicity, weight, height, BMI, and country will be 
summarized descriptively for the ITT Population. The age collected in CRF will be used for 


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analysis if it is non-missing. If the age is not collected in the CRF, the age in years is calculated 
using the date of the informed consent and date of birth.  
 
Age (years) = [(Informed Consent Date – Date of Birth + 1) / 365.25]. 
 
BMI is calculated as: 
 
BMI = (body weight in kilograms) / (height in meters)2. 
 
Demographics for all subjects in the ITT set will be presented in a listing. 
5.2 Medical History 
Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
version 26.0 and listed by System Organ Class (SOC), Preferred Term (PT), and verbatim term. 
Medical history will also be summarized by disease group using frequencies and percentages 
with SOCs sorted in alphabetical order and PTs within each SOC in descending order of 
frequency for all subjects in the ITT population. 
A by-subject listing of medical history will be provided. 
5.3 Inclusion and Exclusion Criteria 
Prior to enrollment, the investigator will assess if the subject fulfills all of the inclusion and none 
of the exclusion criteria outlined in the protocol (sections 11.1 and 11.2). The specific inclusion 
criterion not met or exclusion criterion which was met will be recorded in the eCRF. This 
information and whether the sponsor granted a waiver will be presented in a listing. 
5.4 Fungal Disease 
The fungal disease and site of infection, as confirmed by the DRC, will be presented in a listing. 
5.5 Enrollment Categories 
The enrollment categories, as confirmed by the DRC, will be presented in a listing. 
5.6 Evidence of Ongoing Infection at Baseline 
The evidence of ongoing infection at Baseline, as confirmed by the DRC, will be summarized in 
a table and presented in a listing. 


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6. Treatment and Medications 
6.1 Prior and Concomitant Medications 
All medications (including prescription and over-the-counter medications, supplements, and 
herbal products) taken from 28 days before Baseline/Day 1 through EoT will be recorded on the 
eCRF. Only the use of antifungal medications, antibiotics for any reason or medications to treat 
an AE will be recorded after EoT and through the Week 6 Follow-up visit. Start and stop times 
of concomitant medications taken during antifungal therapy will be recorded on the eCRF. 
Subjects will also record any new concomitant medications taken between visits in the subject 
diary. 
All prior and concomitant medications will be coded using the web-based version of the World 
Health Organization Collaborating Centre (WHOCC) ATC/DDD Index 2023 and summarized 
based on the ITT population. A by-subject listing of prior and concomitant medications will be 
provided. 
6.1.1 Prior Medications 
Prior medications are defined as medications taken and stopped prior to the first dose of study 
drug. The number and percentage of subjects who took prior medications will be presented by 
WHO therapeutic drug class and generic drug name. 
6.1.2 Concomitant Medications 
Concomitant medications are defined as medications that are ongoing at or started after the first 
dose of study drug and started on or before the FU visit date, regardless of whether the stop date 
is missing. Medications with a stop date after the first dose of study drug are also considered 
concomitant medications. Medications with incomplete or missing dates will be handled as 
detailed in Section 3.3. A summary showing the number and percentage of subjects who took 
concomitant medications will be presented by WHO therapeutic drug class and generic drug 
name. 
6.2 Study Treatments 
Please refer to Section 2.3 for the details of the study treatment. Data related to the study 
treatment will be presented in a listing. 
6.2.1 Study Participation Calculation and Extent of Exposure 
The duration of study participation (days) is calculated as date of Study Completion/Termination 
recorded on the End of Study page – first dose date + 1. If the date of Study 


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Completion/Termination on the End of Study page is missing, or if a subject is lost to follow-up, 
the latest available visit date will be used.  
The duration of study treatment (days) is calculated as last dose date – first dose date + 1. 
The cumulative doses taken across the treatment period will use the exposure and missed dose 
log. All enrolled subjects will receive an initial oral loading dose of 750 mg of ibrexafungerp (3 
tablets of 250 mg) BID during the first 2 days of treatment and then subsequent oral doses of 750 
mg QD for up to 90 days. The missed dose log will be used to subtract the total number of 
missed doses from these total cumulative doses. 
The duration of study participation, duration of study treatment, and the cumulative doses will be 
summarized by summary statistics. All this exposure information will be presented in a listing. 
6.2.2 Treatment Compliance 
Treatment compliance is defined as the ratio of total study dose to the planned dose, in terms of 
percentage. Treatment compliance will be summarized descriptively. 
Treatment compliance = the cumulative dose / the planned dose *100%. The planned dose is 
defined as 2 doses for the first 2 days and then 1 dose for up to 90 days.  
The treatment compliance will be classified as 0, 25%, 50%, 75%, and ≥100%. This categorical 
data will be summarized with the frequency and percentage of subjects. 
7. EFFICACY  
The primary efficacy and secondary efficacy endpoints will be performed on the ITT and PP 
populations. The ITT analyses will be considered primary and the PP analysis will be considered 
supportive of the primary analyses on the ITT population.  
The primary efficacy endpoint of the study is the percentage of subjects who achieve Global 
Success at EOT, as determined by the DRC. Secondary efficacy endpoints include the 
percentage of subjects with a recurrence of the baseline fungal infection 42 days after EoT 
(Week 6 Follow up) as determined by the DRC, and the percentage of subjects surviving 42 and 
84 days after Day 1 (first dose of study drug).  
Efficacy outcomes will be based on definitions captured in Table 3. Criteria for the Investigator 
is outlined in Section 7.3. 
Additional efficacy endpoints to be evaluated are in Section 7.3. 
 


