Conditions: Coccidioidomycosis
Keywords: Adults Healthy Pharmacokinetics Phase 1 Safety Single Oral Doses Tolerability VT-1598
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 48
Healthy volunteers: yes

Brief summary:
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study in healthy adult subjects ages 18 - 45 years inclusive. It is designed to evaluate the safety and PK of single oral doses of VT-1598. Forty-eight subjects will be enrolled in the study at 1 site in the US and randomized to receive either VT-1598 or placebo in 6 dosage cohorts (five fasted cohorts and one fed cohort). Each cohort will have 8 subjects; 6 subjects will receive a single oral dose of VT-1598 and 2 subjects will receive matching placebo. Cohorts 1 - 5 will include 2 sentinel subjects randomized to different treatments. Cohort 6 (receiving treatment after being fed a high-calorie, high-fat meal) will not include sentinel subjects. Subjects will be admitted to the study site before dosing and remain at the study site for safety monitoring and PK assessments for at least 72 hours post-dose. Subjects will return to the study site on study Days 7, 14, and 21 for outpatient safety monitoring and PK assessments. There are no formal hypotheses being tested in this Phase 1 trial study. The primary objectives of this study are 1) to determine the safety of single-ascending oral doses of VT-1598 in healthy adult subjects in a fasted state, and 2) to determine the safety of single oral dose of VT-1598 in healthy adult subjects in a fed state.

Detailed description:
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study in healthy adult subjects ages 18 - 45 years inclusive. It is designed to evaluate the safety and PK of single oral doses of VT-1598. Forty-eight subjects will be enrolled in the study at 1 site in the US and randomized to receive either VT-1598 or placebo in 6 dosage cohorts (five fasted cohorts and one fed cohort). Cohorts 1 - 4 will run sequentially, but Cohorts 5 and 6 may be started concurrently. Each cohort will have 8 subjects; 6 subjects will receive a single oral dose of VT-1598 and 2 subjects will receive matching placebo. Cohorts 1 - 5 will include 2 sentinel subjects randomized to different treatments. Cohort 6 (receiving treatment after being fed a high-calorie, high-fat meal) will not include sentinel subjects. VT-1598 will be administered in the following escalation schedule: Cohort 1 will receive 40 mg dose, Cohort 2 will receive 80 mg dose, Cohort 3 will receive 160 mg dose, Cohort 4 will receive 320 mg dose, Cohort 5 will receive 640 mg dose, and Cohort 6 (fed cohort) will receive 160 mg dose. Subjects will be admitted to the study site before dosing and remain at the study site for safety monitoring and PK assessments for at least 72 hours post-dose. Subjects will return to the study site on study Days 7, 14, and 21 for outpatient safety monitoring and PK assessments. There are no formal hypotheses being tested in this Phase 1 trial study. The primary objectives of this study are 1) to determine the safety of single-ascending oral doses of VT-1598 in healthy adult subjects in a fasted state, and 2) to determine the safety of single oral dose of VT-1598 in healthy adult subjects in a fed state. The secondary objectives of this study are 1) to determine the pharmacokinetic (PK) profile in plasma and urine of VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects, and 2) to determine the effect of a high-fat, high-calorie meal on the PK profile of VT-1598 and VT-11134 when a single oral dose of VT-1598 is given.

Arms:
arm 1: 40 mg (1 tablet of 40 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner. arm 2: 80 mg (2 tablets of 40 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner. arm 3: 160 mg (4 tablets of 40 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner. arm 4: 320 mg (4 tablets of 80 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner. arm 5: 640 mg (8 tablets of 80 mg) of VT-1598 administered orally as a single dose, n=6 (1 sentinel, 5 non-sentinel), or matching placebo, n=2 (1 sentinel, 1 non-sentinel), while fasting on Day 1 in a double-blind manner. arm 6: 160 mg (4 tablets of 40 mg) of VT-1598 administered orally as a single dose, n=6, or matching placebo, n=2, after high-calorie, high-fat meal on Day 1 in a double-blind manner.

Interventions: intervention 1: Placebo intervention 2: VT-1598
Intervention descriptions: intervention 1: Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing the inactive components of VT-1598. intervention 2: VT-1598 is a novel oral agent for the treatment of fungal infections. It will be supplied as 40 mg and 80 mg tablets.

Protocol document:
Prot_000.pdf: 
DMID Protocol 17-0087 
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CONFIDENTIAL 
  
A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo-
Controlled, Single Dose-Escalation Study to Evaluate the Safety and 
Pharmacokinetics of Single Oral Doses of VT-1598 in Healthy Adult 
Subjects 
 
DMID Protocol Number: 17-0087 
DMID Funding Mechanism: HHSN272201500007I 
Pharmaceutical Support: NQP 1598, Ltd. 
IND Sponsor: DMID 
Lead Principal Investigator:  Cassandra Key, MD 
DMID Clinical Project Manager:  Maureen Mehigan 
Draft or Version Number:  5.0 
Day Month Year 
18 Jun 2021 
 
 
 


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STATEMENT OF ASSURANCE 
Each Institution will hold a current Federal Wide Assurance (FWA) issued by the Office of 
Human Research Protections (OHRP) for federally-funded human subjects research.  Each FWA 
will designate at least one Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) registered with OHRP, for which the research will be reviewed and approved by the 
IRB/IEC and will be subject to continuing review [45 CFR 46.103(b)]. The IRB/IEC designated 
under an FWA may include an institution’s IRB/IEC, an independent IRB/IEC, or an IRB/IEC of 
another institution after establishing a written agreement with that other institution. 
 


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STATEMENT OF COMPLIANCE 
The study trial will be carried out in accordance with Good Clinical Practice (GCP) and as 
required by the following: 
• 
United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of Human 
Subjects; 
• 
Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 
(Protection of Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical 
Investigators), 21 CFR Part 56 (Institutional Review Boards), 21 CFR Part 11, and 21 
CFR Part 312 (Investigational New Drug Application);  
• 
International Conference on Harmonization: Good Clinical Practice (ICH E6); 62 Federal 
Register 25691 (1997); and future revisions; 
• 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects 
of Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research; 
• 
National Institutes of Health (NIH) Office of Extramural Research, Research Involving   
Human Subjects, as applicable;  
• 
National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of Award, 
as applicable; 
• 
Applicable Federal, State, and Local Regulations and Guidance. 
 


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SIGNATURE PAGE 
Protocol Title:  A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo-Controlled, 
Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses 
of VT-1598 in Healthy Adult Subjects 
Protocol Number: 17-0087 
Protocol Version (Issue Date): 
The signature below provides the necessary assurance that this trial will be conducted according 
to all stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal regulations and 
ICH E6 Good Clinical Practice (GCP) guidelines. 
I agree to conduct the study in compliance with GCP and applicable regulatory requirements. 
I agree to conduct the study in accordance with the current protocol and will not make changes to 
the protocol without obtaining the sponsor’s approval and IRB/IEC approval, except when 
necessary to protect the safety, rights, or welfare of subjects. 
Site Investigator Signature: 
 
Signed: 
 
Date: 
 
 
Cassandra Key, MD 
Site Principal Investigator 
 
 
 
 


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TABLE OF CONTENTS 
STATEMENT OF ASSURANCE ...................................................................................................2 
STATEMENT OF COMPLIANCE .................................................................................................3 
SIGNATURE PAGE .......................................................................................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES .........................................................................................................................10 
LIST OF FIGURES .......................................................................................................................11 
LIST OF ABBREVIATIONS ........................................................................................................12 
PROTOCOL SUMMARY .............................................................................................................15 
 
KEY ROLES.........................................................................................................................20 
 
BACKGROUND AND SCIENTIFIC RATIONALE ..........................................................21 
 
Background .................................................................................................................21 
 
Scientific Rationale .....................................................................................................25 
 Purpose of Study ............................................................................................25 
 Study Population ............................................................................................26 
 
Potential Risks and Benefits .......................................................................................27 
 Potential Risks ...............................................................................................27 
 Potential Benefits ...........................................................................................29 
 
STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR OUTCOME MEASURES .....30 
 
Study Design Description ...........................................................................................30 
 Overall Study Design .....................................................................................30 
 Dosing Scheme and Duration of Study ..........................................................30 
 Number of Subjects ........................................................................................31 
 Rationale for Starting Dose ............................................................................31 
 Dose Escalations ............................................................................................31 
 
Study Objectives .........................................................................................................32 
 Primary ...........................................................................................................32 
 Secondary .......................................................................................................32 


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 Study Endpoints or Outcome Measures .........................................................33 
 Primary Outcome Measures ...........................................................................33 
 Secondary Outcome Measures .......................................................................33 
 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT .........................................34 
 
Study Product Description ..........................................................................................34 
 Formulation, Packaging, and Labeling ..........................................................34 
 Product Storage and Stability .........................................................................34 
 
Acquisition/Distribution .............................................................................................34 
 
Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/Investigational Product.........................................................................35 
 
Accountability Procedures for the Study Intervention/Investigational Product(s) .....35 
 
SELECTION OF SUBJECTS AND STUDY ENROLLMENT AND WITHDRAWAL ....37 
 
Eligibility Criteria .......................................................................................................37 
 Subject Inclusion Criteria...............................................................................37 
 Subject Exclusion Criteria .............................................................................38 
 
Withdrawal from the Study, Discontinuation of Study Product, or Study Termination
 ..................................................................................................................................40 
 Withdrawal from the Study or Discontinuation of the Study Product ...........40 
 Subject Replacement ......................................................................................42 
 Study Termination .........................................................................................42 
 
STUDY PROCEDURES ......................................................................................................43 
 
Screening ....................................................................................................................43 
6.1.1 Day -28 to Day -2 (Screening) .......................................................................43 
 
Enrollment ..................................................................................................................44 
6.2.1 Day -1 (Admission to Clinic; approximately 24 hours prior to dosing) ........44 
 
Treatment Period ........................................................................................................45 
6.3.1 Day 1 – Inpatient CRU ..................................................................................45 
 Day 2 – Inpatient CRU ..................................................................................46 
 Day 3 – Inpatient CRU ..................................................................................47 


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 Day 4 – Discharge from CRU ........................................................................47 
 
Follow-up ....................................................................................................................48 
 Day 7 ± 1 ........................................................................................................48 
6.4.2 Day 14± 1 .......................................................................................................49 
6.5 
Final Study Visit .........................................................................................................50 
6.5.1 Day 21 ± 2 ......................................................................................................50 
 
Early Termination Visit ..............................................................................................51 
 
Unscheduled Study Visits ...........................................................................................51 
 
Protocol Deviations ....................................................................................................52 
 
DESCRIPTION OF CLINICAL AND LABORATORY EVALUATIONS .......................53 
 
Clinical Evaluations ....................................................................................................53 
 Safety Tests and Assessments ........................................................................53 
 Assessment of Concomitant Medications/Treatments other than Study 
Product ...........................................................................................................55 
 Assessment of Subject Compliance with Study Intervention/Investigational 
Product/Investigational Device ......................................................................57 
 
Laboratory Evaluations ...............................................................................................57 
 Clinical Laboratory Evaluations ....................................................................57 
 Research Assays .............................................................................................59 
 
ASSESSMENT OF SAFETY ...............................................................................................62 
 
Assessing and Recording Safety Parameters ..............................................................62 
 Adverse Events (AEs) ....................................................................................62 
 
Serious Adverse Events (SAEs) .................................................................................63 
 
Specification of Safety Parameters .............................................................................64 
 Dose Escalation Criteria ................................................................................64 
 Reporting Serious Adverse Events ................................................................65 
 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND
 ........................................................................................................................66 
 Reporting of Pregnancy .................................................................................66 
 
Type and Duration of Follow-up of Subjects after Adverse Events ...........................67 


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Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings......................................................................................67 
 
Halting Rules ..............................................................................................................67 
 Study Halting Criteria ....................................................................................67 
 Dose Escalation Halting Criteria....................................................................68 
 
Safety Oversight .........................................................................................................68 
 Independent Safety Monitor (ISM) ................................................................68 
 Safety Monitoring Committee (SMC) ...........................................................69 
 
HUMAN SUBJECTS PROTECTION .................................................................................71 
 
Institutional Review Board/Independent Ethics Committee ......................................71 
 
Informed Consent Process ..........................................................................................71 
 
Consent for Future Use of Stored Specimens and Data .............................................73 
 
Exclusion of Women, Minorities, and Children (Special Populations) ......................74 
 
Subject Confidentiality ...............................................................................................74 
 
Certificate of Confidentiality ......................................................................................75 
 
Costs, Subject Compensation, and Research Related Injuries ...................................75 
 
STATISTICAL CONSIDERATIONS .................................................................................77 
 Study Hypotheses .......................................................................................................77 
 Sample Size Considerations .......................................................................................77 
 Treatment Assignment Procedures .............................................................................77 
 Randomization Procedures ............................................................................77 
 Masking Procedures .......................................................................................79 
 Planned Interim Analyses ...........................................................................................80 
 Final Analysis Plan .....................................................................................................80 
 Adverse and Serious Adverse Events ............................................................80 
 Clinical Safety Labs, Vital Signs, and Electrocardiograms ...........................80 
 Pharmacokinetic Analysis Plan ..................................................................................81 
 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ..............83 
 Compliance with Standards of Medical Research/ Deviations ...................................83 


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QUALITY CONTROL AND QUALITY ASSURANCE ...................................................84 
 
DATA HANDLING AND RECORD KEEPING ................................................................85 
 Data Management Responsibilities ............................................................................85 
 Data Coordinating Center/Biostatistician Responsibilities ........................................86 
 Data Capture Methods ................................................................................................86 
 Types of Data ..............................................................................................................87 
 Study Records Retention ............................................................................................87 
 
CLINICAL MONITORING .................................................................................................88 
 Site Monitoring Plan ...................................................................................................88 
 
PUBLICATION POLICY ....................................................................................................89 
 
LITERATURE REFERENCES ............................................................................................90 
 
APPENDICES ......................................................................................................................92 
 
VT-1598 SCHEDULE OF STUDY PROCEDURES AND 
EVALUATIONS ......................................................................................................93 
 
VT-1598 TOXICITY GRADING CRITERIA FOR NORMAL 
HUMAN SUBJECTS ...............................................................................................97 
 
 


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LIST OF TABLES 
Table 1: Single Dose* Escalation ..................................................................................................18 
Table 2: Blood PK Sampling Timepoints ......................................................................................59 
Table 3: Urine PK Sampling Timepoints.......................................................................................60 
Table 4: Total Volume of Blood Drawn From Each Subject ........................................................60 
 
 


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LIST OF FIGURES 
Figure 1: 
 Schematic of Study Design ........................................................................................19 
 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
ACTH 
Adrenocorticotropic Hormone 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BMI 
Body Mass Index 
CAR 
Clinical Agents Repository 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CMS 
Clinical Material Services 
CPKt 
Creatinine Phosphokinase 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CROMS 
Clinical Research Operations and Management Support 
CRU 
Clinical Research Unit 
CYP 
Cytochrome P 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDTA 
Ethylenediaminetetraacetic Acid 
FDA 
Food and Drug Administration 


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FSH 
Follicle Stimulating Hormone 
GGT 
Gamma-Glutamyl Transferase  
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HBsAg 
Hepatitis B Surface Antigen 
HCV 
Hepatitis C Virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HLGT 
High-Level Group Term 
ICF 
Informed Consent Form 
ICH 
The International Council for Harmonization  
ICON BAL 
ICON Bioanalytical Laboratory 
ICON GPHS 
ICON Government and Public Health Solutions 
IEC 
Independent or Institutional Ethics Committee 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IUD 
Intrauterine Device 
LARC 
Long Acting Reversible Contraceptive 
LC-MS/MS 
Liquid Chromatography with Tandem Mass Spectrometry 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 


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NEJM 
New England Journal of Medicine 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOAEL 
No-Observed-Adverse-Effect-Level 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
QA 
Quality Assurance 
QC 
Quality Control 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOCS 
Safety Oversight Committee Support 
SOP 
Standard Operating Procedure 
ULN 
Upper Limit of Normal 
US 
United States 
VCT 
Verified Clinical Trials 
WHO 
World Health Organization 
 
 
 


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PROTOCOL SUMMARY 
 
Title: 
A Phase 1, First-In-Human, Randomized, Double-Blind, 
Placebo-Controlled, Single Dose-Escalation Study to Evaluate 
the Safety and Pharmacokinetics of Single Oral Doses of VT-
1598 in Healthy Adult Subjects 
Design of the Study: 
 
This is a Phase 1, first-in-human, randomized, double-blind, 
placebo-controlled, single ascending dose (SAD) study, in six (6) 
cohorts (five fasted cohorts, one fed cohort).  Each cohort 
contains 8 subjects (N = 8), 6 subjects will be given an oral dose 
of VT-1598 and 2 subjects will receive placebo. 
Study Phase: 
1 
Study Population: 
Up to forty-eight (48) healthy male and female subjects, 
ages 18-45 (inclusive). 
Number of Sites: 
1 
Description of Study 
Product or Intervention: 
VT-1598 will be supplied as 40 mg and 80 mg tablets.  
Placebo will be supplied as the same size, weight, and color as 
the VT-1598 tablets. 
Study Objectives: 
 
 
Primary: 
• To determine the safety of single-ascending oral doses of 
VT-1598 in healthy adult subjects in a fasted state.   
• To determine the safety of single oral dose of VT-1598 in 
healthy adult subjects in a fed state.     
 


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Secondary: 
• To determine the pharmacokinetic (PK) profile in plasma 
and urine of VT-1598 and its primary metabolite, VT-
11134, in healthy adult subjects 
• 
To determine the effect of a high-fat, high-calorie meal on 
the PK profile of VT-1598 and VT-11134 when a single 
oral dose of VT-1598 is given. 
 
Study Outcome Measures: 
Primary: 
• Safety will be evaluated for single-ascending fasting oral 
doses of VT-1598. Safety will be assessed by adverse 
events from start of dosing to Day 21, clinical laboratory 
tests at baseline and from Day 4 to Day 21, ECGs at 
baseline and on Day 4 and Day 21, and vital signs at 
baseline and from Day 1 to Day 21;  
• Safety will be evaluated for single oral dose of VT-1598 
administered after being fed a high-fat, high calorie meal. 
Safety will be assessed by adverse effects from start of 
dosing to Day 21, clinical laboratory tests at baseline and 
from Day 4 to Day 21, ECGs at baseline and on Day 4 and 
Day 21, and vital signs at baseline and from Day 1 to Day 
21.  
Secondary: 
• PK profiles of VT-1598 and its primary metabolite, VT-
11134, will be assessed by measurement of VT-1598 and 
VT-11134 levels in both plasma and urine after VT-1598 
administration in each cohort, when fasting.  Plasma for PK 
analysis will be collected at planned time points up to 480 
hours post-dose and urine for PK analysis will be collected 
in planned intervals up to 72 hours post-dose;  


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• PK profiles of VT-1598 and its primary metabolite, VT-
11134, will be assessed by measurement of VT-1598 and 
VT-11134 levels in both plasma and urine after 
administration of VT-1598 following consumption of a 
high-fat, high calorie meal. Plasma for PK analysis will be 
collected at planned time points up to 480 hours post-dose 
and urine for PK analysis will be collected in planned 
intervals up to 72 hours post-dose.   
Duration of Individual 
Subject Participation: 
Individual subject participation will be approximately 50 days to 
include up to 28 days pre-enrollment (screening period) and 21 
days of follow-up post-dosing. Note: Subjects who participate in 
both cohorts 3 and 6, their participation will exceed 50 days.     
Estimated Time to Last 
Subject/Last Study Day: 
Approximately 6 months. 
 
 
 


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Table 1: Single Dose* Escalation 
Cohort 1 - 
fasting 
Dose:  40 mg 
6 
subjects** 
Single 40 mg VT-1598 
tablet 
Safety data for Cohort 1 subjects through Day 7 will 
be confirmed by reviewing objective pre-defined 
criteria before continuing to Cohort 2. 
 
2 
subjects** 
Single 40 mg 
matching Placebo 
Cohort 2 - 
fasting 
Dose:  80 mg 
6 
subjects** 
Two 40 mg VT-1598 
tablets 
Safety data for Cohort 2 subjects through Day 7 will 
be confirmed by reviewing objective pre-defined 
criteria before continuing to Cohort 3. 
2 
subjects** 
Two 40 mg matching 
Placebo tablets 
Cohort 3 - 
fasting 
Dose:  160 mg 
6 
subjects** 
Four 40 mg VT-1598 
tablets 
Safety data for Cohort 3 subjects through Day 7 will 
be confirmed by reviewing objective pre-defined 
criteria before continuing to Cohort 4 and 6. Interim 
analysis of PK data (Cohorts 1-3)***  
2 
subjects** 
Four 40 mg matching 
Placebo tablets 
Cohort 4 – 
fasting  
Dose:  320 mg 
6 
subjects** 
Four 80 mg VT-1598 
tablets 
Cumulative safety data for all subjects in Cohorts 1-4 
through Day 21 will be reviewed by the SMC for 
recommendation/confirmation of dosing before 
continuing to Cohort 5 
2 
subjects** 
Four 80 mg matching 
Placebo tablets 
Cohort 5 – 
fasting 
Dose: 640 mg 
6 
subjects** 
Eight 80 mg VT-1598 
tablets 
 
 
2 
subjects** 
Eight 80 mg matching 
Placebo tablets 
Cohort 6 – fed 
(high-fat, high-
calorie meal) 
Dose:  160 mg 
6 subjects 
Four 40 mg VT-1598 
tablets 
Cohort 6 is comprised of the same subjects as Cohort 
3****. These subjects will receive the same treatment 
in Cohort 6 as Cohort 3. Cohort 6 may start enrolling 
prior to convening the SMC meeting and prior to the 
start of Cohort 5.  
2 subjects 
Four 40 mg matching 
Placebo tablets 
*Dose refers to the free base equivalent of the drug. 
**Within each fasted cohort two sentinel subjects will be admitted initially, and the randomization scheme will be 
designed to ensure that one subject will receive VT-1598 and the other will receive placebo.  All sentinel subject 
safety data through Day 3 is reviewed by PI prior to dosing remainder of cohort. 
***PK data only; enrollment for Cohort 4 will not stop for the PK interim analysis. 
**** The Cohort 6 replacement subjects will receive the same treatment as assigned to the Cohort 3 subject they are 
replacing. 
 
 


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PK blood sampling (all subjects)
pre-dose; post-dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 14hr
PK urine sampling (all subjects):
pre-dose; post-dose 0-6, 6-12, 12-24 hr
Day 21 (+/- 2 days)
PE, vitals, ECG, clin labs
480hr PK blood samples
Days 7 & 14 outpatient (+/- 1 day)
vitals, clin labs
144 & 312 hour PK blood samples
Day 4
Physical exam, vitals, ECG, Clin labs
72 hr PK blood & 60-72 hr PK urine samples
Discharge from CRU
Days 2 & 3 (confined)
Vitals, Conmeds
 24, 36, 48, 60 hr PK blood samples & 24-36, 36-48, 48-60 hr PK urine samples
Day 1
Study product administration (per cohort dose regimen)
PK blood sampling through 14hr post-dose- PK urine sampling up to 24 hr post-dose (time points below)
Day -1
Enrollment and baseline assessments
Admitted and confined to CRU
Randomization
Up to Day -28
Screening
 
Figure 1: 
 Schematic of Study Design 
 
 


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KEY ROLES 
 
Lead Principal 
Investigator: 
 
                                      
 
 
: 
Cassandra Key, MD 
ICON Early Phase Services, LLC 
8307 Gault Lane 
San Antonio, TX    78209 
Phone: 210-283-4120 
Email: Cassandra.key@iconplc.com  
 
 
DMID Clinical Project 
Manager 
Maureen Mehigan 
5601 Fisher Lane 7E54 
Bethesda, MD  20892 
Phone: 240-627-3317 
Cell: 240-507-9599 
Email: mmehigan@niaid.nih.gov 
Statistical and Data 
Coordinating Center: 
 
Emmes Company, LLC 
401 North Washington Street, Suite 700 
 
Rockville, MD  20850 
Phone: 301-251-1161 
Email: phase1@emmes.com 
Contact information for additional key personnel is located in the Manual of Procedures 
(MOP) for this study. 


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BACKGROUND AND SCIENTIFIC RATIONALE 
 
Background  
CYP51 (lanosterol demethylase) is a metalloenzyme essential for fungal growth and catalyzes an 
early step in the biosynthetic pathway of ergosterol, a sterol required for fungal cell membrane 
formation and integrity.1 Inhibition of CYP51 not only blocks the pathway leading to ergosterol 
but also results in the accumulation of 14-methylated sterols, some of which are toxic to the 
fungus. Fungal CYP51 is the molecular target of the class of drugs referred to as ‘azole 
antifungals’. All currently approved azole drugs contain either an imidazole or triazole ring 
system2 that binds tightly to the catalytic heme-iron of fungal CYP51 as well as to the heme-iron 
of many off-target mammalian cytochrome P450 (CYP) enzymes. This inherent lack of 
selectivity is responsible for many of the side effects associated with the azole antifungals. For 
example, the potent inhibition of one or more human CYP enzymes found in the liver (e.g., 
CYP3A4, CYP2C9, CYP2C19) or in the adrenal and sex organs (e.g., CYP11B, CYP19, 
CYP17) is the basis for azole drug-drug interactions (DDI)3 and endocrine toxicities, including 
reproductive warnings,4 respectively. 
Additional azole class toxicities that are less well understood but may be related to other off-
target human CYP interactions include hepatic toxicity, skin photosensitivity, and vision 
impairment. In the acute care setting, the dose-limiting side effects not only are limitations in and 
of themselves but also prevent attainment of plasma drug levels that might reduce the long-
standing high mortality rates attributed to invasive fungal infections. For example, the mortality 
rate (40%) due to coccidioidal meningitis in a 2008 study has not changed since 1980.5 
VT-1598 is a novel, potent antifungal compound designed to selectively bind to fungal CYP51 
rather than human CYP enzymes so as to minimize the off-target effects associated with 
currently approved azole antifungals agents. In both in vitro and in vivo studies, VT-1598 has 
demonstrated highly-potent antifungal activity against Coccidioides species. 
Approximately 50,000 cases of coccidioidomycosis are estimated to occur annually that are 
sufficiently severe to require medical attention. Among these cases, several thousand patients 
suffer serious pulmonary sequelae, and disseminated infection will result in death in 
approximately 160 individuals.6,7,8,9 The disease can be highly-debilitating and places 
considerable demands on healthcare resources. In a survey of nearly 500 recently diagnosed 
cases of coccidioidomycosis in Arizona, 85% of cases had disease limited to the lungs, the 
median duration of illness was 4 months, and the median time lost from work was 2 weeks. 
Forty-one percent of patients required hospitalization, incurring an average cost of $30,000 per 
patient just for inpatient care.10 From 2000-2011, 25,217 coccidioidomycosis-associated 


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hospitalizations occurred in California, involving 15,747 patients. Among these patients, there 
were 1,220 deaths: 626 due to primary pulmonary coccidioidomycosis, 309 due to other forms of 
progressive disease, and 196 due to coccidioidal meningitis.11 Coccidioidal meningitis is the 
most severe form of disseminated disease, and is associated with a high degree of morbidity and 
mortality. Khan and Brady identified 1251 hospitalizations in 623 patients with coccidioidal 
meningitis in non-federal facilities in Arizona from 2008-2014.12 Readmission was common 
(41%) and 61% of hospitalizations included time in the intensive care unit. 
Treatment regimens (choice of agent and doses) for coccidioidomycosis vary considerably 
depending on the clinical presentation of the disease, and all current regimens have significant 
limitations. Currently, ketoconazole and amphotericin B are the only antifungal agents approved 
for this disease, despite significant toxicity concerns. The Infectious Diseases Society of America 
guidelines recommend that coccidioidomycosis be managed with various antifungal agents 
including off-label use of fluconazole and itraconazole, as well as amphotericin B, depending on 
disease presentation.13 However, with currently available antifungal agents, coccidioidomycosis 
continues to be associated with substantial, preventable morbidity and mortality, and relapse is a 
common occurrence. Treatment outcomes are particularly poor for disseminated disease (~40% 
mortality) and a comparison of matched cohorts from 1980 and 2008 suggests that outcomes did 
not improve over that time span.5 In addition, existing oral agents are generally administered at 
high doses for extended durations and are associated with significant toxicity, including a risk of 
serious hepatotoxicity that increases with dose and duration of treatment. High-dose and 
prolonged use of the commonly-prescribed fluconazole is also associated with congenital 
anomalies in infants exposed in utero. Finally, all prescribed azole antifungals have significant 
DDIs due to poor selectivity for fungal versus human CYP enzymes, complicating both 
treatment decisions and drug monitoring. Therefore, there is an urgent need for new therapeutic 
options that can address gaps in efficacy and provide a better safety profile.  
Nonclinical Studies 
Nonclinical Pharmacology 
Binding and Inhibition 
In vitro pharmacology studies have demonstrated that VT-1598 is a potent inhibitor of fungal 
CYP51 and that the activity of VT-1598 is highly selective for fungal CYP51 versus human 
CYPs. 
 
 


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Microbiology 
VT-1598 was tested under Clinical Laboratory Standards Institute guidelines against a broad 
panel of fungal samples (N = 10-50/species) including clinical yeast, mold and endemic fungal 
isolates, and showed potent intrinsic antifungal activity (geometric mean minimum inhibitory 
concentrations ranging from 0.004 to 3.5 µg/mL for the 15-different species tested). 
Activity in Animal Models of Infection 
In murine models of invasive infections with Coccidioides posadasii, Cryptococcus neoformans, 
Candida albicans, and Aspergillus fumigatus, and of a mucosal infection with C. albicans, VT-
1598 free base or tosylate salt at oral once daily doses ranging from 3 to 50 mg/kg (doses 
expressed as the free base equivalent) were highly effective in reducing fungal burden and 
demonstrated a survival benefit of up to 100% protection across multiple studies. In two models, 
VT-1598 reduced fungal burden to below pre-treatment levels. In murine central nervous system 
models of coccidioidomycosis and cryptococcosis, VT-1598 not only achieved highly significant 
survival benefit, it also reduced brain fungal burden up to 5-6.5 orders of magnitude, with 
undetectable viable fungus in several of the tissue samples assessed. 
Nonclinical Drug Metabolism and Pharmacokinetics 
Pharmacokinetics 
Single-dose PK studies were conducted in Swiss albino mice, Sprague-Dawley rats, Beagle dogs, 
and cynomolgus monkeys, with the primary goal to identify the version/form and formulation 
that would give optimized exposures for preclinical safety assessment. Repeat-dose PK and 
toxicokinetics studies showed that orally administered VT-1598 was well absorbed and reached a 
maximum measured plasma concentration (Cmax) of 30-40 µg/mL in rats and 50-60 µg/mL in 
monkeys after repeated doses up to 28 days in duration. VT-1598 exposures increased as doses 
increased in all animal species, but exposure increases were less than dose-proportional. 
Terminal elimination half-lives were relatively long (25-33 hours in rats and 64-72 hours in 
monkeys), leading to accumulation in repeat-dose studies (2- to 4-fold increases in rats and 10- 
to 15-fold increases in monkeys). In the large majority of studies, no differences were observed 
between males and females (although there were higher exposures in females at the end of the 
28-day Good Laboratory Practice [GLP] rat toxicity study). VT-1598 has very high plasma 
protein binding (≥99.9%). 
Metabolism 
VT-1598 was metabolized to varying extents when incubated with mouse, rat, dog, monkey, or 
human liver microsomes and with rat, dog, and human hepatocytes. A single metabolite was 


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observed following incubations with human hepatocytes; its structure is consistent with O-
dealkylation at the internal ether linkage of VT-1598. 
CYP Interactions 
When tested in biochemical assays using 1 mg/mL microsomal protein, VT-1598 weakly 
inhibited human CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, 
CYP2D6, CYP2E1, CYP3A4, CYP11B1/2, CYP17, and CYP19). The range of half maximal 
inhibitory concentration (IC50) values was 6.8 to >200 µM. When tested in assays using 0.01-0.1 
µg/mL, IC50 values were lower: CYP1A2 (IC50 = >4.5 µM), CYP2D6 (IC50 = >4.5 µM), 
CYP2C9 (IC50 =>4.5 µM), CYP2B6 (IC50 = 3.8 µM), CYP3A4/5 (IC50 = 2.8 µM with 
testosterone as substrate), CYP2C8 (IC50 = 0.96 µM), CYP2C19 (IC50 = 0.91 µM), and 
CYP3A4/5 (IC50 = 0.59 µM) with midazolam as substrate. 
Nonclinical Safety Assessments 
Safety Pharmacology 
The effects of orally-administered VT-1598 on the neurological and pulmonary systems were 
evaluated in Sprague-Dawley rats. No observable adverse effects were found at the top dose of 
150 mg/kg VT-1598 in either study. Evaluation of cardiovascular function in telemetered 
monkeys revealed no adverse changes in heart rate, blood pressure, cardiac rhythm or 
morphology, including the QT/QTc interval, at oral doses up to 300 mg/kg administered twice-
daily for 7 days. VT-1598 did not inhibit the human ether-à-go-go related gene (commonly 
known as hERG) potassium current up to the highest soluble concentration tested (with the 
estimated IC50 of >2.9 µM). 
Toxicology 
Oral VT-1598 has been evaluated in general toxicity studies in rats and monkeys of up to 28 
days in duration. Based on the pivotal 28-day GLP toxicology studies, rats were more sensitive 
to the toxicological effects of oral administration of VT-1598 than monkeys. 
In the 28-day GLP rat toxicity study, once daily oral doses of VT-1598 resulted in test article- 
related mortality at 300 mg/kg/day. VT-1598-related changes in body weight, food consumption, 
clinical pathology parameters, organ weights and/or histopathology were observed ≥10 
mg/kg/day but were considered to be non-adverse. Exposure to VT-1598 and its primary 
metabolite (VT-11134) increased less than proportionally to the increase in dose and 
accumulated with repeated dosing as predicted by the long half-life of the molecule (terminal 
elimination half-life was calculated to be 25-33 hours). The no-observed-adverse-effect-level 
(NOAEL) for VT-1598 established in this study was 100 mg/kg/day; Day 28 Cmax and an area 
under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-


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24) in males were 12.6 μg/mL and 201 µghr/mL, respectively, and Cmax and AUC24 values in 
females were 32.0 μg/mL and 475 µg·hr/mL, respectively. 
In the 28-day GLP oral toxicity study in cynomolgus monkeys following twice daily dosing with 
VT-1598, findings were generally limited to the highest dose tested (100 mg/kg/dose) and 
included clinical observations, mild increase in QTc interval, and increased organ weights with 
correlative histopathological changes. Increased adrenal gland and liver weights were associated 
with cortical hypertrophy and hepatocellular hypertrophy, respectively, which were observed 
across dose-groups, although not necessarily dose-dependent. No test article-related changes 
were present in recovery animals. Exposure to VT-1598 and VT-11134 generally increased in a 
dose- related manner; however, the increase in exposure was less than proportional to the 
increase in dose. VT-1598 and VT-11134 accumulated with repeated dosing as predicted by the 
long half- life of the molecule (terminal elimination half-life was calculated to be 64-72 hours). 
The NOAEL for VT-1598 for this study was the high dose level of 100 mg/kg/dose (200 
mg/kg/day), associated with a Day 28 Cmax of 65.2 µg/mL, and AUC24 of 1,330 µgh·r/mL. 
Genotoxicity 
VT-1598 was found to be negative for genotoxicity in the in vitro bacterial reverse mutation 
assay, the in vitro chromosome aberrations assay in human peripheral lymphocytes, and the in 
vivo bone marrow micronucleus assay in rats. 
Clinical Studies 
To date, no clinical studies have been conducted with VT-1598.  
 
Scientific Rationale 
 
Purpose of Study 
Coccidioidomycosis, also called Valley Fever, is an infectious disease caused by dimorphic fungi 
of the genus Coccidioides. Coccidioides species (C. immitis and C. posadasii) are endemic to the 
lower Sonoran life zone of the western hemisphere, including southern Arizona, the southern and 
central valleys of California, southwestern New Mexico, and west Texas in the US.6 Recent 
reports have documented the presence of C. immitis as far north as south-central Washington 
state.14 
In endemic states in which coccidioidomycosis is reportable to the US Centers for Disease 
Control and Prevention (CDC); (Arizona, California, Nevada, New Mexico, and Utah), the 
incidence of coccidioidomycosis increased from 5.3 cases per 100,000 population in 1998 to 
42.6 cases per 100,000 population in 2011.15 During that time period, 111,717 cases of 
coccidioidomycosis were reported to the CDC.15 Arizona and California account for 66 and 31 


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percent, respectively, of all nationally reported infections.15 Reportable-disease data rely on 
positive diagnostic test results and given the low rate of testing even in highly endemic areas, it 
is clear that the actual number of coccidioidomycosis cases far exceeds the reported numbers.16 
With population and industrial expansion into the southwestern deserts, the numbers of 
infections are expected to continue to climb. Additionally, the National Institute of Allergy and 
Infectious Diseases (NIAID) has designated Coccidioides species as a Category C pathogen due 
to its potential to be engineered as a bioterrorism weapon.17 
VT-1598 has been shown in preclinical studies to be a potent and selective, orally-available 
inhibitor of fungal CYP51. Fungal CYP51 is the target of the azole class of antifungal drugs. 
Azoles rely heavily on the potent interaction between either an imidazole or triazole moiety and 
the active site heme iron of this CYP, which also leads to potent inhibition of human CYPs. VT-
1598 blocks the production of ergosterol, an essential component of the fungal cell membrane. 
Due to VT-1598’s high fungal CYP selectivity, low cross reactivity with human CYP, and 
highly-potent antifungal activity, VT-1598 should have a greater clinical safety margin than 
currently available azole antifungal treatments. As a result of VT-1598’s substantial potency 
against Coccidioides species, VT-1598 was selected for further preclinical development targeting 
the treatment of coccidioidomycosis. 
 
Study Population 
Up to 48 subjects aged 18-45 (inclusive) who are in good health and meet all eligibility criteria 
will be enrolled in the study. The demographics in the local population should ensure that male, 
female and minorities (African American and Hispanics) will be represented in the enrolled 
population. Subjects will be recruited using IRB-approved advertising/web site listing of the 
essential inclusion and exclusion criteria. Subjects will self-schedule online for a screening 
appointment based on their desire to participate and their evaluation of their suitability based on 
inclusion/exclusion criteria. Children, pregnant or breast-feeding women, prisoners, and other 
vulnerable populations will not be enrolled. See Section 9.4 Exclusion of Women, Minorities and 
Children (Special Populations). 
Neither women nor minorities will be excluded from participation in this study. Women of child 
bearing potential may be included as per the inclusion criteria (Section 5.1 Eligibility Criteria). 
Subjects will be recruited without regard to gender or race. It is expected that race will reflect 
that within the community.  


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Potential Risks and Benefits 
 
Potential Risks 
As VT-1598 has not yet been studied in humans, no information is currently available regarding 
AEs associated with its use. 
When oral VT-1598 was evaluated in general toxicity studies in rats and monkeys, the following 
side effects were noted:   
- slight decreases in body temperature and heart rate 
- minimal to mild increases in serum cholesterol 
- decreases in mean body weight and food consumption 
- decreases in lymphocyte and eosinophil counts and/or increases in monocyte counts 
- moderate to marked prolongations of APTT and prothrombin times 
- minimal to mild decreases in alkaline phosphatase 
- mild to moderate decreases in serum albumin 
- mild decrease in serum creatinine 
- mild to moderate, dose-dependent increases in gamma-glutamyl transferase (GGT) 
- mild to moderate decreases in urine pH and specific gravity 
- mild increase in urine volume. 
 
Among the currently-available azole antifungal agents, numerous clinically-significant drug 
interactions have been identified.18  Most of these interactions are a result of competitive 
inhibition of liver oxidative metabolism via reversible binding to CYP enzymes. Azoles interfere 
mainly with CYP3A4, CYP2C9, and CYP2C19 characterized by individual affinity and they 
therefore exhibit slightly different drug interaction profiles. In addition, itraconazole, 
posaconazole and isavuconazole are inhibitors of gastric P-glycoprotein, which limits systemic 
exposure to many drugs by inhibiting gastrointestinal absorption. 
Adverse effects of the currently-available azole antifungals vary across the individual agents and 
are described in the following paragraphs: 
Fluconazole: Fluconazole is generally well tolerated and serious adverse events (SAEs), mainly 
hepatotoxicity, are rare. Gastrointestinal disturbances are the most common complaints. High 
doses (400-800 mg/day) of fluconazole may be associated with a rare and distinct set of birth 
defects in infants whose mothers were treated with the drug during the first trimester of 
pregnancy. The US Food and Drug Administration (FDA) is evaluating the results of a Danish 
study that concluded there is a possible increased risk of miscarriage with the use of oral 
fluconazole for yeast infections. 


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Ketoconazole: Nausea and vomiting may occur when using ketoconazole. Serious and 
sometimes fatal liver problems, including the need for liver transplant, have occurred with the 
use of ketoconazole. Ketoconazole can cause elevated plasma concentrations of certain drugs 
and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias 
such as torsades de pointes. Ketoconazole, when used in high doses, may cause adrenal 
insufficiency. 
Itraconazole: Itraconazole causes frequent gastrointestinal symptoms, mainly nausea and 
vomiting; other common adverse effects include elevated hepatic transaminases, hypokalemia 
(sometimes severe), and rashes. Serious hepatotoxicity leading to liver failure has been reported 
with itraconazole but is rare. Heart failure due to itraconazole is caused by a direct negative 
inotropic effect and has resulted in a “black box” warning in the label. 
Voriconazole: The most common AEs after treatment with voriconazole include visual 
disturbances in up to 20-40% of recipients. Most reports are of blurring, photopsia, photophobia, 
and color changes soon after dosing; these are reversible and tend to dissipate with continued 
dosing. Like the other triazoles, voriconazole has been associated with hepatotoxicity which can 
rarely be serious or fatal and is dose-related. Other side effects include visual and auditory 
hallucinations, confusion, skin rashes (mostly photosensitivity), QTc prolongation, and 
peripheral neuropathy. 
Posaconazole: The safety profile of posaconazole is improved compared to voriconazole. 
Common AEs include headaches and gastrointestinal disturbances. Hepatotoxicity is uncommon 
and reported in 2-3% of recipients. Hypokalemia and rashes occur but less commonly than with 
itraconazole and voriconazole. 
Isavuconazole: The most frequent adverse effects of isavuconazole are nausea, vomiting, 
diarrhea, headache, elevated liver chemistry tests, hypokalemia, constipation, dyspnea, cough, 
peripheral edema and back pain. Isavuconazole is contraindicated for use in patients with 
familial short QT syndrome and rare but serious hepatic reactions have also been reported with 
its use. 
As noted above, the differentiating properties of VT-1598 should translate to greater efficacy 
with an improved safety and tolerability profile compared to the existing azole agents. In 
addition, the animal toxicology studies completed to date do not suggest any unusual or 
unexpected toxicities related to VT-1598 exposure. The present study provides for careful 
monitoring for the AEs that have been observed with existing azole agents. In addition, all 
subjects that have pre-existing abnormalities in body systems associated with the more severe 
AEs reported for existing azoles (e.g., visual disturbances, hepatic disease, and cardiac 
conduction abnormalities) will be excluded from participation. 


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As with taking any product/drug, there is a risk of allergic reaction. There may be risk of death if 
there is a very serious allergic reaction. Other risks include temporary physical discomfort and 
potential emotional stress due to the nature of the exams and specimen collection procedures. 
The risks associated with insertion of the indwelling intravenous catheter and frequent blood 
draws are fainting, pain, bruising, and scarring. The catheter may be at risk for clotting and 
infection.  These risks are discussed with the subject during the consent process. 
  
In addition to the above risks, the risk of volunteering for this study includes a potential failure to 
protect the subject’s private health and other information through an accidental breach of 
confidentiality.  This risk of breach of confidentiality and the associated safeguards to protect 
confidentiality will be defined in each informed consent document. 
 
 
Potential Benefits 
There are no known benefits to subjects participating in this study. The knowledge gained in this 
trial may help society, especially those exposed to Coccidioides species. 