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7.1 Primary Endpoint 
The primary efficacy objective is to evaluate the efficacy of ibrexafungerp as determined by a 
DRC by assessing global success (composite assessment of clinical and mycological success) at 
EoT. The primary efficacy endpoint of the study is the percentage of subjects with global success 
(complete or partial global response) at EoT as determined by the DRC. Global outcome will be 
scored as global success (complete global response or partial global response) or global failure 
(stable disease or progressive disease) or Unable to determine – due to missing data. 
 
Table 3 
Global Outcome  
Global Response 
Outcome Criteria 
Success 
Complete Global Response: Complete clinical response (the 
resolution of all clinical signs and symptoms and/or radiological 
abnormalities from baseline attributable to the Candida auris 
infection) and a mycological response (mycological clearance 
(direct and/or negative cultures [when obtainable] and/or normal 
serological results [when appropriate]) 
Partial Global Response: Partial clinical response (major 
improvement of all clinical signs and symptoms and/or 
radiological abnormalities from baseline attributable to the 
Candida auris infection) and a mycological response 
(mycological clearance (direct and/or negative cultures [when 
obtainable] and/or normal serological results [when appropriate]) 
Failure 
Stable Disease: Minor or no clinical improvement but without 
deterioration and/or unchanged serological response. 
 
Progressive Disease: Clinical deterioration necessitating 
alternative antifungal therapy or resulting in death, and/or 
worsened serological response, and/or persistence of fungal 
infection on the basis of culture, microscopic evaluation, or 
histopathological testing. 
aNot Evaluable 
Outcome cannot be assessed due to missing data 
 
aCategory added for non-evaluable subjects due to missing data 
 
7.1.1 Primary Analysis 
The primary efficacy analysis will be performed at EoT. A responder analysis will be performed 
on the number and percentage of subjects with Successful Global Response as determined by the 
DRC will be presented with a 95% confidence interval (CI) for a single binomial proportion in 
the ITT and PP populations. The Clopper Pearson method will be used for the confidence 
interval. 
 


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If Global Response has not been deemed a success or failure, the outcome will be categorized as 
not evaluable. A responder is defined as a subject with either a success or a failure. A response of 
not evaluable will not be included in the analysis. 
 
7.2 Secondary Endpoints 
Secondary efficacy assessment includes recurrence (after EoT) and survival. 
The percentage of subjects with a recurrence of the baseline fungal infection 42 days after EoT 
(Week 6 Follow up) as determined by the DRC will be presented with 95% CIs for the ITT and 
PP populations using the same approach as for the primary endpoint. Recurrence is defined as 
global success at EoT but re-emergence of the baseline Candida auris infection during the post 
treatment follow-up. Re-emergence of the Candida auris infection is required to be with the 
same species and involving the same site that was initially identified at Screening/Treatment 
Day 1. 
The percentage of subjects surviving at the defined time points will be presented for the ITT and 
PP populations. A Kaplan Meier plot will also be produced summarizing the survival curve over 
time and the median time to death. A subject without a reported death will be censored at the 
point of last time the subject was known to be alive. The probability of survival will be 
calculated at 42 and 84 days after Day 1 (first dose of study drug). 
 
7.3 Exploratory Endpoints 
Exploratory categorical endpoints will be presented with 95% CIs for the ITT and PP 
populations using the same approach as for the primary endpoint. 
 
7.3.1 Exploratory Analyses 
A responder analysis will be performed on the following endpoints. If the outcome cannot be 
assessed due to missing data, it will be categorized as not evaluable. A responder is defined as a 
subject with a response other than not evaluable. A response of not evaluable will not be included 
in the analysis. 
• Percentage of subjects for each global response (complete response, partial response, stable 
disease, progressive disease) EoT, as determined by the DRC 
• Percentage of subjects with clinical success at EoT, as determined by the investigator and DRC 
• Percentage of subjects for each clinical response (complete response, partial response, stable 
response, progression of fungal disease, death) at EoT, as determined by the DRC 