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STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR 
OUTCOME MEASURES 
 
Study Design Description 
 Overall Study Design 
This is a Phase 1, randomized, double-blind, placebo-controlled, SAD study in healthy adult 
subjects. It is designed to evaluate the safety and PK of single oral doses of VT-1598. Subjects 
who provide informed consent and meet all study eligibility criteria will be enrolled in the study 
and randomized to receive either VT-1598 or placebo in 6 dosage cohorts (five fasted cohorts 
and one fed cohort).  For all cohorts, Screening, Enrollment, Treatment Period, and Follow-Up 
procedures/activities (Day -28 to Day 21) will follow the same process, with the exception of the 
fed Cohort (Cohort 6) who receives the study product after a high-calorie, high-fat meal vs. when 
fasted (Cohorts 1-5).  Cohort 6 may be started prior to the SMC meeting or prior to the start of 
Cohort 5 (but no less than 60 days following their first dose after completion of Cohort 3). 
  Dosing Scheme and Duration of Study 
For each dosage cohort, 6 subjects will receive VT-1598 and 2 subjects will receive placebo. 
Within each of the fasted cohorts (Cohorts 1-5), two sentinel subjects will be admitted initially, 
and the randomization scheme will be designed to ensure that one subject will receive VT-1598 
and the other will receive placebo.  The dosing of the next 6 subjects for each subsequent fasting 
dose escalation group (Cohorts 2-5) will not be initiated until at least 3 days have passed and 
none of the predefined objective halting criteria for sentinels have been met. The remaining 6 
subjects in the cohort will then be admitted and dosed.  
Pending subject availability, the fed group (Cohort 6) will be comprised of the same subjects as 
Cohort 3, however they will not be randomized; the same 6 subjects who received VT-1598 and 
the 2 subjects who received placebo in Cohort 3 will receive the same treatment in Cohort 6. 
Cohort 6 subjects are dosed at the same level as Cohort 3 (160 mg) following a high-fat, high-
calorie meal.  Cohort 6 will not include sentinel subjects. Providing no halting criteria is met, 
Cohort 3 subjects may proceed to Cohort 6 and be dosed prior to the Safety Monitoring 
Committee meeting but no less than 60 days following their first dose (wash-out period). 
Subjects who complete Cohort 3 but are not eligible or withdraw prior to dosing for Cohort 6 
will be replaced.  The Cohort 6 replacement subjects will receive the same treatment as assigned 
to the Cohort 3 subject they are replacing.  


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Safety data through Day 7 for every subject in the current cohort will be available prior to 
making dose escalation decisions. Dose escalation may occur if none of the predefined objective 
halting criteria for dose escalation have been met. The duration of individual subject 
participation, from start of screening until final follow-up, will be up to 50 days (Note: Subjects 
who participate in cohort 3/6, their participation will exceed 50 days). Screening for eligibility 
will occur from Day -28 to Day -2. Subjects will be admitted to the CRU on the day before 
dosing (Day -1). Subjects will be administered VT-1598 or placebo on Day 1 and will remain in 
the CRU for at least 72 hours post-dose (Day 4) for safety monitoring and PK assessments. 
Subjects will return to the CRU on Days 7, 14, and 21 for safety monitoring and PK assessments. 
The study duration from the start of screening until last follow-up of the last dose cohort will be 
approximately 6 months. 
 Number of Subjects 
A sufficient number of subjects will be screened to enroll up to 48 subjects into the study in 6 
cohorts, and each cohort contains 8 subjects (6 for active drug VT-1598 and 2 for placebo). 
Cohort 6 (fed Cohort).Subjects will be enrolled from 1 site in the US. 
 Rationale for Starting Dose 
The proposed clinical start dose is based on the FDA guidance document “Estimating the 
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Healthy Volunteers”, 
July 2005. The rat was determined to be the most sensitive species in 28-day toxicity studies. 
The NOAEL for this study was 100 mg/kg/day (dose expressed as the free base equivalent 
throughout the document). Using 100 mg/kg/day as the NOAEL in rat, the human equivalent 
dose calculation of 40 mg for a starting dose incorporates a 28-fold safety margin.   
 Dose Escalations 
The initial cohort of 8 subjects will be administered 40 mg of VT-1598 (6 subjects) or placebo (2 
subjects) as a single oral dose. Two sentinel subjects will be included in cohorts 1-5 as described 
in Section 3.1.2 Dosing Scheme and Duration of Study.  
Dose escalation to each successive cohort will occur if none of the predefined dose escalation 
halting criterion is met (for all subjects through Day 7). This will be communicated through the 
following process: 
1. A halting criteria report will be provided by the SDCC to the study  
2. If based on the data entered in EDC, none of the halting criteria are met, then the email 
from the SDCC will be provided and the Sponsor will notify the study team that the next 
cohort can be opened for enrollment.    


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3. If any of the halting criteria are met, the SDCC will provide the dose escalation report 
and an ad-hoc SMC meeting will be convened to seek recommendation from the SMC. 
 
There will be a scheduled SMC data review meeting prior to start of Cohort 5.  
The nominal dose-escalation scheme will be 40, 80, 160, 320 and 640 mg or matching placebo 
administered in a fasting state. The effect of a high-fat, high-calorie meal on the PK of VT-1598 
is planned in an additional cohort that will be dosed at 160 mg.  The fed cohort will be dosed at 
160 mg, after the 320 mg fasted cohort has been dosed. This provides additional safety data to 
cover the possibility that the bioavailability of VT-1598 is increased in the presence of food. The 
highest proposed dose in this study is 640 mg, which is 53% of the body surface area equivalent 
of the NOAEL in the most sensitive species.   
In order to efficiently identify the optimal therapeutic doses for use in future clinical trials, a 
flexible scheme of dose escalation, (based on ongoing study data) will be used that allows 
intermediate doses higher or lower than the planned doses (40, 80, 160, 320 and 640 mg), upon 
protocol amendment and with IRB approval.   However, no cohort will be dosed higher than the 
640 mg free base equivalent. 
See Figure 1 Schematic of Study Design. 
 
Study Objectives 
 Primary  
• 
To determine the safety of single-ascending oral doses of VT-1598 in healthy adult subjects 
in a fasted state;   
• 
To determine the safety of single oral dose of VT-1598 in healthy adult subjects in a fed 
state.     
 Secondary 
• 
To determine the pharmacokinetic (PK) profile in plasma and urine of VT-1598 and its 
primary metabolite, VT-11134, in healthy adult subjects; 
• 
To determine the effect of a high-fat, high-calorie meal on the PK profile of VT-1598 and 
VT-11134 when a single oral dose of VT-1598 is given. 


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 Study Endpoints or Outcome Measures 
 Primary Outcome Measures 
• 
Safety will be evaluated for single-ascending fasting oral doses of VT-1598. Safety will be 
assessed by adverse events from start of dosing to Day 21, clinical laboratory tests at 
baseline and from Day 4 to Day 21, ECGs at baseline and on Day 4 and Day 21, and vital 
signs at baseline and from Day 1 to Day 21;  
• 
Safety will be evaluated for single oral dose of VT-1598 administered after being fed a 
high-fat, high calorie meal. Safety will be assessed by adverse effects from start of dosing to 
Day 21, clinical laboratory tests at baseline and from Day 4 to Day 21, ECGs at baseline and 
vital signs at baseline and from Day 1 to Day 21.  
 Secondary Outcome Measures 
• 
PK profiles of VT-1598 and its primary metabolite, VT-11134, will be assessed by 
measurement of VT-1598 and VT-11134 levels in both plasma and urine after VT-1598 
administration in each cohort, when fasting.  Plasma for PK analysis will be collected at 
planned time points up to 480 hours post-dose and urine for PK analysis will be collected in 
planned intervals up to 72 hours post-dose;  
• 
PK profiles of VT-1598 and its primary metabolite, VT-11134, will be assessed by 
measurement of VT-1598 and VT-11134 levels in both plasma and urine after 
administration of VT-1598 following consumption of a high-fat, high calorie meal. Plasma 
for PK analysis will be collected at planned time points up to 480 hours post-dose and urine 
for PK analysis will be collected in planned intervals up to 72 hours post-dose.   
 
 
 


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STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
 
Study Product Description 
VT-1598 is a novel oral agent for the treatment of fungal infections. VT-1598 in its physical 
form is a lightly colored solid with a molecular formula of C31H20F4N6O2 and a molecular weight 
of 584.5 g/mol. 
 Formulation, Packaging, and Labeling 
VT-1598 will be supplied as 40 mg and 80 mg tablets. Each tablet is formulated as a spray-dried 
dispersion with standard excipients including Eudragit® L100, microcrystalline cellulose, 
mannitol, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, and FD&C 
Yellow #5 aluminum lake (United States Pharmacopeia).  
Placebo will be supplied as matching tablets (to 40 mg and 80 mg VT-1598 tablets) containing 
the inactive components of VT-1598.  In order to maintain the blind, the placebo tablets, are the 
same size, weight, and color as the VT-1598 tablets.  
VT-1598 and placebo tablets will be packaged in identical white opaque, high density 
polyethylene (HDPE) bottles containing 30 tablets. Each container will also be labeled in 
compliance with applicable regulatory requirement, including the FDA-required cautionary 
statement “Caution: New Drug-Limited by Federal (or United States) Law to Investigational 
Use”. 
 Product Storage and Stability 
VT-1598 must be stored in a secure location at a controlled room temperature of 15°C to 25°C 
(59°F to 77°F) and protected from light and moisture.  
Matching placebo tablets must be stored in a secure location at a controlled room temperature of 
15°C to 25°C (59°F to 77°F) and protected from light and moisture.  
 
Acquisition/Distribution 
VT-1598 will be provided by NQP 1598, Ltd. or its designee.  
Matching placebo will be provided by NQP 1598, Ltd, or its designee. 
Study products (VT-1598 and placebo) will be distributed through the DMID Clinical Material 
Services (CMS, Fisher BioServices) and shipped from the DMID CMS to the ICON CRU site 
upon request and approval by DMID.  


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Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/Investigational Product 
Only subjects enrolled in the study may receive study products, and only authorized site staff 
may supply or administer study products. The unblinded pharmacist or designee will prepare the 
study product.  
Subjects will take the study product on Day 1 as follows: 
Designated tablets of VT-1598 or placebo are taken in the morning by mouth after an overnight 
fast of at least 8 hours. The dose given will be the dose designated for that dosage cohort (see 
Table 1). In the nominal dose escalation, subjects will be administered the study product and 
remain in a fasting state for 4 hours post-dose. In the planned additional cohort to evaluate the 
impact of a meal on PK at a previously evaluated dose level, the subjects will fast overnight for 
at least 8 hours prior to the start of a high-fat, high-calorie meal which will be entirely consumed 
in less than 30 minutes. The dose of study product will be administered 30 minutes after the start 
of the meal. The dates and times of study product administration and meal start, and end times 
will be recorded in the subjects’ electronic Case Report Form (eCRF). Any subject who does not 
finish the meal within 30 minutes will not be dosed and will be replaced. 
Water consumption for all cohorts will be restricted from one hour prior to dosing to one hour 
after dosing.  Subjects will consume approximately 240 mL of ambient temperature water with 
the dose of study product.  An additional 120 mL of water, if needed by the subject to swallow 
multiple tablets, will be documented in the eCRF. Each subject dose is to occur with 5 minutes. 
Any deviations from the dosage schedule will be recorded. 
The planned final doses of VT-1598 or placebo for subjects in each cohort are described in Table 
1. Details regarding planned dosing are included in Section 3.1.2 Dosing Scheme and Duration 
of Study and in the MOP. 
 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
The United States Food and Drug Administration (FDA) requires accounting for the disposition 
of all investigational products. The Site Principal Investigator (PI) is responsible for ensuring 
that a current record of product disposition is maintained, and product is dispensed only at an 
official study site by authorized personnel as required by applicable regulations and guidelines. 
The Site PI will delegate to the Research Pharmacist responsibility for study product 
accountability. 


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The Research Pharmacist (or designee) will keep a record of the dates and amounts of study 
product received (including packing slips), the amount dispensed to study subjects, any amount 
destroyed, the amount unused, and temperature and storage conditions. Product accountability 
will be recorded by the Research Pharmacist on a Product Disposition Record or equivalent 
document with a separate accountability record for study product and placebo. The pharmacy 
records must be available for inspection by the DMID monitoring contractors and is subject to 
inspection by a regulatory agency (e.g., FDA) at any time. An assigned Study Monitor will 
review the pharmacy records. 
Unused investigational product will be stored in the Investigational Pharmacy until clinical trial 
accountability is completed. At study termination, all unused investigational product will be 
handled in accordance with the MOP following complete drug accountability and monitoring. 
Unused placebo will be handled in accordance with the MOP. 
 


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SELECTION OF SUBJECTS AND STUDY ENROLLMENT 
AND WITHDRAWAL 
Upon arrival to the clinic, subjects are checked for eligibility through the Verified Clinical Trials 
(VCT) process (after signing the IRB - approved VCT consent) and are then given the IRB 
approved consent and HIPPA forms.  After a presentation of the consent and when subjects 
indicate their desire to proceed, the subject is brought to a private room and given an opportunity 
to ask questions of the licensed nurse or MD delegated to perform consenting.  After signing 
consent, protocol procedures are executed. 
Study retention strategies will include education and explanation of the study schedule and 
procedures during Screening and Enrollment visits. In addition, reimbursements will be 
disbursed at specific time points during the study with the amount contingent on completing 
study procedures. Participating subjects will be reminded of visits ahead of time, and study staff 
will contact subjects who miss appointments to encourage them to return for completion of 
safety evaluations. 
 
Eligibility Criteria 
 Subject Inclusion Criteria 
Subjects may be entered in the study only if all the following criteria are met: 
1. Willing and able to provide written informed consent and authorization for use of protected 
health information; 
2. Willing and able to comply with protocol requirements, instructions, and protocol-stated 
restrictions (including confinement to the CRU) and is likely to complete the study as 
planned; 
3. Male or female subjects, 18-45 years of age (inclusive); 
4. Subject is in good health to be safely enrolled in this protocol as determined by medical 
history and physical exam. 
5. BMI of 18-35 kg/m
2, inclusive, and minimum weight of 50 kg; 
6. If a female participant is of childbearing potential*, she must use a highly effective 
contraceptive method† from 30 days before enrollment through the 3 months after dosing. 


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*A woman is considered of childbearing potential unless post-menopausal (subject is at least 50 years old and 
has history of ≥2 years without menses without other known or suspected cause and has a FSH level >40 IU/L), 
or permanently surgically sterilized. 
 
†A highly effective contraceptive method includes surgical sterilization methods such as tubal ligation, bilateral 
oophorectomy, salpingectomy, hysterectomy, or successful tubal obliteration (e.g., Essure®) with documented 
radiological confirmation test at least 90 days after the procedure, or long-acting reversible contraception 
(progestin-releasing subdermal implants, copper intrauterine devices (IUDs), levonorgesterel-releasing IUDs. 
 
7. Males* having sexual intercourse with women of childbearing potential must agree to 
consistent use of condoms from study product administration through 3 months after 
dosing**; 
* including vasectomized men 
** and must also agree to not donate sperm during this same time period 
8. Subject has adequate venous access for blood collection. 
 Subject Exclusion Criteria 
1. has a chronic condition that may increase risk to subject or interfere with endpoint 
assessment (e.g., liver disease, kidney disease, immunodeficiency). 
2. Chronic condition diagnosed within 90 days of the screening visit 
3. Unstable chronic disease* within 6 months of the screening visit 
*as defined by need for medical intervention that lead to a change in medications and/or required 
hospitalization, surgery/procedure, or ED/urgent care visit 
4. History of psychiatric condition that has required hospitalization in the last 5 years or patient 
is considered unstable by study investigator 
5. Any condition that in the opinion of the Investigator could significantly impact drug 
absorption, distribution, or elimination; 
6. Any out of normal range laboratory value* at screening or enrollment (Section 8.1 and 
Appendix B).  
*A laboratory value that is Grade 1 (with the exception of ALT, AST, Total bilirubin, hemoglobin or serum 
creatinine) will be allowed if not considered to be clinically significant by the investigator. 
7. Abnormal ECGs. See Section 7.1 Clinical Evaluations for exceptions; 
8. Electrocardiographic QTcF interval >430 msec for males and >450 msec for females at 
Screening; 
9. Positive test for antibodies to HIV-1, HIV-2, HBsAg, or HCV; 
10. Positive urine drug test.  The drugs that will be screened for includes amphetamines, 
barbiturates , cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines. 


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11. Female subject of childbearing potential who is pregnant*, lactating, or planning to become 
pregnant during the study period or 3 months after the final dose of study product; 
*Having a positive serum pregnancy test at the Screening Visit or any other specified time point prior to the 
dose of study product. 
12. Received any study product in a clinical trial within 30 days prior to Screening; 
13. Admitted or documented illicit drug use or alcohol abuse within 6 months prior to Screening 
or during their participation in the trial; 
14. Consumed alcohol within 72 hours of Day -1, until after the visit to the CRU on Day 14 or 
have a positive alcohol test at Screening or on admission to the CRU; 
15. Tobacco* use within 90 days prior to the Screening Visit or while a subject is enrolled in the 
study OR A positive urine drug test for cotinine;  
*Tobacco use includes vaping, smoking tobacco, the use of snuff and chewing tobacco, and other nicotine or 
nicotine- containing products. 
16. Use of prescription drugs within 14 days prior to the dose of study product with the exception 
of hormonal contraceptives, which are permitted throughout the study; 
17. Received any non-prescription medications, vitamins, or dietary supplements* within 7 days of 
dosing, unless prior approval is granted by both the Investigator and the Sponsor; 
*Excluded from this list is intermittent use of acetaminophen at doses of ≤2 g/day or ibuprofen ≤1200 mg/day. 
Herbal supplements must be discontinued 7 days prior to the dose of the study product. 
18. History of intolerance or hypersensitivity to azole antifungals; 
19. Blood donation or other significant blood loss within 60 days of screening and for the 
duration of the study; 
20. Inability or difficulty swallowing whole capsules/tablets and/or multiple capsules/tablets; 
21. Consumption of beverages and foods containing caffeine for 24 hours prior to Day -1 until 
discharge from the CRU on Day 4; 
22. Consumption of grapefruit, or juices containing grapefruit or Seville oranges within 7 days 
prior to the scheduled dose of the study product until after the visit to the CRU on Day 14;  
23. Subject has plans to enroll or is already enrolled in another clinical trial that could interfere 
with safety assessment of the investigational product at any time during the study period*;  
 
*Includes trials that have a study intervention such as a drug, biologic, or device 


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24. Having dietary restrictions that would preclude the subject from participating in either fed or 
fasting cohorts; 
25. Having sensitivity or allergy to aspirin. 
 Withdrawal from the Study, Discontinuation of Study Product, or Study 
Termination  
 Withdrawal from the Study or Discontinuation of the Study Product  
Subjects may voluntarily withdraw their consent for study participation at any time without 
penalty or loss of benefits to which they are otherwise entitled.   
An investigator may also withdraw a subject from receiving the study product for any reason. 
Follow-up safety evaluations will be conducted, if the subject agrees.  If a subject withdraws or 
is withdrawn prior to completion of the study, the reason for this decision must be recorded in 
the case report forms (CRFs). If a subject withdraws from the study, he/she may request 
destruction of any samples taken, and the Investigator must document this in the site study 
records and communicate this request to the Sponsor. However, the investigator will inform the 
subject that already collected data will be retained and analyzed even if the subject withdraws 
from this study.  
The reasons for withdrawal might include, but are not limited to the following: 
• 
Subject withdraws consent; 
• 
subject becomes noncompliant; 
• 
medical disease or condition, or new clinical finding(s) for which continued participation, in 
the opinion of the investigator might compromise the safety of the subject, interfere with the 
subject's successful completion of this study, or interfere with the evaluation of responses; 
• 
subject lost to follow-up; 
• 
request of primary care provider; 
• 
at the request of the IRB/IEC, FDA, or NIAID; 
• 
the subject’s well-being, based on the opinion of the investigator. 


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The investigator will inform the subject that already collected data will be retained and analyzed 
even if the subject withdraws from this study. Subjects will be informed that they have the right 
to withdraw from the study at any time for any reason without prejudice to their medical care. If 
the subject has received the study drug, data collected for withdrawn subjects will be evaluated 
for safety and PK. 
In all cases of withdrawal, the reason for withdrawal will be recorded. Subjects who receive any 
amount of study product and who are discontinued from the study will be asked to complete all 
Day 21 safety assessments including follow-up of any AEs prior to termination from the study.   
Lost to Follow Up 
The following actions must be taken in relation to a subject who fails to attend the clinic for a 
required study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible; 
• 
The site must counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether the subject wishes to and/or should continue in the study; 
• 
In cases where the subject is deemed ‘lost to follow-up’, the Investigator or designee must 
make every effort to regain contact with the subject (e.g., multiple telephone calls on 
various dates/time, a certified letter to the subject’s last known mailing address, or 
equivalent methods). These contact attempts should be documented in the subject’s medical 
record. 
• 
should the subject continue to be unreachable, only then will they be considered to have 
withdrawn from the study with a primary reason of “Lost to Follow-up”. 
 Early Withdrawal 
In the event that a subject is prematurely discontinued from the study after receiving any amount 
of the study product but prior to discharge from the CRU, the Unscheduled Visit (Section 6.7 
Unscheduled Study Visits) procedures should be performed prior to discharging the subject from 
the CRU. If a subject receives any amount of study product and is prematurely discontinued from 
the study after discharge from the CRU, but prior to the Day 21/End-of-Study visit, an attempt 
should be made to have the subject return to the CRU to perform the Unscheduled Visit (Section 
6.7 Unscheduled Study Visits) 


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 Subject Replacement 
Subjects who have not received any amount of study product and discontinue from participation 
may be replaced, as well as subjects who experience emesis within the first 12 hours following 
dosing.  
Subjects who complete Cohort 3 but are not eligible or withdraw prior to dosing for Cohort 6 
will be replaced.  The Cohort 6 replacement subjects will receive the same treatment as assigned 
to the Cohort 3 subject they are replacing. 
Additionally, the first subject in each cohort to discontinue from participation due to loss to 
follow up, after receiving any amount of study product, is not replaced; if more than one subject 
in any cohort discontinues participation, these subjects will be replaced. Replacement of any 
subject is at the discretion of the Investigator in consultation with the Sponsor.  Replacement 
subjects should be allocated to the same treatment as the subject they replaced.  
 Study Termination  
As DMID, FDA and NQP 1598, Ltd. may terminate the study in the interest of subject safety and 
welfare. In addition, DMID reserves the right to terminate the study at any time for any other 
reason. If DMID terminates the study, the PI, IRB, SMC, ISM, designated contractors of DMID, 
,NQP 1598, Ltd., and the FDA will be informed, activities will be closed, and a study report will 
be prepared.  
If the study is prematurely terminated by the sponsor, any regulatory authority, or the 
investigator for any reason, the investigator will promptly inform the study subjects and assure 
appropriate follow-up for the subjects. The investigator will provide a detailed written 
explanation of the termination to the IRB. 


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STUDY PROCEDURES 
 
Screening  
6.1.1 Day -28 to Day -2 (Screening) 
Subjects will be screened within 28 days prior to study product administration. A sufficient 
number of subjects will be screened to enroll 48 subjects in the study. After the subject has 
signed the IRB-approved ICF, the following evaluations will be performed as indicated in the 
Schedule of Study Procedures and Evaluations (Appendix A VT-1598 Schedule of Study 
Procedures and Evaluations) and as detailed in Section 7 Description of Clinical and Laboratory 
Evaluations: 
• 
Demographics (date of birth, sex, and ethnic origin); 
• 
complete medical/medication history to include all past illnesses, alcohol and 
tobacco/vaping, illicit drug use history (previous 6 months), and all other drugs/medications 
taken, including non- prescription and herbal products,(previous 30 days) prior to screening 
procedures; complete physical examination including vital signs (heart rate, blood pressure, 
oral temperature and respiration rate, taken after being at rest for at least 5 minutes), height, 
and weight (for BMI calculation). If abnormal, these measurements may be repeated once; 
within 15 minutes of the original assessment; 
• 
obtain 12-lead ECGs after at least 5 minutes in the supine position (triplicate readings, at 
least 1 minute apart within a 15-minute period) to assess heart rate, rhythm, and interval 
information such as RR, PR, QRS, QT, QTc and QTcF; 
• 
obtain blood samples for fasting (at least 8 hours) clinical chemistry, hematology, 
coagulation tests, serum pregnancy test [if female of childbearing potential], FSH [if female 
and post-menopausal], and immunology screen (serum HIV, HBsAg, and HCV antibodies); 
• 
obtain urine sample for urinalysis, drugs of abuse and cotinine;  
• 
obtain urine test for alcohol; 
• 
review of Inclusion/Exclusion criteria to determine eligibility for entry into the study; 
• 
consult about birth control methods, permitted/non-permitted medications, non-medications, 
dietary and activity restrictions. 


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Enrollment 
6.2.1 Day -1 (Admission to Clinic; approximately 24 hours prior to dosing) 
Eligible subjects will return to the CRU on Day -1, the day prior to dosing, will undergo baseline 
evaluations as indicated in the Schedule of Study Procedures and Evaluations (Appendix A 
VT-1598 Schedule of Study Procedures and Evaluations ) and as detailed in Section 7, 
Description of Clinical and Laboratory Evaluations,  Study Procedures/Evaluations: 
• 
Review inclusion/exclusion criteria; 
• 
confirm that subject adhered to dietary restrictions (no food/beverages containing alcohol 
for previous 72 hours or caffeine for the previous 24 hours; no grapefruit, grapefruit juice, 
or juices containing grapefruit, or Seville oranges for previous 7 days); see Section 5.2.1); 
• 
review and record prior concomitant medications and non-pharmacologic 
treatments/procedures history since Screening; 
• 
review any change in medical history since Screening; 
• 
complete a targeted physical examination (general appearance, heart, lungs, skin, and 
abdomen); 
• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes), and weight, BMI. If abnormal, these 
measurements may be repeated once, within 15 minutes of the original assessment; 
• 
obtain blood samples for baseline fasting (at least 8 hours) clinical chemistry, hematology, 
coagulation tests, serum pregnancy test [if female of childbearing potential]);  
• 
obtain urine sample for urinalysis, drugs of abuse (amphetamines, barbiturates, cocaine, 
opiates, cannabinoids, phencyclidine, and benzodiazepines) and cotinine;  
• 
obtain urine test for alcohol; 
• 
if screening criteria are satisfied, admit subject to CRU.  If screening criteria are not 
satisfied, the subject is then entered as a screening failure into the AdvantageEDCSM 
(Electronic Data Capture System, Emmes). 


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 Treatment Period 
6.3.1 Day 1 – Inpatient CRU 
Study product will be administered on the morning of Day 1.  Subjects are inpatients in the CRU 
and will undergo procedures as indicated in the Schedule of Study Procedures and Evaluations 
(Appendix A VT-1598 Schedule of Study Procedures and Evaluations) and as detailed in, 
Section 7 Description of Clinical and Laboratory Evaluations, listed below: 
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since admission to the CRU; 
• 
confirm that subject adhered to fasting requirements of at least 8 hours before the dosing 
(for fasted cohorts; fed cohort will receive dose 30 minutes after starting a high-fat, high 
calorie meal); 
• 
obtain baseline urine sample for PK analysis (t=0), to be taken any time within 6 hours prior 
to dose; 
• 
obtain baseline blood sample for PK analysis (t=0), to be taken a time within 60 minutes 
prior to the dose (for fasted cohorts; within 30 minutes prior to the start of the pre-dose meal 
for the fed cohort); 
• 
targeted physical examination (general appearance, heart, lungs, skin and abdomen) 
including pre-dose resting vital signs (heart rate, blood pressure, oral temperature and 
respiration rate, taken after being at rest for at least 5 minutes and anytime within 60 
minutes prior to dosing) (for fasted cohorts; within 30 minutes prior to the start of the 
pre-dose meal for the fed cohort);. If abnormal, these measurements may be repeated once 
within 15 minutes of the original assessment; 
• 
obtain 12-lead ECGs after at least 5 minutes in the supine position (taken pre-dose any time 
within 60 minutes prior to dosing for fasting cohorts and any time within 60 minutes prior to 
dosing for the fed cohort); triplicate readings, at least 1 minute apart within a 15-minute 
period); 
• 
administer study product.   For the nominal dose escalations (Cohorts 1-5), study drug will 
be administered in a fasting state and subjects will remain fasted for at least 4 hours post-
dose. In Cohort 6, the planned additional cohort to evaluate the effect of a meal on PK, the 
subjects will be fed a high-fat, high-calorie meal which will be entirely consumed in less 


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than 30 minutes. The dose of the study product will be administered 30 minutes after the 
start of the meal. 
Following the administration of study product, the following procedures will be performed. PK 
samples (blood and urine) will be obtained (after the ECGs and vital signs whenever possible if 
the times coincide with one another): 
• 
Obtain blood samples for PK analysis at 0.5 h (±5 min), 1 h (±10 min), 1.5 h (±10 min), 2 h 
(±10 min), 3 h (±10 min), 4 h (±10 min), 6 h (±10 min), 8 h (±10 min), 10 h (±10 min), 12 h 
(±10 min), and 14 h (±10 min) hours post-dose; 
• 
collect urine samples for PK analysis in the following intervals following study product 
administration on Day 1:  0-6, 6-12, 12-24, hours post-dose;    
• 
obtain post-dose (6 h [±10 min]) blood sample for possible use in future research studies, if 
applicable. See Section 9.3 Consent for Future Use of Stored Specimens and Data. Consent 
for Future Use of Stored Specimens and Data and Schedule of Procedures (Appendix A VT-
1598 Schedule of Study Procedures and Evaluations); 
• 
12-lead ECGs obtained after at least 5 minutes in the supine position; taken post-dose [4 
hours (+/-10 minutes)]; triplicate readings, at least 1 minute apart within a 15-minute 
period); 
• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes) at 1 h (±10 min), 2 h (±10 min), 4 h (±10 
min), and 8 h (±10 min), post-dose.  If abnormal, these measurements may be repeated once, 
within 15 minutes of the original assessment; 
• 
collect and record adverse events (AEs) and concomitant medications. 
 
Day 2 – Inpatient CRU 
Subjects are inpatients in the CRU and will undergo procedures as indicated in the Schedule of 
Study Procedures and Evaluations (Appendix A VT-1598 Schedule of Study Procedures and 
Evaluations) and as detailed in Section 7 Description of Clinical and Laboratory Evaluations,  
Study Procedures/Evaluations: listed below: 
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 1;  
• 
obtain blood samples for PK analysis at 24 h (±30 min), and 36 h (±30 min) post-dose; 


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• 
collect urine samples for PK analysis in the following intervals following study product 
administration on Day 1:  24-36, 36-48 hours post-dose;    
• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes) at 24 h (±30 min), post-dose.  If abnormal, 
these measurements may be repeated once, within 15 minutes of the original assessment; 
• 
collect and record adverse events (AEs). 
 Day 3 – Inpatient CRU 
Subjects are inpatients in the CRU and will undergo procedures as indicated in the Schedule of 
Study Procedures and Evaluations (Appendix A VT-1598 Schedule of Study Procedures and 
Evaluations) and as detailed in Section 7 Description of Clinical and Laboratory Evaluations. 
Study Procedures/Evaluations: listed below: 
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 2; 
• 
obtain blood sample for PK analysis at 48 h (±30 min) and 60 h (± 30 min) post-dose;  
• 
collect urine sample for PK analysis in the following interval following study product 
administration on Day 1:  48-60 hours post-dose;    
• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes) at 48 h (±30 min), post-dose.  If abnormal, 
these measurements may be repeated once, within 15 minutes of the original assessment; 
• 
collect and record adverse events (AEs).  
 Day 4 – Discharge from CRU 
Subjects are inpatients in the CRU and will undergo procedures as indicated in the Schedule of 
Study Procedures and Evaluations (Appendix A VT-1598 Schedule of Study Procedures and 
Evaluations) and as detailed in  Section 7 Description of Clinical and Laboratory Evaluations.  
Study Procedures/Evaluations: listed below, prior to discharge from CRU: 
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 3; 
• 
obtain blood sample for PK analysis at 72 h (±30 min) post-dose;  


DMID Protocol 17-0087 
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Safety and Pharmacokinetics of VT-1598                                                                                        
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• 
collect urine sample for PK analysis in the following interval following study product 
administration on Day 1:  60-72 hours post-dose;  
• 
obtain blood samples for fasting (at least 8 hours and prior to 10 AM ) clinical chemistry, 
hematology, and coagulation tests;  
• 
obtain urine sample for urinalysis;  
• 
targeted physical examination (general appearance, heart, lungs, skin and abdomen) 
including resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken at 72 hours (±30 min) post-dose and after being at rest for at least 5 minutes). If 
abnormal, these measurements may be repeated once, within 15 minutes of the original 
assessment; 
• 
12-lead ECGs obtained after at least 5 minutes in the supine position; taken at 72 hours (±30 
min) post-dose; triplicate readings, at least 1 minute apart within a 15-minute period; 
• 
collect and record adverse events (AEs); 
• 
review post-discharge instructions (including birth control methods, permitted/non-
permitted medications, non-medications, dietary and activity restrictions), and schedule 
follow-up visits; 
• 
discharge from CRU. 
 
Follow-up  
Subjects will return to the CRU within the window indicated for each follow-up timepoint and 
will undergo procedures as indicated in the Schedule of Study Procedures and Evaluations 
(Appendix A VT-1598 Schedule of Study Procedures and Evaluations) and as detailed in Section 
7 Description of Clinical and Laboratory Evaluations. Study Procedures/Evaluations: listed 
below: 
 
Day 7 ± 1   
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 4; 
• 
review any change in medical history since Day 4; 


DMID Protocol 17-0087 
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• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes). If abnormal, these measurements may be 
repeated once, within 15 minutes of the original assessment; 
• 
obtain blood sample for PK analysis at 144 (±24) hours post-dose;  
• 
obtain blood samples for fasting (at least 8 hours) clinical chemistry, hematology, and 
coagulation tests;  
• 
obtain urine sample for urinalysis;  
• 
collect and record adverse events (AEs); 
• 
review post-discharge instructions (including birth control methods, permitted/non-
permitted medications, non-medications, dietary and activity restrictions); 
• 
subjects are released from the CRU after all assessments and procedures are completed and 
instructed to return for further follow-up evaluation on Day 14. 
6.4.2 
Day 14± 1   
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 7; 
• 
review any change in medical history since Day 7; 
• 
obtain resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes). If abnormal, these measurements may be 
repeated once, within 15 minutes of the original assessment; 
• 
obtain blood sample for PK analysis at 312 (±24) hours post-dose;  
• 
obtain blood samples for fasting (at least 8 hours) clinical chemistry, hematology, and 
coagulation tests; 
• 
obtain urine sample for urinalysis;  
• 
collect and record adverse events (AEs); 


DMID Protocol 17-0087 
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Safety and Pharmacokinetics of VT-1598                                                                                        
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• 
review post-discharge instructions (including birth control methods, permitted/non-
permitted medications, non-medications, dietary and activity restrictions); 
• 
subjects are released from the CRU after all assessments and procedures are completed and 
instructed to return for final study visit on Day 21. 
6.5 
Final Study Visit 
6.5.1 Day 21 ± 2  
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since Day 14; 
• 
review any change in medical history since Day 14; 
• 
obtain 12-lead ECGs after at least 5 minutes in the supine position (triplicate readings, at 
least 1 minute apart within a 15-minute period) to assess heart rate, rhythm, and interval 
information such as RR, PR, QRS, QT, QTc and QTcF; 
• 
obtain blood sample for PK analysis at 480 (±48) hours post-dose; 
• 
obtain blood samples for fasting (at least 8 hours) clinical chemistry, hematology, 
coagulation and serum pregnancy test [if female of childbearing potential] tests;  
• 
obtain urine sample for urinalysis;  
• 
targeted physical examination (general appearance, heart, lungs, skin and abdomen) 
including resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes).  If abnormal, these measurements may be 
repeated once, within 15 minutes of the original assessment; 
• 
collect and record adverse events (AEs); 
• 
review post-study period instructions (including use of contraceptives and instructions to 
report pregnancy, should it occur, up to 3 months following dose of study drug). 


DMID Protocol 17-0087 
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Safety and Pharmacokinetics of VT-1598                                                                                        
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 Early Termination Visit  
The clinic will make every effort to perform all assessments outlined for the Final Study Visit 
(Day 21±2) if a subject is terminated prematurely from the study. All information collected will 
be documented in the study records including eCRF. 
 Unscheduled Study Visits  
Subjects will return to the CRU at the direction of the site investigator for follow-up and data 
from unscheduled visits or procedures (if any) will be captured in the EDC system. Safety 
assessments including the following onsite evaluations: AE, PE, and any other study procedures 
deemed necessary by the PI will be obtained. 
Subjects returning to the CRU for Unscheduled visit(s) may undergo procedures as indicated in 
the Schedule of Study Procedures and Evaluations (Appendix A VT-1598 Schedule of Study 
Procedures and Evaluations) and as detailed in Section 7 Description of Clinical and Laboratory 
Evaluations Study, Procedures/Evaluations: listed below: 
• 
Review and record any concomitant medications and non-pharmacologic 
treatments/procedures since last visit; 
• 
standard 12-lead ECG (recording in triplicates) to assess heart rate, rhythm, and interval 
information such as PR, QRS, QT, QTc and QTcF, obtained after at least 5 minutes in the 
supine position;  
• 
obtain blood samples for clinical chemistry, hematology, and coagulation tests; 
• 
obtain blood sample for PK analysis; 
• 
obtain urine sample for urinalysis.  
• 
targeted physical examination (general appearance, heart, lungs, skin and abdomen; 
additional evaluation will be targeted to the suspected organ system described in any AE.)    
including resting vital signs (heart rate, blood pressure, oral temperature and respiration rate, 
taken after being at rest for at least 5 minutes.  If abnormal, these measurements may be 
repeated once, within 15 minutes of the original assessment; 
• 
collect and record adverse events (AEs). 


DMID Protocol 17-0087 
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Safety and Pharmacokinetics of VT-1598                                                                                        
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Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or protocol-
specific MOP requirements.  The noncompliance may be either on the part of the subject, the site 
principal investigator, or the site personnel.  As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. 
These practices are consistent with ICH E6: 
4.5 
Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance and Quality Control, Section 5.1.1 
5.20 
Noncompliance, Sections 5.20.1, and 5.20.2. 
It is the responsibility of the site principal investigator and personnel to use continuous vigilance 
to identify and report deviations within five working days of identification of the protocol 
deviation, or within five working days of the scheduled protocol-required activity.  All 
deviations must be promptly reported to DMID per the SDCC protocol deviation reporting 
procedures. 
All protocol deviations, as defined above, must be addressed in study subject data collection 
forms.  A completed copy of the DMID Protocol Deviation Form must be maintained in the 
Regulatory File, as well as in the subject's chart.  Protocol deviations must be sent to the local 
IRB per their guidelines.  The site principal investigator and personnel are responsible for 
knowing and adhering to their IRB requirements. 


DMID Protocol 17-0087 
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DESCRIPTION OF CLINICAL AND LABORATORY 
EVALUATIONS 
 
Clinical Evaluations 
 Safety Tests and Assessments 
Safety assessments will include attention to relevant changes in the following parameters, which 
are identified as occurring after the start of study product, regardless of whether the change is in 
an examination finding, test result, or symptom(s) reported by a subject, and regardless of 
presumed relationship to VT-1598.  
Height, Weight, BMI 
Height and/or body weight will be collected at times specified in the Schedule of Assessments 
and Procedures Appendix A VT-1598 Schedule of Study Procedures and Evaluations. BMI is 
calculated from height at Screening and weight at time of assessment. 
Vital Signs 
Vital signs (resting) to include body temperature, heart rate (pulse), breathing rate, and blood 
pressure will be obtained at times specified in the Schedule of Assessments and Procedures 
Appendix A VT-1598 Schedule of Study Procedures and Evaluations. Vital signs should be 
taken after at least 5 minutes at rest. If abnormal, these measurements may be repeated once, 
within 15 minutes of the original assessment. 
The pre-dose Day 1 vital signs measurements should be taken any time within 60 minutes prior 
to dosing (within 30 minutes prior to the start of the pre-dose meal for the fed cohort). Day 1 
post-dose vital signs measurements should be taken within ± 10 minutes of the nominal 
timepoint. All other vital signs measurements during the inpatient stay should be taken within ± 
30 minutes of the nominal time point. For outpatient visits, vital signs measurements should be 
taken within the visit window. 
 
Physical Exam 
A complete physical examination will include review of resting vital signs (taken after being at 
rest for at least 5 minutes); general appearance; head, eyes, ears, nose, and throat; neck; chest and 
lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, 
and neurological system will be performed at Screening.   
A targeted physical examination (general appearance, heart, lungs, skin and abdomen) will 
include review of the resting vital signs which will be taken at 72 hours (±30 min) post-dose and 


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after being at rest for at least 5 minutes.  Additional evaluation will be targeted to the suspected 
organ system described in any AE. Targeted physical examinations will be performed at times 
specified in the Schedule Assessments and Procedures  Appendix A VT-1598 Schedule of Study 
Procedures and Evaluations . 
Electrocardiograms 
Standard 12-lead ECGs to assess heart rate, rhythm, and interval information such as PR, QRS, 
QT, and QTc will be obtained at times specified in the Schedule of Assessments and Procedures 
Appendix A VT-1598 Schedule of Study Procedures and Evaluations. The QT interval will be 
corrected using the Fridericia formula (QTcF).  
Electrocardiograms should be taken after at least 5 minutes in the supine position. The pre-dose 
Day 1 ECGs should be taken within 60 minutes prior to dosing (within 60 minutes prior to 
dosing for the fed cohort); the post-dose ECG on Day 1 should be taken at 4 hours post-dose ( ± 
30 minutes).  The Day 4 ECG should be taken at 72 hours (± 30 minutes) post-dose.  For the Day 
21 outpatient visit, the ECG should be taken within the visit window. 
Subjects will be placed in a supine position for at least 5 minutes prior to recording an ECG. 
Triplicate 12- lead ECG readings will be collected at scheduled times as shown in Appendix A 
VT-1598 Schedule of Study Procedures and Evaluations . The screening ECG will be used by 
the PI to determine subject’s eligibility for enrollment. The Day 1 pre-dose ECG will be 
reviewed to determine if subjects are safe and appropriate to dose and will be used to determine 
baseline for waveform and QTc. 
All ECGs will be reviewed by the PI or designee. ECGs with the following readings will be 
considered acceptable for study and will not be considered abnormal for study purposes unless 
the PI or physician designee believes they represent a new medical condition when compared to 
baseline ECGs. In such cases an AE will be documented, and the subject will be followed for 
safety evaluations as appropriate. The following pre-existing conditions identified at enrollment 
will not be considered adverse events and will be documented on the Medical History eCRF: 
• 
Sinus bradycardia; 
• 
Sinus arrhythmia. 
Subjects without a history of prolonged QTc and an abnormal baseline QTcF interval (not 
meeting exclusion criteria) should undergo repeat ECG assessment within screening period prior 
to randomization to confirm prolongation. If the repeat ECG QTcF is within normal limits the 
subject may be considered for enrollment 


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The Sponsor may review all or individual screening or Day 1 ECGs or may delegate to PI 
determine if meets intention of entry criteria goal of enrolling healthy normal study subjects. 
The mean of triplicate QTcF measurements post-dose will be used to assess QTcF prolongation 
(including assessment of halting rules described in Section 8.6), and will be compared to the 
mean of the baseline measurements to calculate change from baseline. 
In the event of a prolongation of QTc post dosing, the site will start telemetry monitoring of the 
subject and capture triplicate 12 lead ECG (3 tracings within a 5-minute period) every 30 
minutes (±10 minutes) until the average for the triplicates has returned within 60ms of the 
baseline value at which time telemetry maybe discontinued. Persistent (1 hour or more) elevation 
in QTcF (>500ms) should prompt immediate consideration of transfer to appropriate emergency 
department for further evaluation, monitoring, and/or treatment. 
In the event of a change in ECG wave forms consistent with a change in cardiac function or 
conduction when compared to baseline tracings, or in the event of a subject with possible cardiac 
related symptoms, repeat ECG should be obtained every 30 minutes (±10 minutes) until wave 
form change reverts to baseline appearance, or symptoms resolve, or are determined not to be 
cardiac in origin. Subjects with cardiac related symptoms associated with ECG changes will be 
transferred to appropriate emergency department for further evaluation and treatment. 
 