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• Percentage of subjects with mycological success at EoT, as determined by the investigator and 
DRC 
• Percentage of subjects with global success at EoT, as determined by the investigator 
Additional exploratory analyses: 
• All cause mortality at Day 30 
• Analysis of response by minimum inhibitory concentration (MIC) based on CLSI M27-A3 in 
vitro method and EUCAST method at Screening 
The following exploratory analyses were not originally included in the protocol: 
• Evidence of ongoing infection at Baseline as determined by the DRC 
• Causal relationship of death in the opinion of the DRC (if death is reported at any time during 
the study) 
• Global response by site of infection (candidemia only, Pleural/Pulmonary, Intra-
abdominal/Pelvic, Soft tissue/wound, Bone and joint, Urinary tract, other) 
• Global response by reason for enrollment (primary, refractory, intolerance to SOC, stepdown) 
• Global response by region (India, Pakistan, South Africa) 
• Global response by Age (,65; >= 65 years) 
• Global response by neutropenia (ANC < 500) vs non neutropenic  
7.3.2 Clinical and Mycological Outcome 
Clinical success is defined as a complete clinical response (the resolution of all clinical signs and 
symptoms and/or radiological abnormalities from baseline attributable to the Candida auris 
infection) or a partial clinical response (major improvement of all clinical signs and symptoms 
and/or radiological abnormalities from baseline attributable to the Candida auris infection). 
Mycological success is defined as a mycological response (mycological clearance (direct and/or 
negative cultures [when obtainable] and/or normal serological results [when appropriate]). 
8. Safety 
The safety analyses will be performed on all subjects in the safety population. Analyses will be 
based on physical exam, vital signs, 12-lead ECGs, safety laboratory tests (hematology, blood 
chemistry and urinalysis), concomitant medications, AEs and treatment discontinuations. Safety 
analyses in general will be descriptive and will be presented in tabular format with the 
appropriate summary statistics. 


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Individual subject listings will be provided to support the tables. 
8.1 Adverse Events 
All AE summaries will be restricted to treatment-emergent AEs (TEAEs) only. A TEAE is 
defined as any event not present before exposure to study drug or any event already present that 
worsens in either intensity or frequency after exposure to study drug. 
For the purpose of inclusion in TEAE tables, incomplete AE start and end dates will be imputed 
as follows: 
Missing onset dates (where UK and UNK indicate unknown or missing day and month 
respectively): 
• 
UK-MMM-YYYY: If the month and year are different from the month and year of the 
date of first dose, assume 01-MMM-YYYY. If the month and year are the same as the 
month and year for the date of first dose, and the end date (after any imputation) is on or 
after the date of first dose, then assume the date of first dose. If the month and year are 
the same as the date of first dose, and the end date (after any imputation) is prior to the 
date of first dose, then assume the end date for the start date.  
• 
DD-UNK-YYYY/UK-UNK-YYYY: If the year is different from the year of the date of 
first dose, assume 01-JAN-YYYY of the collected year. If the year is the same as the 
date of first dose year, and the end date (after any imputation) is on or after the date of 
first dose, then assume the date of first dose. If the year is the same as the date of first 
dose, and the end date (after any imputation) is prior to the date of first dose, then 
assume the end date for the start date.  
 
Missing end dates (where UK and UNK indicate unknown or missing day and month 
respectively):  
• 
UK-MMM-YYYY: Assume the last day of the month; 
• 
DD-UNK-YYYY/UK-UNK-YYYY: Assume 31-DEC-YYYY. 
 
All adverse events will be classified by SOC and PT according to the Medical Dictionary for 
Regulatory Activities (MedDRA, March 2023 Version). An overview summary of the number 
and percentage of subjects with any TEAE, serious TEAE, treatment-related TEAE, treatment-
related serious TEAE, TEAE leading to study treatment discontinuation, TEAE leading to study 
discontinuation, and AE leading to death will be provided. 
All AEs will be presented in a listing. 


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8.1.1 Treatment-Emergent Adverse Events 
Summaries of the total number of TEAEs and the number and percentage of subjects with at 
least one TEAE will be provided. Treatment-emergent AEs will be presented by SOC and PT. At 
each level of subject summarization, a subject is counted once if the subject reported one or more 
events. Percentages will be calculated out of the number of subjects in the safety population. 
The summary of TEAEs will be presented in alphabetical order of SOC. Within each SOC, PTs 
will be sorted in descending order from the PT with the highest total to the PT with the lowest 
total frequency. If the total frequency for any two or more PTs is equal, the PTs will be presented 
in alphabetical order. 
The summarization described above will also be repeated for the following: 
• 
Serious Adverse Events; 
• 
Treatment-Related Adverse Events; 
• 
Treatment-Related Serious Adverse Events; 
• 
Adverse Events Leading to Dose Interruption. 
 