Assessment of Concomitant Medications/Treatments other than Study Product 
Prohibited Medications/Non-Medications 
Subjects are required to abide by the following rules regarding intake of medications and other 
substances before and during the study: 
• 
Refrain from the use of all prescription medications (with the exception of hormonal 
contraceptives), including any type of prescription antibiotic drug (topical or systemic) for 
at least 14 days prior to administration of the dose of study product on Day 1 until after the 
final study visit to the CRU; 
• 
refrain from the use of all non-prescription medications, vitamins, or dietary supplements, 
within 7 days prior to administration of the dose of study product on Day 1 until after the 
visit to the CRU on Day 14; 
• 
herbal supplements must be discontinued 7 days prior to the dose of study product on Day 1 
until after the visit to the CRU on Day 14; 


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• 
the consumption of beverages and foods containing alcohol is prohibited for 72 hours prior 
to Day -1 until after the visit to the CRU on Day 14. A urine alcohol test will be performed 
at Screening and upon admission to the CRU; 
• 
the consumption of beverages and foods containing caffeine is prohibited for 24 hours prior 
to Day -1 until discharge from the CRU on Day 4; 
• 
consumption of grapefruit, grapefruit juice, or juices containing grapefruit, or Seville 
oranges is prohibited within 7 days prior to the dose of study product until after the visit to 
the CRU on Day 14; 
• 
the use of tobacco product, including smoking and the use of snuff and chewing tobacco, 
and other nicotine or nicotine-containing products, is not permitted by a subject within 90 
days of Screening for the study or while a subject is enrolled in the study. A urine test for 
cotinine will be performed at Screening and upon admission to the CRU; 
• 
the use of illegal drugs is not permitted while a subject is enrolled in this study. A urine drug 
test, including amphetamines, barbiturates, cocaine, opiates, phencyclidine, cannabinoids 
and benzodiazepines, will be performed at Screening and upon admission to the CRU. 
If a subject is unable to comply with the restrictions described above, the subject’s continued 
participation in the study will be re-evaluated by the Investigator, in consultation with the 
Medical Monitor. 
Permitted Medications/Non-Medications 
Medications to treat any AEs the subject experiences during the study are permitted at the 
Investigator’s discretion and/or in consultation with the Medical Monitor. Intermittent use of 
acetaminophen at doses of ≤ 2 g/day or ibuprofen ≤1200 mg/day is allowed throughout the study. 
Hormonal contraceptives are permitted throughout the study. 
Meals and Dietary Restrictions/Dosing Under Fasting Conditions 
Subjects will fast overnight for at least 8 hours prior to dosing on Day 1. Subjects will remain 
fasted until at minimum 4 hours after dosing, at which time lunch may be consumed. Other 
meals will be supplied at appropriate times thereafter while subjects are resident in the unit. 
Food Impact Evaluation Under Fed Conditions 
Subjects will fast overnight for at least 8 hours prior to the start of a high-fat, high-calorie meal 
which will be entirely consumed in less than 30 minutes. The dose of VT-1598 will be 
administered 30 minutes after the start of the meal (defined as the time when the first bite of the 


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meal is taken) with 8 ounces (240 mL) of water. The high-fat, high-calorie test meal will be 
comprised of a breakfast of approximately 900-1000 calories, with approximately 150 calories 
from protein, 250 calories from carbohydrates, and 500-600 calories from fat (an example of a 
high-fat, high-calorie breakfast is: 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with 
butter, 4 ounces of hash brown potatoes fried with butter and 8 ounces or 240 mL of whole 
milk). No other food will be ingested until after a minimum of 4 hours after dosing, at which 
time lunch may be consumed. Water can be allowed as desired except for one hour before and 
after drug administration. Other meals will be supplied at appropriate times thereafter while 
subjects are resident in the unit. 
Exercise 
Subjects will be prohibited from engaging in strenuous activity within 48 hours prior to dosing 
and should be discouraged from engaging in strenuous activity within 48 hours prior to returning 
to the CRU on Days 7, 14, and 21 Subjects will not engage in strenuous activity at any time 
during the confinement period. Walking at a normal pace will be permitted. 
 Assessment of Subject Compliance with Study Intervention/Investigational 
Product/Investigational Device  
Subjects will be directly observed at the time of dosing by a member of the clinical research 
team who is licensed to administer the study product. Study personnel will examine the oral 
cavity of each subject following each dose to assure that all study product was swallowed. 
Administration will be documented and entered into the eCRF. 
 
Laboratory Evaluations 
 Clinical Laboratory Evaluations 
All laboratory assessments will be done by the clinical site’s certified laboratory. Laboratory 
toxicity grading will be determined by use of the FDA Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials September 2007 and the Division of Microbiology and Infectious Diseases (DMID) Adult 
Toxicity Table November 2007, as modified for this study and appropriate for the administration 
of VT-1598 (Appendix B VT-1598 Toxicity Grading Criteria for Normal Human Subjects). 
At Screening and at baseline, laboratory test values that fall outside the reference range on the 
laboratory reports and deemed not clinically significant by the Investigator may be repeated at 
the discretion of the Investigator (to assess for transitional conditions). A laboratory value that is 
Grade 1 (with the exception of ALT, AST, Total bilirubin, hemoglobin or serum creatinine) will 
be allowed if not considered to be clinically significant by the investigator 


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If a single repeat Screening evaluation or baseline is within the reference range, the subject may 
be further considered for study eligibility Note: Hematuria during active menses causing 
urinalysis results outside the reference range will not be considered clinically significant (not an 
AE). Post-dose serum cortisol levels Grade 2 or greater must be repeated and if confirmed, then 
an ACTH stimulation test should be performed. 
*See Appendix B VT-1598 Toxicity Grading Criteria for Normal Human Subjects. 
Pregnancy Testing 
All women of childbearing potential must undergo serum pregnancy testing at Screening and 
Baseline to assess protocol eligibility. Serum pregnancy tests will be performed thereafter as 
specified in the Schedule of Assessments and Procedures. Appendix A VT-1598 Schedule of 
Study Procedures and Evaluations 
Female subjects reporting as post-menopausal must undergo testing for serum FSH levels to 
assess childbearing potential at Screening. 
Immunology 
All subjects must undergo testing for the detection of antibodies to HIV-1 and HIV-2, HBsAg, 
and antibodies to HCV at Screening to assess protocol eligibility. 
Clinical Chemistry Panel 
All subjects must undergo clinical chemistry testing (albumin, glucose, blood urea nitrogen or 
urea, potassium, calcium, sodium, chloride, total protein, creatinine, triglycerides, total 
cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total carbon 
dioxide, creatine phosphokinase, phosphorus, magnesium, gamma-glutamyl transferase (GGT), 
alkaline phosphatase, AST, ALT, total bilirubin, direct bilirubin and serum cortisol) at Screening 
and Baseline to assess protocol eligibility. Clinical chemistry tests will be performed thereafter 
as specified in the Appendix A Schedule of Assessments and Procedures. Subjects must fast a 
minimum of 8 hours before blood collection for a clinical chemistry panel. Serum cortisol levels 
must be drawn prior to 10 a.m. 
Hematology and Coagulation 
All subjects must undergo hematology (red blood cell count, total and differential white blood 
cell counts, hemoglobin, hematocrit, and platelet count) and coagulation (activated partial 
thromboplastin time, prothrombin time, and international normalized ratio) testing at Screening 
and Baseline to assess protocol eligibility. Hematology and coagulation tests will be performed 
thereafter as specified in the Appendix A Schedule of Assessments and Procedures.    


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Urinalysis 
All subjects must undergo urinalysis testing (leukocyte esterase, blood, pH, and specific gravity 
[microscopic tests to be completed if dipstick urinalysis is abnormal]) at Screening and Baseline 
to assess protocol eligibility. Urinalysis testing will be performed thereafter as specified in the 
Appendix A Schedule of Assessments and Procedures. 
 Research Assays  
Plasma and urine samples will be analyzed to determine concentrations of VT-1598 and VT-
11134 using validated liquid chromatography/tandem mass spectrometry methods by the 
bioanalytical contractor, ICON BAL.  
Analytical Sample Collection and Handling 
Blood samples for the determination of VT-1598 and VT-11134 plasma concentrations will be 
collected as shown in Table 2:  
Table 2: Blood PK Sampling Timepoints 
Blood Sampling Timepoints for VT-1598 and VT-11134 Pharmacokinetic Analyses 
Day 1 (pre-dose) 
Cohorts 1-5 (fasting):  Taken within 60 minutes prior to dosing 
Cohort 6 (fed):  Taken within 30 minutes prior to start of pre-dose 
meal. 
Day 1 (hours post 
dose*) 
0.5  
1 
1.5 
2 
3 
4 
6 
8  
10 
12 
14 
Day 2 (hours post 
dose**) 
24 
36 
 
Day 3 (hours post 
dose**) 
48 
60 
 
Day 4 (hours post 
dose**) 
72 
 
Day 7 (hours post 
dose)*** 
144 
 
Day 14 (hours post 
dose)*** 
312 
 
Day 21 (hours post 
dose)*** 
480 
 
*The 0.5-hour post dose blood sample should be taken within ± 5 minutes of the nominal 
timepoint.  The remaining post dose blood samples on Day 1 should be taken within ± 10 
minutes of the nominal time points.  


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**The post dose blood samples during the inpatient stay should be taken within ± 30 minutes of 
the nominal time point on Days 2, 3 and 4. 
***For outpatient visits, blood samples should be taken within the visit window. 
The exact dates and times of blood collection must be recorded in the eCRF and source 
documents. The blood samples will be obtained via direct venipuncture or via indwelling 
intravenous catheter using saline flushes to maintain catheter patency. Specific details for blood 
sample collection, process blood to plasma, and sample handling are included in the MOP for 
this study. 
Urine samples for the determination of VT-1598 and VT-11134 amounts will be collected in the 
intervals shown in Table 3: 
Table 3: Urine PK Sampling Timepoints 
Urine Sampling Timepoints for VT-1598 and VT-11134 Pharmacokinetic Analyses 
Day 1 (pre-dose) 
Collected from -6 hours until 0 hours pre-dose (For fasted 
cohorts) 
Day 1 (hours post dose) 
0-6 
>6-12 
>12-24 
Day 2 (hours post dose) 
24-36 
36-48 
 
Day 3 (hours post dose) 
48-60 
60-72 
 
The exact dates, start and stop time for each intervals and volumes of urine collection must be 
recorded in the eCRF and source documents.  For each interval, volume will be measured, and an 
aliquot will be retained and analyzed for the determination of VT-1598 urine concentrations. 
Specific details for urine specimen collection and handling are included in the MOP for this 
study. 
Laboratory Specimen Preparation, Handling, and Storage 
Detailed instructions for plasma and urine specimen preparation, handling and storage are 
outlined in the MOP for this study. 
Total Blood Volume Drawn   
The total volume of blood that will be drawn from each subject is described in Table 4. 
Table 4: Total Volume of Blood Drawn From Each Subject 
Type 
Laboratory Test 
Sample Volume 
(mL) 
Number of 
Samples 
Total Volume 
(mL) 


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Safety: 
Clinical chemistry 
3.5 
7 
24.5 
Cortisol 
3.5 
7 
24.5 
Hematology 
2 
7 
14 
Coagulation 
2.7 
7 
18.9 
Serology 
4 
1 
4 
future assays[a] 
6 
1 
6 
Pharmacokinetic: 
3 
20 
60 
When using an indwelling catheter 1.0 mL of blood will be removed prior to sample collection 
Total 
24.7 
50 
151.9 
[a] EDTA Blood sample will be collected 6 hours post-dose; plasma will be processed and stored 
to allow for the option to test for additional parameters. See Section 9.3 Consent for Future Use 
and Storage of Specimens.  
 
Laboratory Specimen Shipping 
All PK and future use specimens will be shipped to the Fisher Biorepository for storage and/or 
transfer to the ICON BAL.  Detailed instructions for shipping plasma and urine samples are 
outlined in the MOP for this study.   


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ASSESSMENT OF SAFETY 
 
Assessing and Recording Safety Parameters 
Safety will be assessed by collection of AEs, physical examinations, clinical laboratory results, 
vital signs, and ECG from time of dosing until final visit. 
 Adverse Events (AEs) 
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product regardless of its causal relationship to the study 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product. The occurrence of an AE may come to the attention of study personnel 
during study visits and interviews of a study recipient presenting for medical care, or upon 
review by a study monitor. 
All adverse events should be captured on the appropriate eCRF. Information to be collected 
includes event description, date of onset, clinician’s assessment of severity, relationship to study 
product (assessed only by those with the training and authority to make a diagnosis and listed on 
the Form FDA 1572 as an investigator) date of resolution/stabilization of the event, outcome and 
severity. All AEs occurring while in study must be documented appropriately regardless of 
relationship. All AEs will be followed to resolution/stabilization. 
Any medical or laboratory condition that is present at the time that the subject is screened up 
through ingestion of the dose should be considered as baseline/pre-existing condition and not 
reported as an AE. However, if it deteriorates at any time during the study after ingestion of the 
dose, it should be recorded as an AE. 
Adverse Events Grading 
AEs will be assessed by a licensed study physician listed on the Form FDA 1572 as the site 
principal investigator or appropriate sub-investigator using a protocol-defined grading system. 
For events not included in the protocol-defined grading system (Section 8 Assessment of 
Safety/Appendix B VT-1598 Toxicity Grading Criteria for Normal Human Subjects), the 
following guidelines will be used to quantify severity:  
• 
• Mild (Grade 1): Events require minimal or no treatment and do not interfere with the 
subject’s daily activities;  


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• 
• Moderate (Grade 2): Events result in a low level of inconvenience or concern with 
therapeutic measures. Moderate events may cause some interference with functioning and 
daily activities and use of over the counter medication;  
• 
• Severe (Grade 3): Events interrupt the subject’s usual daily activities and may require 
systemic drug therapy or other treatment. Severe events are usually incapacitating. 
Relationship to Study Products: The assessment of the relationship of an AE to the 
administration of study product is made only by those with the training and authority to make a 
diagnosis and listed on the Form FDA 1572 as an investigator based on all available information 
at the time of the completion of the eCRF.  Whether the AE is related or not, is not a factor in 
determining what is or is not reported in this trial.  If there is any doubt as to whether a clinical 
observation is an AE, the event should be reported.   
In a clinical trial, the study product must always be suspect.  To help assess, the following 
guidelines are used. 
• 
Related – There is a reasonable possibility that the study product caused the adverse event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between 
the study product and the adverse event; 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event. 
 Serious Adverse Events (SAEs) 
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
• 
Death; 
• 
a life-threatening adverse event1; 
• 
inpatient hospitalization or prolongation of existing hospitalization; 
• 
a persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions, or;  
• 
a congenital anomaly/birth defect;   
• 
important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical judgment 
they may jeopardize the patient or subject and may require medical or surgical intervention to 


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prevent one of the outcomes listed in this definition.  Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
1 Life-threatening adverse event. An adverse event is considered “life-threatening” if, in the view 
of either the site principal investigator or sponsor, its occurrence places the patient or subject at 
immediate risk of death.  It does not include an adverse event, had it occurred in a more severe 
form, might have caused death. 
SAEs will be: 
• 
Assessed for severity and relationship to study product and alternate etiology (if not related 
to study drug); 
• 
recorded on the appropriate SAE data collection form and eCRF; 
• 
followed through resolution; 
• 
reviewed and evaluated by an Independent Safety Monitor (ISM) (as deemed necessary), the 
SMC (periodic review unless related), DMID, and the IRB; 
SAEs will be followed until resolution even if this extends beyond the study-reporting period.  
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic.  
 
Specification of Safety Parameters 
 Dose Escalation Criteria 
The initial cohort of 8 subjects will be administered 40 mg of VT-1598 (6 subjects) or placebo (2 
subjects) as a single oral dose. Two sentinel subjects will be included in Cohorts 1-5 as described 
in Section 4.2 Acquisition/Distribution. 
Dose escalation to each successive cohort of subjects will occur if none of the predefined dose 
escalation halting criteria are met (for all subjects through Day 7). Emmes will provide 
notification to the PI upon analysis of data for the cohort (for all subjects through Day 7) for 
halting criteria as described in Section 3 Study Design, Objectives and Endpoints or Outcome 
Measures, Dose Escalation. If any of the criteria for dose escalation are met, or, at the discretion 
of the PI or DMID Medical Monitor, the study enrollment and dosing will be stopped until the 


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SMC reviews the data and provides its recommendations. There will be a scheduled SMC data 
review meeting prior to start of Cohort 5.  
The nominal dose- escalation scheme will be 40, 80, 160, 320 and 640 mg) or matching placebo 
administered in a fasting state. The effect of a high-fat, high-calorie meal on the PK of VT-1598 
is planned in an additional cohort that will be dosed at 160 mg.  The fed cohort will be dosed at 
160 mg, after the 320 mg fasted cohort has been dosed. This provides additional safety data to 
cover the possibility that the bioavailability of VT-1598 is increased in the presence of food 
under the fed state. The highest proposed dose in this study is 640 mg, which is 53% of the body 
surface area equivalent of the NOAEL in the most sensitive species.   
 Reporting Serious Adverse Events 
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at the 
following address:  
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
In addition to the SAE form, select SAE data fields must also be entered into Advantage EDC. 
Please see the protocol-specific MOP for details regarding this procedure.  
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible.  
The site will send a copy of the SAE report(s) to the ISM (as deemed necessary) when they are 
provided to the DMID Pharmacovigilance Group.  The DMID Medical Monitor and DMID 
Clinical Project Manager will be notified of the SAE by the DMID Pharmacovigilance Group.  
The DMID Medical Monitor will review and assess the SAE for regulatory reporting and 
potential impact on study subject safety and protocol conduct. 
At any time after completion of the study, if the site principal investigator or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the site 


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principal investigator or appropriate sub-investigator will report the event to the DMID 
Pharmacovigilance Group.  
 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND 
Following notification from the investigator, DMID, the Investigational New Drug (IND) 
sponsor, will report any suspected adverse reaction that is both serious and unexpected.  DMID 
will report an adverse event as a suspected adverse reaction only if there is evidence to suggest a 
causal relationship between the drug and the adverse event.  DMID will notify FDA and all 
participating investigators (i.e., all investigators to whom the sponsor is providing drug under its 
IND(s) or under any principal investigator’s IND(s) and NQP 1598, Ltd. in an IND safety report 
of potential serious risks from clinical trials or any other source, as soon as possible, but in no 
case later than 15 calendar days after the sponsor determines that the information qualifies for 
reporting as specified in 21 CFR Part 312.32.  DMID will also notify FDA of any unexpected 
fatal or life-threatening suspected adverse reaction as soon as possible, but in no case later than 7 
calendar days after the sponsor’s initial receipt of the information.  Relevant follow up 
information to an IND safety report will be submitted as soon as the information is available.  
Upon request from FDA, DMID will submit to FDA any additional data or information that the 
agency deems necessary, as soon as possible, but in no case later than 15 calendar days after 
receiving the request. 
All serious events designated as “not related” to study product(s), will be reported to the FDA at 
least annually in a summary format. 
 Reporting of Pregnancy 
A Notification of Pregnancy form will be completed for any female study subject or for any 
female partner of a male study subject who becomes pregnant following their exposure to study 
product (Day 1) through 3 months after the dose of study product. The site will discuss 
pregnancy reporting with subjects at the Final Study visit with instructions and provide contact 
information in case pregnancy occurs.  The pregnant subject will be followed by monthly 
telephone calls until 2 months after the birth of the baby or until the end of the pregnancy (in 
case pregnancy is terminated) at which time the Pregnancy Outcome form will be completed. 
Infants born to these study subjects will also be monitored for SAEs for up to 2 months after 
birth (information regarding SAEs will be captured on the Pregnancy Outcome form and the 
SAE form). If an SAE occurs during the pregnancy, the SAE will be reported on the appropriate 
SAE form and provided to DMID pharmacovigilance. Pregnancy Outcome forms will be used to 
collect, but not be limited to, data on the following information, should it be identified during the 
monthly telephone calls, at the end of the pregnancy, or at the follow-up telephone call at 2 
months after birth of the baby: 


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1. 
Prior maternal history including congenital abnormalities or pregnancy 
complications; 
2. 
estimated date of conception; 
3. 
estimated and actual date of delivery or pregnancy termination; 
4. 
mode of delivery; 
5. 
maternal complications; 
6. 
neonatal complications (i.e. lethal or nonlethal congenital abnormality). 
 
Type and Duration of Follow-up of Subjects after Adverse Events 
All AEs will be followed until resolution even if this extends beyond the study-reporting period.  
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic.  
 
Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings 
Abnormal laboratory values, performed as part of hematology, chemistry panel, or urinalysis but 
not listed in Appendix B, VT-1598 Toxicity Grading Criteria for Normal Human Subjects,  will 
be evaluated by the study clinicians, recorded in the source document and, if clinically 
significant, considered AEs and graded according to the criteria details described in Section 8.1 
Assessing and Recording Safety Parameters.  
The site principal investigator or appropriate sub-investigator is responsible for recording all AE 
and SAEs that are observed or reported during this study, regardless of the relationship to study 
product.  AE and SAEs or abnormal clinical findings will be collected, assessed, documented, 
reported, and followed appropriately. 
 
Halting Rules 
 Study Halting Criteria 
If any of the criterion below are met, the study will be suspended (enrollment and dosing), and 
the SMC ad hoc meeting will convene:  
• 
Any SAE, regardless of the relationship to the study drug, throughout duration of study, 
unless confirmed to be of reasonable alternative etiology. 


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• 
5 or more subjects in study (cumulative among all cohorts) experience a same grade 2 (or 
higher) related AE (laboratory or systemic) which is coded in the same high-level group 
term (HLGT) per MedDRA coding, throughout duration of study. 
 Dose Escalation Halting Criteria 
Sentinel Subject Halting Rules  
If any of the criterion below are met, the cohort will be suspended (enrollment and dosing), and 
the SMC ad hoc meeting will convene:  
• 
Any SAE (regardless of the relationship to the study drug) through Day 3 of the study; 
• 
any Grade 2 (or higher) adverse event (laboratory or systemic) if not resolved within 1 day, 
through Day 3 of the study. 
Cohort Dose Escalation Halting Rules  
If any of the criterion below are met, the escalation to the next cohort will be suspended 
(enrollment and dosing), and the SMC ad hoc meeting will convene.  
• 
2 or more subjects in a cohort experience the same grade 2 (or higher) related AE 
(laboratory or systemic) which is coded in the same HLGT per MedDRA coding, through 
Day 7 of the study; 
• 
2 or more subjects within a cohort with post-dose QTcF > 500 ms or change from baseline 
>60 ms through Day 7 of the study. 
 
Safety Oversight 
 Independent Safety Monitor (ISM) 
An ISM is a physician with relevant expertise whose primary responsibility is to provide to 
DMID an independent safety assessment in a timely fashion. This ISM is identified by the 
investigator site and approved by DMID. Participation is for the duration of the DMID study and 
is a voluntary position that does not receive payment. The ISM must meet the requirements of 
the NIAID conflict of interest policy.   
The ISM: 
• 
Is in close proximity to the study site and has the authority and ability to readily access 
study participant records in real time; 


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• 
may be a member of the participating institution’s staff but preferably be from a different 
organizational group within the institution; 
• 
should not be in a direct supervisory relationship with the investigator; 
• 
should have no direct involvement in the conduct of the study. 
The ISM will: 
• 
Sign a Conflict of Interest (COI) certification at the time they are asked to participate and 
provide updates to this information as needed; 
• 
receive reports of Serious Adverse Events (SAEs) from the site investigator;  
• 
evaluate the SAE and report their clinical assessment to DMID, through DMID-CROMS 
SOCS in a timely manner using the AE form and email the report to DMID-CROMS SOCS;  
• 
communicate with the investigator at the participating site as needed; 
• 
review additional safety related events at the request of DMID; 
• 
provide additional information to DMID and/or the DSMB by teleconference as requested. 
 Safety Monitoring Committee (SMC) 
The SMC is an independent group of experts (at least 3 members) that monitors subject safety 
and advises DMID. SMC members will be separate and independent of study personnel 
participating in this study and should not have scientific, financial, or other conflicts of interest 
related to the study. The SMC will consist of members with appropriate expertise to contribute to 
the interpretation of the data from this trial. A quorum will consist of a simple majority.  
The SMC will review the safety data at the following timepoints: 
• 
Organizational meeting (prior to start of the study); 
• 
data review meeting; 
• 
between Cohorts 4 and 5;  
• 
scheduled meeting upon completion of dosing and final visit for all cohorts; 
• 
ad hoc meeting(s)  


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o When a halting criterion is met for sentinels, dose escalation or the overall study;  
o at the request of DMID to review a potential safety concern identified by the 
either the PI, DMID medical monitor, participating investigator, or the ISM. 
Procedures for SMC reviews/meetings will be defined in the SMC charter. The SMC will review 
applicable data to include, but not limited to, enrollment, demographic, dosing, laboratory, and 
safety data at scheduled time points during the study as defined in the charter. The SMC will 
receive data in aggregate. The SMC may request to receive data by study product vs placebo in a 
closed session. The SMC may also request that the blind be broken for individual subjects, as 
needed, to assess safety issues. As an outcome of each review/meeting, the SMC will make a 
recommendation in writing to continue, modify, or terminate the study. 
 


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HUMAN SUBJECTS PROTECTION 
 
Institutional Review Board/Independent Ethics Committee 
The site principal investigator will obtain IRB approval for this protocol to be conducted at his 
research site and send supporting documentation to the DMID before initiating recruitment of 
subjects.  The investigator will submit applicable information to the IRB on which it relies for 
the review, to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, and as 
applicable, 21 CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human 
Subjects), other federal, state, and local regulations. DMID must receive the documentation that 
verifies IRB-approval for this protocol, associated informed consent documents, and upon 
request any recruitment material and handouts or surveys intended for the subjects, prior to the 
recruitment and enrollment of subjects.     
Any amendments to the protocol or consent materials will be approved by the IRB before they 
are implemented.  IRB review and approval will occur at least annually throughout the 
enrollment and follow-up of subjects and may cease if annual review is no longer required by 
applicable regulations.  The investigator will notify the IRB of deviations from the protocol and 
reportable SAEs, as applicable to the IRB policy. 
 
Informed Consent Process 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation.  Before any study procedures 
are performed, informed consent will be obtained and documented.  Subjects will receive a 
concise and focused presentation of key information about the clinical trial, verbally and with a 
written consent form. The explanation will be organized and presented in lay terminology and 
language that facilitates understanding why one might or might not want to participate. 
The site principal investigator or designee will describe the protocol to potential subjects face-to-
face. The key information about the purpose of the study, risks and discomforts, and any 
potential benefits to society will be presented first to the subject.   
Subjects will also receive an explanation that the trial involves research, and a detailed summary 
of the proposed study procedures and study interventions/products.  This will include the 
probability for random assignment to treatment groups, all possible risks (including a statement 
that the particular treatment or procedure may involve risks to the subject or to the embryo or 
fetus, if the subject is or may become pregnant, that are currently unforeseeable), and the 
expected duration of the subject’s participation in the trial. 


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Subjects will be informed that they will be notified in a timely manner if information becomes 
available that may be relevant to their willingness to continue participation in the trial. Subjects 
will receive an explanation as to whether any compensation and any medical treatments are 
available if injury occurs, and, if so, what they consist of, or where further information may be 
obtained. Subjects will be informed of the anticipated financial expenses, if any, to the subject 
for participating in the trial, as well as any anticipated prorated payments, if any, to the subject 
for participating in the trial. They will be informed of whom to contact (e.g., the investigator) for 
answers to any questions relating to the research project.  
Information will also include the foreseeable circumstances and/or reasons under which the 
subject’s participation in the trial may be terminated. The subjects will be informed that 
participation is voluntary and that they are free to withdraw from the study for any reason at any 
time without penalty or loss of benefits to which the subject is otherwise entitled.   
The extent of the confidentiality of the subjects’ records will be defined, and subjects will be 
informed that applicable data protection legislation will be followed. Subjects will be informed 
that the monitor(s), auditors(s), IRB, NIAID, and regulatory authority(ies) will be granted direct 
access to the subject’s original medical records for verification of clinical trial procedures and/or 
data without violating the confidentiality of the subject, to the extent permitted by the applicable 
laws and regulations, and that, by signing a written informed consent form, the subject is 
authorizing such access.  
Subjects will be informed that records identifying the subject will be kept confidential, and, to 
the extent permitted by the applicable laws and/or regulations, will not be made publicly 
available and, if the results of the trial are published, the subject’s identity will remain 
confidential. Subjects will be informed whether private information collected from this research 
and/or specimens may be used for additional research, even if identifiers are removed.   
Subjects will be allowed sufficient time to consider participation in this research trial and have 
the opportunity to discuss this trial with their family, friends or legally authorized representative, 
or think about it prior to agreeing to participate. 
Informed consent forms will be IRB approved and subjects will be asked to read and review the 
consent form. Subjects must sign the informed consent form prior to starting any study 
procedures being done specifically for this trial. 
Once signed, a copy of the informed consent form will be given to the subject(s) for their 
records.  The subject(s) may withdraw consent at any time throughout the course of the trial.  
The rights and welfare of the subject(s) will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this study. 


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New information will be communicated by the site principal investigator to subjects who consent 
to participate in this trial in accordance with IRB requirements.  The informed consent document 
will be updated, and subjects will be re-consented per IRB requirements, if necessary.  Subjects 
will be given a copy of all informed consent forms that they sign. 
 
Consent for Future Use of Stored Specimens and Data 
At enrollment, subjects will be asked for consent to collect a venous blood sample (6 mL) for 
plasma at the presumed Cmax (6 hours post dose) in addition to PK blood samples to be retained 
for possible use in future research studies.  Permission to collect and store these samples will be 
completely voluntary; subjects who are otherwise eligible to participate in the study but do not 
consent to collection of future use specimens will not be excluded from the study. These clinical 
samples will be shipped to and stored up to two (2) years from the end of the study at the Fisher 
Biorepository (DMID CMS) and may be shared with investigators at the participating site and 
with other investigators at other institutions.  
Residual clinical samples with consent for future use will be available upon the completion of 
the study; however, future use clinical samples may be requested from DMID and shipped from 
the DMID CMS at any time. Residual clinical samples without consent for future use should be 
destroyed upon the completion of the study. 
The samples will not be sold or used directly for production of any commercial product.  No 
human genetic tests will be performed on the samples.  Each sample will be encoded (labeled) 
only with a barcode and a unique tracking number to protect subject confidentiality. The 
recipients of specimens will be informed that these specimens have a NIH certificate of 
confidentiality. 
There are no benefits to subjects in the collection, storage and subsequent use of their specimens 
for future research.  Reports about future research done with subjects’ samples will NOT be kept 
in their health records. 
Subjects may be given the option to decide if they want their samples to be used for future 
research or have their samples destroyed at the end of this trial.  The subject’s decision can be 
changed at any time by notifying the study doctors or nurses in writing.  However, if the subject 
originally consents to future use and subsequently changes his/her decision, any data from a 
previously collected sample may still be used for this research. 
Subjects may be given the option to decide if they want their residual specimens to be used for 
future research or have these specimens destroyed at the end of this trial. The subject’s decision 
can be changed at any time by notifying the study doctors or nurses in writing. However, if the 


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subject originally consents to the future use of residual specimens and subsequently changes 
his/her decision, any data from a previously collected specimen may still be used for future 
research. 
 
Exclusion of Women, Minorities, and Children (Special Populations) 
Children under age 18 years will be excluded from participation because insufficient data are 
available in adults to judge potential risk in children, and as a Phase 1 trial in healthy individuals, 
there is no known benefit. For these same reasons, this trial will not include other special classes 
of subjects, such as fetuses, neonates, prisoners, institutionalized individuals, or others who may 
be considered vulnerable populations. 
Neither women nor minorities will be excluded from participation in this study. Women of child 
bearing potential may be included as per the inclusion criteria (Section 5.1). Subjects will be 
recruited without regard to gender or race. It is expected that race will reflect that within the 
community.  
 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
the Sponsor and their agents. This confidentiality includes documentation, investigation data, 
subject’s clinical information, and all other information generated during participation in the 
study. No information concerning the study, or the data generated from the study will be released 
to any unauthorized third party without prior written approval of the DMID and the subject. 
Subject confidentiality will be maintained when study results are published or discussed in 
conferences.  The study monitors or other authorized representatives of the sponsor or 
governmental regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the subjects in this study. The clinical study site will permit 
access to such records. 
All records will be kept locked and all computer entry and networking programs will be carried 
out with coded numbers only and with password protected systems. All non-clinical specimens, 
evaluation forms, reports, and other records that leave the site will be identified only by a coded 
number. 
To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 


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other proceedings.  The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
 
Certificate of Confidentiality 
To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings.  The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the FDA). 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing 
information about themselves or their involvement in this research.  If any person or agency 
obtains a written consent to receive research information, then the researchers may not use the 
Certificate to withhold that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
subject’s consent, information that would identify the subject as a participant in the research 
project regarding matters that must be legally reported including: child and elder abuse, sexual 
abuse, or wanting to harm themselves or others.   
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains, or for the purposes of other research that is in compliance with applicable Federal 
regulations governing the protection of human subjects in research.  
 
Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for the research tests, procedures, and study product while taking part 
in this trial.  Procedures and treatment for clinical care may be billed to the subject, subject’s 
insurance or third party.   
Subjects are compensated for their participation in this trial.  Compensation will be in 
accordance with the local IRB’s policies and procedures, and subject to IRB approval. 
If it is determined by the site principal investigator that an injury occurred to a subject as a direct 
result of the tests or treatments that are done for this trial, then referrals to appropriate health care 


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facilities will be provided to the subject.  Study personnel will try to reduce, control, and treat 
any complications from this trial.  Immediate medical treatment may be provided by the 
participating site.  No financial compensation will be provided to the subject by the NIAID, NIH 
or by the participating site to the subject for any injury suffered due to participation in this trial. 
 


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STATISTICAL CONSIDERATIONS 
A formal Statistical Analysis Plan (SAP) will be created prior to final data lock. This document 
will provide a more technical and detailed description of the proposed data analysis methods and 
procedures. Any deviation from the analyses outlined in the protocol will be described in the SAP. 
For continuous variables, data will be summarized using descriptive statistics (such as sample 
size, mean, median, standard deviation, minimum, and maximum). For discrete variables, data 
will be summarized using frequencies and percentages.  
 Study Hypotheses 
The objectives of the study are to obtain safety and pharmacokinetic data for VT-1598. There are 
no formal hypotheses being tested in this Phase 1 trial study. 
 Sample Size Considerations 
As this study is the first assessment of VT-1598 in humans and is primarily aimed at safety and 
PK evaluation, power calculations have not been performed. The sample size of 8 subjects (6 
subjects receiving VT-1598 and 2 subjects receiving placebo) per cohort is based on clinical 
experience and judgment and should provide adequate clinical information to meet the objectives 
of the study.  The comparisons of fed to fasted PK are exploratory rather than formal analyses of 
fed bioequivalence and fed and fasted profiles from 6 subjects are sufficient for the intended 
purpose. 
 Treatment Assignment Procedures 
 Randomization Procedures 
Each subject who completes the study Screening assessments, meets all eligibility criteria, and is 
accepted for the study will be assigned a unique sequential identification number and, with the 
exception of replacement subjects, will receive the corresponding treatment according to the 
randomization schedule. Replacement subjects will receive the same treatment assignment as the 
subject being replaced. Subjects who are not randomized within 28 days of their Screening visit 
will be considered out-of-window and not eligible for randomization. These subjects will be 
eligible to re-screen provided they previously met all other eligibility criteria. 
The randomization schedule will be generated centrally through the AdvantageEDCSM 
(Electronic Data Capture System, Emmes) by the unblinded study biostatistician, and a list will 


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be transferred to the unblinded study pharmacist prior to start of the study for the purpose of an 
emergency back-up. For Cohort 1 through Cohort 5, within each cohort 8 subjects will be 
randomized in a 3:1 ratio to active treatment and placebo.  Cohort 6 will not use randomization. 
For Cohort 1 through Cohort 5, the first two subjects will be randomized in a 1:1 fashion to 
active drug and placebo to ensure that one of the first two subjects receives active treatment and 
the other receives placebo for sentinel dosing placebo.  The product assignment of the remaining 
six subjects in each cohort will be randomly assigned 5:1 active drug to placebo to ensure the 3:1 
ratio for the entire dosing cohort.  Enrollment will occur at one site. An appropriate amount of 
back-up subjects will be brought in per cohort in the event of subject withdrawal prior to dosing. 
After completing the final study visit (Day 21) and at least 60 days after dosing, Cohort 3 
subjects will have enrollment “rollover” to Cohort 6.  Cohort 3 subjects continuing as Cohort 6 
subjects will not be randomized but will receive placebo if he or she received placebo as part of 
Cohort 3 and will otherwise receive drug.  Cohort 3 subjects that do not continue to Cohort 6 will 
be replaced, and the replacement subjects will receive the same type of treatment (placebo vs. 
drug) that the subject being replaced received as part of Cohort 3. Cohort 3 subjects that are no 
longer eligible for the trial after the washout period will not be continued to Cohort 6 but will be 
replaced.  Cohort 6 “rollover” or replacement enrollment may occur before or after planned SMC 
meeting to be held once Cohort 4 has completed follow-up. 
Following review of all eligibility criteria, subjects will be registered and randomized using 
AdvantageEDCSM.  Randomization will occur following admittance to the unit and confirmation 
of eligibility is confirmed.  
Per ICH guideline E6: Good Clinical Practice (GCP), screening records will be kept at the 
participating site to document the reason why an individual was screened, but failed trial entry 
criteria.  The reasons why individuals failed screening will be recorded in the SDCC 
AdvantageEDCSM. 
Enrollment of subjects will be done online using the enrollment module of AdvantageEDCSM.  
The randomization code will be prepared by statisticians at the SDCC and included in the 
enrollment module for this trial.  AdvantageEDCSM will assign each subject to a treatment arm 
after the demographic and eligibility data have been entered into the system.  A designated 
individual at the participating site will be provided with a code list for emergency unblinding 
purposes by the unblinded study biostatistician, which will be kept in a secure place. 
Instructions for use of the enrollment module are included in the AdvantageEDCSM User’s 
Guide.  Manual back-up procedures and instructions are provided for use in the event that a 
participating site temporarily loses access to the Internet or the online enrollment system is 
unavailable. 


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 Masking Procedures 
Blinding 
The Study Pharmacist at the site will be unblinded as to treatment assignment. Study subjects, 
the PI and study site personnel other than the Study Pharmacist and verifier, the bioanalytical 
laboratory staff, and Fisher repository personnel will remain blinded to all randomization 
assignments throughout the study. The DMID medical monitor and NIAID personnel, NQP 1598 
Ltd., and ICON GPHS (CRO) personnel will remain blinded to all subject randomization 
assignments. 
All laboratory personnel performing experimental assays as part of this study will be masked to 
treatment group, subject ID, and study visit for all study specimens. The SDCC will generate 
sample picklists for each laboratory to determine which specimens will be tested. At the 
discretion of DMID, unmasking of laboratories may occur after all data have been locked, 
analyzed and interpreted and the final CSR has been completed.  
The randomization schedule will be provided to the unblinded study personnel (the Study 
Pharmacist and a verifier) at the site. The Pharmacist will perform dose preparation; the 
unblinded verifier is a member of the pharmacy team who will not participate in dose 
preparation. Unblinded personnel at the site will not be involved in study-related assessments or 
have subject contact for data collection following study drug administration. 
Selected individuals not involved in the conduct of the study, including members of the SMC, 
may have access to unblinded data as needed for safety review or other data review. The site 
pharmacist will remain unblinded during the course of the study. 
Emergency Unblinding 
Emergency unblinding of treatment assignment for a subject may be necessary due to a medical 
emergency, or any other significant medical event, should knowledge of the subject’s treatment 
assignment impact the subject’s care. Should an SAE or other circumstance require the blind to 
be broken to ensure a subject’s safety, the PI should immediately notify the DMID Medical 
Monitor if possible (within 24 hours) to discuss the case and reason for unblinding (a written 
narrative must follow within 48 hours of the event). 
Procedures for emergency unblinding are detailed in the MOP for this study.   


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 Planned Interim Analyses 
Safety data will be reviewed by the SMC by treatment received in a closed session in the planned 
safety data review meeting between Cohort 4 and Cohort 5 and may also be reviewed by SMC in 
the closed session of ad hoc meetings.   
There will be an interim analysis of PK data after completion of Cohort 3 which will be made 
available to all investigators, SDCC staff, NQP 1598 Ltd., and DMID staff involved in the study.  
The interim PK report will show PK data in aggregate only and will not include any information 
that could be potentially unblinding.  Enrollment will not stop for the PK interim analysis.  If PK 
is substantially different than expected, the protocol may be amended to change the timing of PK 
samples. 
 Final Analysis Plan 
The safety analysis population will include all subjects that received any amount of study 
product and will be analyzed by treatment received.  Placebo subjects may be pooled across 
multiple cohorts for analysis. The PK analysis population will include all subjects with at least 
one measurable PK concentration. 
    Adverse and Serious Adverse Events 
AEs will be coded with MedDRA (Version 22.1 or later) and summarized descriptively for each 
regimen by system organ class, HLGT, and preferred term. The AE profile will be characterized 
by severity and relationship to the study drug. SAEs will be identified.  
    Clinical Safety Labs, Vital Signs, and Electrocardiograms 
Baseline for clinical safety labs, vital signs, and ECGs will be defined as the last result obtained 
before the dose of study product.  Clinical safety labs, vital signs, and ECGs results and changes 
from baseline will be summarized by treatment arm and visit.  Clinical safety labs and vital signs 
will be graded (Appendix B) and summarized by severity, treatment arm, and visit. If triplicate 
ECG measurements were performed at the same visit, then baseline is the mean value of the 
measurements for the visit closest to, but before, administration of study drug. Similarly, for 
analyses of change from baseline, mean values will be used in the case of replicate 
measurements at a single visit post-baseline. 
Treatment-emergent abnormal laboratory test results will be identified. Treatment-emergent 
abnormal laboratory tests are tests for which the result was not graded as mild or worse at 
baseline but graded as mild or worse after dosing.  Laboratory tests graded as mild at baseline, 


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but moderate or worse any time after dosing will also be regarded as treatment-emergent 
abnormal laboratory test results. 
ECG measurements will include heart rate, RR interval, QT interval, QTcF interval, PR interval, 
and QRS duration. Baseline for ECG measurements is defined per protocol as the value pre-
dosing on Day 1. Change from baseline will be summarized descriptively by regimen at each 
scheduled evaluation. QTc results will be summarized categorically according to the ICH 
Guideline E14 “Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic Drugs” (October 2005). 
• 
QTcF >450 ms; 
• 
QTcF >450 ms, males only; 
• 
QTcF >470 ms, females only; 
• 
QTcF >480 ms;  
• 
QTcF >500 ms; 
• 
QTcF increases from baseline by at least 30 ms but less than 60 ms; 
• 
QTcF increases from baseline by at least 60 ms. 
 Pharmacokinetic Analysis Plan 
Plasma and urine samples from all subjects who received at least one dose of VT-1598 will be 
analyzed for the concentration of VT-1598 and VT-11134 by validated LC-MS/MS methods. 
Plasma concentration-time profiles and plots of amount excreted (Ae(t1-t2)) per urine collection 
period will be constructed for each subject and each dosing cohort.  
The following PK parameters will be estimated, by noncompartmental analysis methods using 
version 7.0 or higher of Phoenix WinNonlin®, for VT-1598 and VT-11134 plasma and urine 
concentration, as appropriate. 
Cmax 
maximum measured plasma concentration 
Tmax 
time to reach maximum measured plasma concentration 
AUClast 
area under the plasma concentration versus time curve from time 0 to 
the time of the last quantifiable concentration 


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AUCinf 
area under the plasma concentration versus time curve from time 0 and 
extrapolated to infinity 
%AUCex 
percentage of AUCinf obtained by extrapolation 
t1/2 
terminal phase half-life 
λz 
apparent first-order terminal elimination rate constant 
Vd/F 
apparent volume of distribution 
CL/F 
apparent oral clearance 
Aelast 
cumulative amount excreted into the urine from time 0 to the time of the 
last quantifiable concentration 
Ae%Dose 
cumulative amount excreted into the urine 
CLR 
renal clearance of drug 
Additional PK parameters may be estimated as appropriate. Dose proportionality for each PK 
exposure parameter (Cmax, AUClast, AUCinf) will be assessed statistically and graphically.  
The more detailed PK analysis will be available in the SAP for this study.   


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SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
The participating site will maintain appropriate medical and research records in compliance with 
ICH E6, Section 4.9 and regulatory and institutional requirements for the protection of 
confidentiality of subjects. The site will permit authorized representatives of the DMID, its 
designees, and appropriate regulatory agencies to examine (and when required by applicable law, 
to copy) clinical records for the purposes of quality assurance reviews, audits, and evaluation of 
the study safety and progress. These representatives will be permitted access to all source data 
and source documents, which include, but are not limited to, hospital records, clinical and office 
charts, laboratory notes, memoranda, subjects’ memory aid or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, copies or transcriptions certified 
after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, x-rays, and subject files and records kept at the pharmacy, at the laboratories, 
and medico-technical departments involved in the clinical trial.  
 Compliance with Standards of Medical Research/ Deviations 
This protocol will be conducted in accordance with the applicable ICH guidelines and GCP. Any 
instance of noncompliance with the protocol will result in a documented deviation. If a change is 
deemed necessary in order to protect the safety, rights or welfare of a subject, the Sponsor and 
IRB should be notified as soon as possible and preferably prior to introducing the deviation.  
 