8.1.2 Related Adverse Event to Study Treatment 
A summary of related TEAEs to study treatment will be presented in a table. The investigator 
will provide an assessment of the relationship of the event to the study treatment. Related AEs 
are those reported as “Possibly Related”, “Probably Related”, or “Related”. If a subject reports 
multiple occurrences of the same TEAE, only the most closely related occurrence will be 
presented. Treatment-emergent AEs that are missing a relationship will be considered “Related” 
and be presented in the summary table but will be presented in the data listing with a missing 
relationship. Percentages will be calculated based on the number of subjects in the safety 
population. 
The TEAE data will be categorized and presented by SOC and PT in a manner similar to that 
described in Section 8.1.1. 
Related treatment-emergent SAEs to study treatment will also be presented in a table. Treatment-
emergent SAEs that are missing a relationship will be presented in the table as “Related” but will 
be presented in the data listing with a missing relationship. 
 
8.1.3 Severity of Adverse Event 
A summary of TEAEs by severity will be presented in a table. The severity that will be presented 
represents the most extreme severity captured on the CRF page. The possible severities are 
“Mild”, “Moderate”, and “Severe”. 


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In the TEAE severity table, if a subject reported multiple occurrences of the same TEAE, only 
the most severe will be presented. Percentages will be calculated out of the number of subjects in 
the safety population. 
The TEAE data will be categorized and presented by SOC, PT, and severity in a manner similar 
to that described in Section 8.1.1. 
Additionally, the related TEAE data will be categorized and presented by SOC, PT, and severity. 
If a subject reported multiple occurrences of the same related TEAE, only the most severe will 
be presented. Percentages will be calculated out of the number of subjects in the safety 
population. 
Treatment-emergent SAEs by severity will also be presented in a table. 
8.1.4 Adverse Events Leading to Treatment Discontinuation 
A summary of the TEAEs with an action taken with study treatment of “Drug Withdrawn” will 
be presented in a manner similar to that described in Section 8.1.1. 
Any TEAEs leading to treatment discontinuation will be presented in a listing for all subjects. 
8.1.5 Death 
All subjects who have an AE with an outcome of “Death Related to Adverse Event” will be 
presented in a listing. 
8.2 Clinical Laboratory Evaluations 
Summary tables will be presented for clinical laboratory test results (hematology, blood 
chemistry, and urinalysis) at collection visits for subjects in the safety population. Samples for 
clinical laboratory tests will be collected at Screening, Days 7 to 10, every 14 days up to EoT if 
clinically indicated, at EoT, at the 6-Week FU if clinically indicated, and at unscheduled visits if 
clinically indicated. If indicated, these may be done more frequently as follow-up to a laboratory 
abnormality. 
All relevant clinical laboratory tests in chemistry, hematology, and urinalysis will be classified as 
Low, Normal, and High according to the normal ranges. This categorical data will be 
summarized in shift tables comparing the extreme results at each visit with those at the baseline 
visit. Extreme post-baseline results will also be summarized as described in Section 8.2.2. When 
there are multiple values within a visit for a particular laboratory variable, the worst value will be 
taken (worst being the smallest value for criteria below a certain threshold or the largest value for 
criteria above a certain threshold). If a subject has a value below the threshold and above the 
threshold, the value furthest from the threshold will be chosen. 


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In data listings, laboratory values will be compared to normal ranges; out-of-range and clinically 
significant laboratory values will be identified. 
8.2.1 Pregnancy 
Female subjects of child-bearing potential will have urine pregnancy tests conducted at screening 
and at any timepoints during the study, if needed. Only subjects with negative pregnancy test 
results will be enrolled. Any subjects with positive pregnancy test results at any time during the 
study will be presented in a listing. 
8.3 Vital Signs 
Summary tables will be presented for vital sign data, including systolic blood pressure (mmHg), 
diastolic blood pressure (mmHg), body temperature (C), respiratory rate (bpm), and pulse rate 
(bpm) for subjects in the safety population. Observed results at the scheduled visits and changes 
from baseline to post-baseline visits will be presented. All vital sign data by subject will be 
presented in a listing. 
8.4 Physical Examination 
A general physical examination will be conducted at Screening, EoT, and at the 6-Week FU 
visits. The physical examination will include an abbreviated assessment of general appearance, 
skin, eyes, heart, chest, and abdomen. 
All abbreviated physical examinations will be classified as Normal, and Abnormal. Any 
abnormalities noted during the physical examination will be presented in a listing for all subjects. 
8.5 12-lead Electrocardiogram 
Summary tables will be presented for QTcF for subjects in the safety population. Observed 
results at the scheduled visits and changes from baseline to post-baseline visits will be presented. 
All ECG data by subject will be presented in a listing. 
9. Interim Analysis and Supplemental Analysis 
No interim analysis is planned for this study. 
10. Tables, Listings, and Figures 
A list of tables, listings, and figures will be maintained outside of this document and may be 
amended as needed.