 


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QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted Program Quality Management Plan (cQMP), the 
participating site and its subcontractors are responsible for conducting routine quality assurance 
(QA) and quality control (QC) activities to internally monitor study progress and protocol 
compliance.  The site principal investigator will provide direct access to all study-related sites, 
source data/data collection forms, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by local and regulatory authorities.  The site principal investigator will 
ensure all study personnel are appropriately trained and applicable documentations are 
maintained on site. 
The SDCC will implement quality control procedures beginning with the data entry system and 
generate data quality control checks that will be run on the database.  Any missing data or data 
anomalies will be communicated to the participating site(s) for clarification and resolution. 
DMID-designated clinical monitors will verify that the clinical trial is conducted, and data are 
generated, documented (recorded), and reported in compliance with the protocol, ICH/GCP 
guidelines, and the applicable regulatory requirements. Clinical monitoring reports will be 
submitted to DMID. 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory agencies 
may conduct a regulatory inspection at any time during or after the completion of the study. In 
the event of an assessment, audit or inspection, the Investigator (and institution) must agree to 
grant the advisor(s), auditor(s), and inspector(s) direct access to all relevant documents and to 
allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues, and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
 


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DATA HANDLING AND RECORD KEEPING 
 Data Management Responsibilities 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of 
the data reported.  All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.  Black or blue permanent ink is required to ensure clarity of 
reproduced copies.  When making changes or corrections, cross out the original entry with a 
single line, and initial and date the change.  DO NOT ERASE, OVERWRITE, OR USE 
CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
Data reported in the eCRF derived from source data collection forms should be consistent or the 
discrepancies should be explained. 
The sponsor and/or its designee will provide guidance to the site principal investigators and other 
study personnel on making corrections to the data collection forms and eCRF. 
Training will be provided for the Electronic Data Capture (EDC) system. All personnel using the 
EDC system must have the appropriate education, training, and experience, or any combination 
thereof. The Investigator will be provided with standard operating procedures (SOPs) (contained 
in the MOP or a vendor-specific SOP) on the use of the EDC system. Documentation for employee 
education, training, and previous experience that pertains to the EDC system must be present in 
the Investigator files. 
If electronic data systems other than those provided and maintained by the Sponsor are used for 
documentation and data capture, the Investigator must ensure that the systems are validated and 
ensure regular data back-up. 
The eCRF will be signed by the Investigator or a Sub-Investigator listed on the FDA 1572 form. 
It is the responsibility of the Investigator to ensure the eCRFs are completed and submitted to the 
Sponsor (or designee) in an accurate and timely manner. The processing of eCRFs will include an 
audit trail (to include changes made, reason for change, date of change, and person making 
change). At the completion of the study, the Sponsor will be provided with a final copy of each 
eCRF. 
Management of clinical data will be performed in accordance with applicable Sponsor standards 
and data cleaning procedures to ensure the integrity of the data (e.g., removing errors and 
inconsistencies in the data). Adverse events and concomitant medications will be coded using the 
MedDRA® and World Health Organization Drug Dictionaries (WHO DD) respectively.  Medical 
eCRFs will be retained by the Sponsor and copies will be sent to the Investigator to maintain as 
the Investigator copy. 


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 Data Coordinating Center/Biostatistician Responsibilities 
Any source documents and laboratory reports must be reviewed by the clinical team and data 
management staff, who will ensure their accuracy and completeness. AEs must be recorded on 
the appropriate data collection form, assessed for severity and relationship, and reviewed by the 
site principal investigator or appropriate sub-investigator.  AEs must be graded based on the 
FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials September 2007, as modified for this 
study and as appropriate for the administration of VT-1598 Appendix B VT-1598 Toxicity 
Grading Criteria for Normal Human Subjects. 
Electronic data capture is the responsibility of the clinical trial staff at the site under the 
supervision of the site PI. During the study, the PI must maintain complete and accurate 
documentation for the study. 
Data collection is the responsibility of the study personnel at the participating clinical study site 
under the supervision of the site principal investigator.  During the study, the site principal 
investigator must maintain complete and accurate documentation for the study. 
The data coordinating center for this study, Emmes, will be responsible for data management, 
quality review, analysis, and reporting of the study data. 
 Data Capture Methods 
Clinical data (including but not limited to AEs, physical assessments, clinical laboratory values 
and concomitant medications) will be entered into Advantage EDCSM, a 21 CFR Part 11-
compliant electronic data capture (EDC) system managed by Emmes. The EDC system access is 
password protected. Access is granted to specific individuals based on the roles identified for the 
study. The clinical study site enters the data into EDC from the data collection forms completed 
by the study personnel. Data are validated through a query resolution process, comprising both 
automated and manual queries. 
AE/SAEs, concomitant medications, medical history, physical assessments, and clinical 
laboratory values) and reactogenicity will be collected on data collection forms by study 
personnel then entered into eCRFs via a 21 CFR Part 11-compliant internet data entry system 
provided by the study data coordinating center.    


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 Types of Data 
Data for this study will include all data for safety and PK deemed necessary for the analysis per 
the protocol, demographic data, clinical laboratory values, concomitant medication, AE and 
medical history. 
Externally collected data are received and processed to present a complete dataset reconciled 
with data collected in the EDC. 
 
Study Records Retention 
Study documents will be retained for a minimum of 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. These documents will be retained for a 
longer period, however, if required by local regulations. No records will be destroyed without the 
written consent of the sponsor. It is the responsibility of the sponsor to inform the investigator 
when these documents no longer need to be retained. 


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CLINICAL MONITORING 
 Site Monitoring Plan 
Site monitoring is conducted to ensure that the human subjects’ protections, study and laboratory 
procedures, study intervention administration, and data collection processes are of high quality 
and meet sponsor, ICH/GCP guidelines and applicable regulations, and that this trial is 
conducted in accordance with the protocol, protocol-specific MOP and applicable sponsor 
standard operating procedures.  DMID, the sponsoring agency, or its designee will conduct site-
monitoring visits as detailed in the clinical monitoring plan. 
Site visits will be made at standard intervals as defined by DMID and may be made more 
frequently as directed by DMID.  Monitoring visits will include, but are not limited to, review of 
regulatory files, accountability records, eCRFs, informed consent forms, medical and laboratory 
reports, and protocol and GCP compliance.  Site monitors will have access to each participating 
site, study personnel, and all study documentation according to the DMID-approved site 
monitoring plan.  Study monitors will meet with site principal investigators to discuss any 
problems and actions to be taken and will document site visit findings and discussions. 


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PUBLICATION POLICY 
All investigators funded by the NIH must submit or have submitted for them to the National 
Library of Medicine’s PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) an electronic 
version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made 
publicly available no later than 12 months after the official date of publication.  The NIH Public 
Access Policy ensures the public has access to the published results of NIH funded research.  It 
requires investigators to submit final peer-reviewed journal manuscripts that arise from NIH 
funds to the digital archive PubMed Central upon acceptance for publication.  Further, the policy 
stipulates that these papers must be accessible to the public on PubMed Central no later than 12 
months after publication. 
Refer to: 
• 
NIH Public Access Policy, http://publicaccess.nih.gov/; 
• 
NIH Office of Extramural Research (OER) Grants and Funding, 
http://grants.nih.gov/grants/oer.htm. 
As of January 2018, all clinical trials supported by the NIH must be registered on 
ClinicalTrials.gov, no later than 21 days after the enrollment of the first subject. Results of all 
clinical trials supported by the NIH, generally, need to be submitted no later than 12 months 
following the primary completion date. A delay of up to 2 years is available for trials that meet 
certain criteria and have applied for certification of delayed posting. 
As part of the result posting a copy of this protocol (and its amendments) and a copy of the 
Statistical Analysis Plan will be posted on https://clinicaltrials.gov/. 
For this trial the responsible party is DMID, which will register the trial and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to: 
• 
Public Law 110-85, Section 801, Clinical Trial Databases 
• 
42CFR11 
• 
NIH NOT-OD-16-149 


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LITERATURE REFERENCES 
1. Yoshida Y. Cytochrome P450 of fungi: primary target for azole antifungal agents. Curr 
Top Med Mycol. 1988; 2: 388-418. 
2. Hitchcock CA. Cytochrome P-450-dependent 14 α-sterol demethylase of Candida 
albicans and its interaction with azole antifungals. Biochem Soc Trans. 1991; 19: 782- 
787. 
3. Bates DW and Yu DT. Clinical impact of drug-drug interactions with systemic azole 
antifungals. Drugs Today. 2003; 39: 801-813. 
4. Zarn JA, Bruschweiler BJ, Schlatter JR. Azole fungicides affect mammalian 
steroidogenesis by inhibiting sterol 14α-demethylase and aromatase. Env Health Pers. 
2003; 111: 255-261. 
5. Mathisen G, Shelub A, Truong J, and Wigen C. Coccidioidal meningitis: clinical 
presentation and management in the fluconazole era. Medicine. 2010; 89: 251-284. 
6. Brown J, Benedict K, Park BJ, and Thompson GR. Coccidioidomycosis: epidemiology. 
Clin Epidemiol. 2013; 5: 185-197. 
7. Welsh O, Vera-Cabrera L, Rendon A, Gonzalez G, Bonifaz A. Coccidioidomycosis. 
Clinics in Dermatology. 2012; 30: 573-591. 
8. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA, and 
Williams PL. Coccidioidomycosis. Clin Infect Dis. 2005; 41: 1217-23. 
9. Huang JY, Bristow B, Shafir S, and Sorvillo F. Coccidioidomycosis-associated deaths, 
United States, 1990-2008. Emerg Infect Dis. 2012; 18: 1723-8. 
10. Tsang CA, Anderson SM, Imholte SB, et al. Enhanced surveillance of 
coccidioidomycosis, Arizona, USA, 2007-2008. Emerg Infect Dis. 2010; 16: 1738-44. 
11. Sondermeyer G, Lee L, Gilliss D, Tabnak F, and Vugia D. Coccidioidomycosis 
associated hospitalizations, California, USA, 2000-2011. Emerg Infect Dis. 2013; 19: 
1590-7. 
12. Khan M and Brady S. Hospitalizations associated with coccidioidal meningitis in 
Arizona, 2008-2014. ID Week 2016, abstract 1607, New Orleans, LA. 


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13. Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America 
(IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin 
Infect Dis. 2016; 63(6): 112-46. 
14. Litvintseva AP, Marsden-Haug N, Hurst S, et al. Valley Fever: Finding new places for 
an old disease: Coccidioides immitis found in Washington state soil associated with 
recent human infection. Clinical Infectious Diseases: An Official Publication of the 
Infectious Diseases Society of America. 2015; 60(1): e1-e3. 
15. Centers for Disease Control and Prevention. Increase in Reported Coccidioidomycosis – 
US, 1998-2011. MMWR. 2013; 62: 217-21. 
16. Chang DC, Anderson S, Wannemuehler K, et al. Testing for coccidioidomycosis among 
patients with community-acquired pneumonia. Emerg Infect Dis. 2008; 14: 1053-9 
17. NIAID Emerging Infectious Diseases/Pathogens. National Institutes of Health, National 
Institute of Allergy & Infectious Diseases website. 
https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens. Updated 
October 26, 2016. Accessed November 3, 2016. 
18. Zonios DI and Bennett JE. Update on azole antifungals. Semin Respir Crit Care Med 
2008; 29:198-210. 


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APPENDICES 
 
 
 
 
 
 
 
 
 
 
 
 


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CONFIDENTIAL 
 
 
  VT-1598 SCHEDULE OF STUDY PROCEDURES AND 
EVALUATIONS   
Schedule of Study Procedures and Evaluations – Cohort 1 through Cohort 6* 
(X) – As indicated/appropriate  
 
 
 
Activity/ 
Day 
Screening Baseline 
Inpatient (Treatment) 
Period 
Follow-up Period 
Unscheduled 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 
Visit 6 
Day -28 
to-2 
Day -1 
Day 1 
Days 2 
& 3 
Day 4 
Day 7 
(±1 day) 
Day 14 
(±1 day) 
Day 21/ 
End-of- 
Studys 
 (±2 days) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
X 
 
 
 
 
 
 
 
Height, Weight, BMI 
X 
Xa 
 
 
 
 
 
 
 
Medical Historyb 
X 
X
c 
 
 
 
X
c 
X
c 
X
c 
 
Physical Examination 
Xd 
Xe 
Xe 
 
Xe 
 
 
Xe 
Xe 
Vital Signsf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
ECGg 
Xg 
 
Xg 
 
Xg 
 
 
Xg 
Xg 
Clinical Laboratory 
Testsh 
X 
X 
 
 
X 
X 
X 
X 
X 


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Activity/ 
Day 
Screening Baseline 
Inpatient (Treatment) 
Period 
Follow-up Period 
Unscheduled 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 
Visit 6 
Day -28 
to-2 
Day -1 
Day 1 
Days 2 
& 3 
Day 4 
Day 7 
(±1 day) 
Day 14 
(±1 day) 
Day 21/ 
End-of- 
Studys 
 (±2 days) 
Pregnancy Testi 
X 
X 
 
 
 
 
 
X 
 
FSHj 
X 
 
 
 
 
 
 
 
 
Drug Screenk 
X 
X 
 
 
 
 
 
 
 
Immunology Screenl 
X 
 
 
 
 
 
 
 
 
PK Blood Samplesm 
 
 
Xm 
Xm 
Xm 
Xm 
Xm 
Xm 
Xm 
PK Urine Samplesn 
 
 
Xn 
Xn 
Xn 
 
 
 
 
Future Use Specimen 
Collection 
 
 
X 
 
 
 
 
 
 
Prior/Concomitant 
Medications/Treatments 
X 
X 
Xo 
X 
X 
X 
X 
X 
X 
Review/confirm 
adherence to dietary 
restrictions/birth control 
methodsp 
X 
X 
 
 
X 
X 
X 
X 
 
Admit to CRU 
 
X 
 
 
 
 
 
 
 
Discharge from CRU 
 
 
 
 
X 
 
 
 
 
Receive study productq,r 
 
 
X 
 
 
 
 
 
 
Collect and Record AEs 
 
 
X 
X 
X 
X 
X 
X 
X 
 


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* Cohort 6 may enroll prior to the SMC meeting or prior to the start of Cohort 5 (but no less than 60 days after 
completion of Cohort 3).  
Abbreviations: AE: adverse event; BMI: body mass index; CBC: complete blood count; CRU: clinical research unit; 
ECG: electrocardiogram; EW: early withdrawal; FSH: follicle-stimulating hormone; HIV-1: Human 
Immunodeficiency Virus-1; HIV-2: Human Immunodeficiency Virus-2; HBsAg: Hepatitis B surface antigen; Anti-
HCV: anti-Hepatitis C virus; IMP: investigational medicinal product; PK: pharmacokinetics. 
Footnotes to Schedule of Assessments and Procedures: 
a Weight and BMI only. 
b Including alcohol and tobacco use history. 
c Update medical history as appropriate from previous visit. 
d Complete physical examination (general appearance; head, eyes, ears, nose, and throat; neck; chest and lungs; 
cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, and neurological system). 
e Targeted physical examination (general appearance, heart, lungs, skin and abdomen). On Day 4, targeted PE will 
be performed at 72 hours (±30 min).  
f Vital signs (heart rate, blood pressure, temperature, and respiratory rate) at Screening, Day -1, pre-dose on Day 1 
and approximately 1, 2, 4, 8, 24 (Day 2), 48 (Day 3), 72 (Day 4), 144 (Day 7 outpatient visit), 312 (Day 14 
outpatient visit) and 480 (Day 21 outpatient visit) hours after dosing. The pre-dose Day 1 vital signs measurements 
should be taken within 60 minutes of dosing.  Day 1 post-dose vital signs measurements should be taken ±10 
minutes of the nominal timepoint.  All other vital signs measurements during the inpatient stay should be taken 
within ± 30 minutes of the nominal time point. For outpatient visits, vital signs measurements should be taken 
within the visit window. All vital signs are taken after subject is at rest for at least 5 minutes. 
g ECGs will be performed at Screening; pre-dose taken within 60 minutes of dosing and post-dose, taken 4 hours) 
after dosing on Day 1;  at 72 hour (± 30 minutes) prior to discharge from the CRU on Day 4 (±15 min), and on Day 
21. All ECG readings are triplicate recordings, at least 1 minute apart within a 15-minute period and are taken after 
at least 5 minutes in the supine position. For the Day 21 outpatient visit, the ECG should be taken within the visit 
window. 
h Clinical laboratory tests to include: clinical chemistry panel (albumin, glucose, blood urea nitrogen or urea, 
potassium, calcium, sodium, chloride, total protein, creatinine, triglycerides, total cholesterol, low-density 
lipoprotein cholesterol, high-density lipoprotein cholesterol, total carbon dioxide, creatine phosphokinase, 
phosphorus, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct 
bilirubin, magnesium, gamma-glutamyl transferase (GGT) and serum cortisol), CBC (red blood cell count, total and 
differential white blood cell count, hemoglobin, hematocrit, and platelet count), coagulation parameters (activated 
partial thromboplastin time, prothrombin time, and international normalized ratio), and urinalysis (leukocyte 
esterase, blood, pH, and specific gravity [microscopic tests to be completed if dipstick urinalysis is abnormal]). 
Subjects must fast at least 8 hours before blood collection for the clinical chemistry panel.  Cortisol must be fasting 
and drawn before 10 a.m. 
i Serum pregnancy test for women of childbearing potential at Screening, Day -1 and Day 21 (Final Study Visit). 


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j Follicle-stimulating hormone on all post-menopausal women at Screening. 
k Urine drug test at Screening and on Day -1 to include cotinine, opiates, cocaine, cannabinoids, phencyclidine, 
benzodiazepines, barbiturates, amphetamines, and cotinine. Alcohol screen is performed by urine test. 
l Immunology screen to include tests for the detection of antibodies to HIV-1 and HIV-2, HBsAg, and antibodies to 
HCV. 
m PK blood samples will be collected on the following schedule following study product administration on Day 1: 
pre-dose, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72, 144 (Day 7 outpatient visit), 312 (Day 14 
outpatient visit) and 480 (Day 21 outpatient visit) hours post-dose. The pre-dose Day 1 PK blood sample should be 
taken within 60 minutes of before dosing for the fasted cohorts and within 30 minutes of the start of the pre-dose 
meal for the fed cohort; the Day 1 0.5-hour post dose blood sample should be taken within  ± 5 minutes of the 
nominal timepoint.  Remaining post-dose Day 1 PK blood samples should be taken within ± 10 minutes of the 
nominal time point. An additional 6 mL blood for future use is collected at 6 hours (±10 minutes) post dose. Day 2, 
3 and 4 PK blood samples should be taken within ± 30 minutes of the nominal time point.  For outpatient visits, PK 
blood samples should be taken within the visit window. PK blood samples take precedence; however, vital signs and 
ECGs should be completed before the blood draw, when possible. 
n PK urine samples will be collected in the following intervals following study product administration on Day 1: --
6to 0 hours before dose, and 0-6, 6-12, 12-24, 24-36, 36-48, 48-60, and 60-72 hours post-dose. 
.o A review for concomitant medication will be performed before and after dosing on Day 1. 
p Screening:  review birth control methods, permitted/non-permitted medications, non-medications, dietary and 
activity restrictions; Day -1: confirm that subject adhered to dietary restrictions (no food/beverages containing 
alcohol for previous 72 hours or caffeine for the previous 24 hours; no grapefruit, grapefruit juice, or juices 
containing grapefruit, or Seville oranges for previous 7 days); Days 7 and 14 - confirm that subject adhered to post-
discharge dietary restrictions (no consumption of grapefruit, or juices containing grapefruit or Seville oranges, no 
alcohol consumption) until after the visit to the CRU on Day 14;  Review post-discharge instructions (including 
birth control methods, permitted/non-permitted medications, non-medications, dietary and activity restrictions) 
qCohorts 1-5 will receive study product when fasted and subjects will remain fasted for at least 4 hours post-dose; 
Cohort 6 is administered study product following a high-fat, high-calorie meal, which is consumed within 30 
minutes and dosing is administered at 30 minutes after start of meal. 
r For the nominal dose escalations, the study product will be administered in a fasting state and the subjects will 
remain fasted for 4 hours post- dose.  Cohort 6 will be dosed with 160 mg of study product after ingestion of a high-
fat, high-calorie meal 
sFor unscheduled visits, Safety assessments including updated history and the following onsite evaluations: AE, PE, 
and any other study procedures deemed necessary by the PI will be obtained. Early termination assessments will be 
the same as the Day 21 procedures 
 
 


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VT-1598 TOXICITY GRADING CRITERIA FOR 
NORMAL HUMAN SUBJECTS 
Adverse Events* 
Mild 
Moderate    
(Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
Laboratory Adverse Events* (Blood, Serum or Plasma) 
Sodium (hyponatremia) – 
mEq/L 
131-132 
129-130 
<129 
Sodium (hypernatremia) – 
mEq/L 
144-145 
146-147 
>147 
Potassium (hyperkalemia) – 
mEq/L 
5.2 – 5.4 
5.5 – 5.6 
>5.6 
Potassium (hypokalemia) – 
mEq/L 
3.2-3.4 
3.0 – 3.1 
<3.0 
Phosphorus – mg/dL (Hypo) 
2.3 – 2.4 
2.1 – 2.2 
≤2.0 
Phosphorus – mg/dL (Hyper) 
N/A 
N/A 
N/A 
Magnesium – mg/dL   
1.3-1.5 
1.1-1.2 
<1.1 
Gamma- Glutamyl Transferase 
(GGT) – Male – U/L 
N/A 
N/A 
N/A 
Gamma- Glutamyl Transferase 
(GGT) – female – U/L 
N/A 
N/A 
N/A 
Glucose (hypoglycemia) – 
mg/dL 
65 – 69 
55 – 64 
<55 
Glucose (hyperglycemia) – 
mg/dL Fasting 
106 – 125 
126 – 200 
>200 
Blood Urea Nitrogen – mg/dL 
21-26 
27 – 31 
> 31 
Creatinine (Male) – mg/dL 
1.3 – 2.0 
2.1-2.3 
>2.3 
Creatinine (Female) – mg/dL 
1.0 – 1.7 
1.8 – 2.0 
>2.0 
Calcium (hypocalcemia) – 
mg/dL 
8.0 – <LLN 
7.5 – 7.9 
<7.5 


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Adverse Events* 
Mild 
Moderate    
(Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
Calcium (hypercalcemia) – 
mg/dL 
10.4-10.8 
10.9-11.4 
>11.4 
Chloride – mEq/L 
N/A 
N/A 
N/A 
CPKt-U/L (Male) 
1.1 - ≤ 1.5 x ULN 
>1.5 - ≤ 3.0 x ULN 
>3.0 ULN or higher 
CPKt – U/L(Female) 
1.1 - ≤ 1.5 x ULN 
>1.5 - ≤ 3.0 x ULN 
>3.0 ULN or higher 
A.M. Cortisol (serum, drawn 
prior to 10 a.m.) –  ug/dL 
1-10% below LLN 
10-25 % below LLN 
 >25% below LLN 
with or without 
symptoms 
Albumin (hypoalbuminemia) – 
g/dL 
2.8 – 3.4 
2.5 – 2.7 
< 2.5 
AST – U/L  
1.1 - ≤ 2.5 x ULN 
>2.5 - ≤ 5.0 x ULN 
>5.0 x ULN or higher 
ALT – U/L 
1.1 - ≤ 2.5 x ULN  
>2.5 - ≤ 5.0 x ULN 
>5.00 x ULN or higher 
Total Bilirubin (serum) – 
mg/dL 
  1.1 - ≤ 1.25 x ULN 
>1.25 - ≤ 1.50 x ULN 
>1.50 x ULN or higher 
Direct Bilirubin – mg/dL 
  1.1 - ≤ 1.25 x ULN 
>1.25 - ≤ 1.50 x ULN 
>1.50 x ULN or higher 
Indirect Bilirubin – mg/dL 
  1.1 - ≤ 1.25 x ULN 
>1.25 - ≤ 1.50 x ULN 
>1.50 x ULN or higher 
Amylase –  U/L 
1.1 - ≤ 1.5 x ULN 
>1.5 - ≤ 2.0 x ULN 
>2.0 x ULN or higher 
Lipase – U/L 
1.1 - ≤ 1.5 x ULN 
>1.5 - ≤ 2.0 x ULN 
>2.0 x ULN or higher 
Hemoglobin (Male) – g/dL 
11.2 - 12.2 
10.0 – 11.1 
<10.0 
Hemoglobin (Female) – g/dL 
9.8 - 10.8 
8.5 - 9.7 
<8.5 
WBC Increase – cell/mm3 
10,001– 15,000 
15,001 – 20,000 
> 20,000 
WBC Increase – cell/mm3 
(African America Males) 
9,001 – 14, 000 
14,001 – 19, 000 
>19,000 
WBC Increase – cell/mm3 
(African American Females) 
11,001 – 15,000 
15,001 – 20,000 
>20,000 


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Adverse Events* 
Mild 
Moderate    
(Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
WBC Decrease – cell/mm3 
2,500– 3,999 
1,500 – 2,499 
< 1,500 
WBC Decrease – cell/mm3 
(African American Males) 
2,200 – 2,499 
1,200 – 2,199 
<1,200 
WBC Decrease – cell/mm3 
(African American Females) 
2,200 – 2,499 
1,500 – 2,199 
<1,500 
Neutrophils Decrease –
cell/mm3 
1,300 – <1,699 
1,000 – 1,299 
< 1,000 
Neutrophils Decrease – 
cell/mm3 (African American 
Males) 
1,000 – 1,299 
800 - 999 
<800 
Neutrophils Decrease – 
cell/mm3 (African American 
Females) 
1,100 – 1,299 
1,000 – 1,099 
<1,000 
Platelets Decreased - cell/mm3 
120,000 – <150,000 
100,000 – 119,999 
<100,000 
PT (prothrombin time) – 
seconds 
 11.6 – 12.6  
 
12.7 – 13.7 
 >13.7 
PT INR (Prothrombin INR) 
1.2-1.4 
1.5-1.9 
2.0 or higher 
PTT (partial thromboplastin 
time) –seconds 
 30.1 – 36.8  
36.9 – 43.6  
>43.6 
Total Protein – g/dL 
5.5 - 5.9 
5.0 - 5.4 
<5.0 
Alkaline phosphatase – IU/L 
(Male) 
1.1 - ≤ 2.0 x ULN 
>2.0 - ≤ 3.0 x ULN 
>3.0 x ULN or higher 
Alkaline phosphatase – IU/L 
(Female) 
1.1 - ≤ 2.0 x ULN 
>2.0 - ≤ 3.0 x ULN 
>3.0 x ULN or higher 
Hematocrit (Male) - % 
33.0 -36.1 
29.8 - 32.9 
< 29.8 
Hematocrit (Female) - %  
29.5 - 32.6 
26.0 – 29.4 
< 26.0  
RBC (Male) – x 106/uL   
3.9 - 4.1 
3.4 - 3.8 
< 3.4 


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Adverse Events* 
Mild 
Moderate    
(Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
RBC (Female) – x 106/uL   
3.5 - 3.7 
3.0 - 3.4 
< 3.0 
Lymphocytes - cell/mm3 
decrease 
600- 799 
500 – 599 
< 500 
Monocytes – cell/mm3     
increase 
1001-2000 
2001-3000 
>3000 
Eosinophils - cell/mm3     
increase 
871 - 950 
951 - 1700 
>1700 
Basophils - cell/mm3       
increase 
101 - 300 
301 - 800 
> 800 
High Density Lipoproteins 
(HDL) Male – mg/dL 
N/A 
N/A 
N/A 
High Density Lipoproteins 
(HDL) Female – mg/dL 
N/A 
N/A 
N/A 
Total Carbon Dioxide – mEq/L 
N/A 
N/A 
N/A 
Total Cholesterol – mg/dL 
N/A 
N/A 
N/A 
Low Density Lipoprotein 
Cholesterol, Direct – mg/dL 
N/A 
N/A 
N/A 
Triglycerides – mg/dL 
N/A 
N/A 
N/A 
Laboratory Adverse Events* (Urine) 
Protein 
1+ 
2+ 
>2+ 
Glucose 
1+ 
2+ 
>2+ 
Blood (microscopic) - red 
blood cells per high power 
field (rbc/hpf)** 
3-10** 
11-50** 
>50 and/or gross 
blood** 
*Abnormal laboratory values, performed as part of hematology, chemistry panel, or urinalysis but not listed in 
Appendix B,  VT-1598 TOXICITY GRADING CRITERIA FOR NORMAL HUMAN SUBJECTS, will be 
evaluated by the study clinicians, recorded in the source document and, if clinically significant, considered AEs 
and graded according to the criterion described in Section 8.1. 


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Adverse Events* 
Mild 
Moderate    
(Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
** Hematuria during active menses is considered not clinically significant. 
 
Vital Sign Adverse Events 
Mild  
(Grade 1) 
Moderate 
 (Grade 2) 
Severe (Grade 3) 
Fever 
(°C) 
(°F) 
 
38.0 – 38.4 
100.4 – 101.1 
 
38.5 – 38.9 
101.2 – 102.0 
 
39.0 – 40 
102.1 – 104 
ECG – QTcF (ms) 
> 30 but ≤60 above 
baseline  
>60 above baseline to 
≤500  
>500  
Tachycardia – (beats per 
minute) 
101 – 115 
116 – 130 
>130 
Bradycardia – (beats per 
minute) 
50-54 if baseline >60 
45-49 if baseline >60 
<45 if baseline >60 
45-50 if baseline ≤ 60 
40-44 if baseline ≤ 60 
<40 if baseline ≤ 60 
Hypertension (systolic) – 
mmHg 
141 – 150 
151 – 155 
>155 
Hypertension (diastolic) 
– mmHg 
91 – 95 
96 – 100 
>100 
Hypotension (systolic)  
– mmHg 
85 – 89 
80 – 84 
<80 
Respiratory Rate – breaths 
per minute 
17-20 
21-25 
>25 
Nausea/vomiting 
No to mild interference 
with activity or 1 to 2 
episodes/24 hours 
Moderate interference 
with activity or >2 
episodes/24 hours 
Prevents daily activity, 
requires outpatient IV 
hydration 
Diarrhea 
2 - 4 loose stools or 
5-6 stools or 400 – 800 
7 or more watery stools or 
>800gms/24 hours or 


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Vital Sign Adverse Events 
Mild  
(Grade 1) 
Moderate 
 (Grade 2) 
Severe (Grade 3) 
< 400 gm/24 hours 
gm/24 hours 
requires outpatient IV 
hydration 
Headache 
No interference with 
activity 
Repeated use of non-
narcotic pain 
reliever > 24 hours or 
some interference with 
activity 
Significant; any use of 
narcotic pain reliever or 
prevents daily activity 
Fatigue 
No interference with 
activity 
Some interference with 
activity 
Significant; prevents daily 
activity 
Adverse Events – Other 
Illness or clinical AE (as 
defined according to 
applicable regulations 
No interference with 
activity 
Some interference with 
activity, not requiring 
medical intervention 
Prevents daily activity and 
requires medical 
intervention 
 
 

SAP_001.pdf: 
CLINICAL RESEARCH IN INFECTIOUS DISEASES 
STATISTICAL ANALYSIS PLAN 
for 
DMID Protocol: 17-0087 
Study Title: 
A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo 
Controlled, Single Dose-Escalation Study to Evaluate the Safety 
and Pharmacokinetics of Single Oral Doses of VT-1598 in Healthy 
Adult Subjects 
NCT04208321 
Version 1.0 
DATE: 05JAN2022 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- ii -
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 17-0087 
Development Phase: 
Phase 1 
Products: 
VT-1598 and Placebo 
Form/Route: 
Tablet/Oral 
Indication Studied: 
Coccidioidomycosis 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
29SEP2020 
Clinical Trial Completion Date: 
TBD 
Date of the Analysis Plan: 
05JAN2022 
Version Number: 
1.0 
This study was performed in compliance with Good Clinical Practice. 
Information contained in this publication is the property of Division of Microbiology and Infectious Diseases and is confidential. This information 
may not be disclosed to third parties without written authorization from Division of Microbiology and Infectious Diseases. This report may not be 
reproduced, stored in a retrieval system or transmitted in any form or by any means - electronic, mechanical, recording or otherwise - without 
the prior authorization from Division of Microbiology and Infectious Diseases. This document must be returned to Division of Microbiology and 
Infectious Diseases upon request. 


Statistical Analysis Plan - DMID Protocol: 17-0087 
Version 1.0 
05JAN2022 
- iii -
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
TABLE OF CONTENTS 
STUDY TITLE ............................................................................................................................... II 
TABLE OF CONTENTS ...............................................................................................................III 
LIST OF ABBREVIATIONS ....................................................................................................... VI 
1.
PREFACE .....................................................................................................................1 
2.
INTRODUCTION ........................................................................................................2 
2.1. 
Purpose of the Analyses ................................................................................................2 
3.
STUDY OBJECTIVES AND ENDPOINTS ................................................................3 
3.1. 
Study Objectives ...........................................................................................................3 
3.2. 
Endpoints ......................................................................................................................3 
3.3. 
Study Definitions and Derived Variables .....................................................................3 
3.3.1. 
Cohort ...........................................................................................................................3 
3.3.2. 
Dose Group ...................................................................................................................4 
3.3.3. 
Timepoints for Safety and PK Endpoints .....................................................................5 
3.3.4. 
Baseline .........................................................................................................................5 
3.3.5. 
Study Day .....................................................................................................................5 
4.
INVESTIGATIONAL PLAN .......................................................................................6 
4.1. 
Overall Study Design and Plan .....................................................................................6 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ........................7 
4.3. 
Selection of Study Population ......................................................................................7 
4.4. 
Treatments ..................................................................................................................10 
4.4.1. 
Treatments Administered ............................................................................................10 
4.4.2. 
Identity of Investigational Product(s) .........................................................................10 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .....................10 
4.4.4. 
Selection of Doses in the Study ..................................................................................11 
4.4.5. 
Selection and Timing of Dose for Each Subject .........................................................11 
4.4.6. 
Blinding ......................................................................................................................11 
4.4.7. 
Prior and Concomitant Therapy ..................................................................................12 
4.4.8. 
Treatment Compliance ................................................................................................12 
4.5. 
Safety and Pharmacokinetic Variables .......................................................................12 
5.
SAMPLE SIZE CONSIDERATIONS .......................................................................15 
6.
GENERAL STATISTICAL CONSIDERATIONS ....................................................16 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
Table of Contents (continued) 
- iv -
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
6.1. 
General Principles .......................................................................................................16 
6.2. 
Timing of Analyses .....................................................................................................16 
6.3. 
Analysis Populations ..................................................................................................16 
6.3.1. 
Safety Population ........................................................................................................16 
6.3.2. 
PK Analysis Population ..............................................................................................17 
6.3.2.1. 
PK Analysis Subset.....................................................................................................17 
6.4. 
Covariates and Subgroups ..........................................................................................17 
6.5. 
Missing Data ...............................................................................................................17 
6.6. 
Interim Analyses and Data Monitoring ......................................................................17 
6.7. 
Multicenter Studies .....................................................................................................18 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................18 
7.
STUDY SUBJECTS ...................................................................................................19 
7.1. 
Disposition of Subjects ...............................................................................................19 
7.2. 
Protocol Deviations ....................................................................................................19 
8.
EFFICACY EVALUATION ......................................................................................20 
9.
SAFETY EVALUATION ..........................................................................................21 
9.1. 
Demographic and Other Baseline Characteristics ......................................................21 
9.1.1. 
Prior and Concurrent Medical Conditions ..................................................................21 
9.1.2. 
Prior and Concomitant Medications ...........................................................................21 
9.2. 
Measurements of Treatment Compliance ...................................................................22 
9.3. 
Adverse Events ...........................................................................................................22 
9.3.1. 
Solicited Events and Symptoms .................................................................................22 
9.3.2. 
Unsolicited Adverse Events ........................................................................................22 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ....................23 
9.5. 
Pregnancies .................................................................................................................23 
9.6. 
Clinical Laboratory Evaluations .................................................................................23 
9.7. 
Vital Signs and Physical Evaluations .........................................................................25 
9.8. 
12-Lead Standard Electrocardiogram .........................................................................25 
9.9. 
Other Safety Measures ................................................................................................26 
10.
PHARMACOKINETICS ...........................................................................................27 
10.1. 
Graphical and Tabular Summaries of Pharmacokinetic Profiles ................................27 


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10.2. 
Noncompartmental Analysis ......................................................................................29 
10.3. 
Statistical Analysis ......................................................................................................32 
10.3.1. 
Assessment of Dose Proportionality ...........................................................................32 
10.3.2. 
Analysis of Change in Tmax between Fasted and Fed Dose Groups ...........................33 
10.3.3. 
Analysis of Exposure Parameter Ratios between Fasted and Fed Dose 
Groups .........................................................................................................................33 
11.
IMMUNOGENICITY ................................................................................................35 
12.
OTHER ANALYSES .................................................................................................36 
13.
REPORTING CONVENTIONS ................................................................................37 
14.
TECHNICAL DETAILS ............................................................................................38 
15.
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR
PLANNED ANALYSES ............................................................................................39 
16.
REFERENCES ...........................................................................................................40 
17.
LISTING OF TABLES, FIGURES, AND LISTINGS ..............................................41 
APPENDICES ...............................................................................................................................42 
APPENDIX 1. TABLE MOCK-UPS..........................................................................................43 
APPENDIX 2. FIGURE MOCK-UPS ......................................................................................114 
APPENDIX 3. LISTINGS MOCK-UPS ...................................................................................167 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
Aelast 
Cumulative amount of drug or metabolite excreted into the urine from time 0 
to the time of the last quantifiable concentration 
Ae%Dose 
Percent of drug or metabolite excreted into urine 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Classification 
AUC 
Area under the concentration-time curve 
AUC0-last 
AUC to the last measurable concentration 
AUC0-inf 
AUC extrapolated to infinity 
%AUCex 
Percentage of AUC0-inf obtained by extrapolation 
BMI 
Body Mass Index 
BQL 
Below the Limit of Quantification 
CHEM 
Chemistry 
CI 
Confidence Interval 
CL/F 
Apparent Oral Clearance 
CLR 
Renal Clearance of Drug or Metabolite 
Cmax 
Maximum Concentration 
COAG 
Coagulation 
CRF 
Case Report Form 
CRU 
Clinical Research Unit 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
CV 
Coefficient of Variation 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 


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FIH 
First-In-Human 
FSH 
Follicle Stimulating Hormone 
GGT 
Gamma-Glutamyl Transferase 
GM 
Geometric Mean 
hCG 
Human Chorionic Gonadotropin 
HBsAg 
Hepatitis B Surface Antigen 
HCV 
Hepatitis C Virus 
HDL 
High Density Lipoproteins 
HEM 
Hematology 
HIV 
Human Immunodeficiency Virus 
HLGT 
High-Level Group Term 
ICH 
The International Council for Harmonization 
ICON BAL 
ICON Bioanalytical Laboratory 
ID 
Identification 
ISM 
Independent Safety Monitor 
IUD 
Intrauterine Devices 
LC-MS/MS 
Liquid Chromatography with Tandem Mass Spectrometry 
LDL 
Low Density Lipoprotein 
LLOQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
Max 
Maximum 
Min 
Minimum 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 
NCA 
Noncompartmental Analysis 
NCS 
Not Clinically Significant 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
ONR 
Out of Normal Range 
PI 
Principal Investigator 


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PK 
Pharmacokinetics 
PT 
Preferred Term 
PTT 
Partial Thromboplastin Time 
QNS 
Quantity not Sufficient 
RBC 
Red Blood Cells 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
t1/2 
Apparent terminal elimination half-life 
Tlast 
Time of the last measurable concentration 
Tmax 
Time to obtain maximum concentration 
UA 
Urinalysis 
Vd/F 
Apparent volume of distribution during terminal phase 
VS 
Vital Sign 
WBC 
White Blood Cell 
λz 
Apparent first-order terminal elimination rate constant 


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1.
PREFACE
The Statistical Analysis Plan (SAP) for “A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo 
Controlled, Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses 
of VT-1598 in Healthy Adult Subjects” (Division of Microbiology and Infectious Diseases (DMID) Protocol 
17-0087) describes and expands upon the statistical information presented in the protocol.
This document describes all planned analyses and provides reasons and justifications for these analyses. It 
also includes sample tables, listings, and figures planned for the final analyses. This SAP follows the 
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals 
for Human Use (ICH) Guidelines, as indicated in Topic E3 (Structure and Content of Clinical Study Reports 
(CSRs)) [1], and more generally is consistent with Topic E8 (General Considerations for Clinical Trials) [2], 
and Topic E9 (Statistical Principles for Clinical Trials) [3]. The structure and content of the SAP provides 
sufficient detail to meet the requirements identified by the Food and Drug Administration (FDA) and ICH, 
while all work planned and reported for this SAP will follow internationally accepted guidelines published by 
the American Statistical Association and the Royal Statistical Society of statistical practice. 
This document contains four sections: (1) a review of the study design, (2) general statistical considerations, 
(3) comprehensive statistical analysis methods for the safety and pharmacokinetic (PK) outcomes, and (4) a
list of proposed tables, figures, and listings. Within the table, figure, and listing mock-ups (Appendices1, 2,
and 3), references to CSR sections are included. Any deviation from this SAP will be described and justified
in the CSR. The reader of this SAP is encouraged to also review the study protocol for details on conduct of
the study and the operational aspects of clinical assessments.


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2.
INTRODUCTION
This is a Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled study to evaluate the 
safety and PK of single ascending doses (SAD) of VT-1598 administered in healthy adult subjects among 6 
cohorts (5 fasted cohorts, 1 fed cohort). Each cohort contains 8 subjects (N = 8), 6 subjects will be given an 
oral dose of VT-1598 and 2 subjects will receive placebo. 
2.1. 
Purpose of the Analyses 
This SAP describes safety and PK analyses of 40 mg, 80 mg, 160 mg, 320 mg, and 640 mg of VT-1598 given 
orally under a fasted state; and of 160 mg of VT-1598 given orally under a fed state (after administration of a 
high-fat, high calorie meal). PK analyses include assessment of VT-1598 and its primary metabolite, VT-
11134. 


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3.
STUDY OBJECTIVES AND ENDPOINTS
3.1. 
Study Objectives
Primary: 
•
To determine the safety of single-ascending oral doses of VT-1598 in healthy adult subjects in a fasted
state.
•
To determine the safety of a single oral dose of VT-1598 in healthy adult subjects in a fed state.
Secondary: 
•
To determine the PK profile in plasma and urine of VT-1598 and its primary metabolite, VT-11134, in
healthy adult subjects.
•
To determine the effect of a high-fat, high-calorie meal on the PK profile of VT-1598 and VT-11134
when a single oral dose of VT-1598 is given.
3.2. 
Endpoints 
Primary: 
•
Safety will be evaluated for single-ascending fasting oral doses of VT-1598. Safety will be assessed by
adverse events (AE) from start of dosing to Day 21, clinical laboratory tests at baseline and from Day
4 to Day 21, vital signs (VS) at baseline and from Day 1 to Day 21, and electrocardiogram (ECGs) at
baseline and on Day 1, Day 4, and Day 21;
•
Safety will be evaluated for single oral dose of VT-1598 administered after being fed a high-fat, high-
calorie meal. Safety will be assessed by adverse effects from start of dosing to Day 21, clinical
laboratory tests at baseline and from Day 4 to Day 21, VS at baseline and from Day 1 to Day 21, and
ECGs at baseline and on Day 1, Day 4, and Day 21.
Secondary: 
•
PK profiles of VT-1598 and its primary metabolite, VT-11134, will be assessed by measurement of
VT-1598 and VT-11134 levels in both plasma and urine after VT-1598 administration in each cohort,
when fasting. Plasma for PK analysis will be collected at planned timepoints up to 480 hours post dose
and urine for PK analysis will be collected in planned intervals up to 72 hours post dose.
•
PK profiles of VT-1598 and its primary metabolite, VT-1134 will be assessed by measurement of VT-
1598 and VT-11134 levels in both plasma and urine after administration of VT-1598 following
consumption of a high-fat, high-calorie meal. Plasma for PK analysis will be collected at planned
timepoints up to 480 hours post dose and urine for PK analysis will be collected in planned intervals
up to 72 hours post dose.
3.3. 
Study Definitions and Derived Variables 
3.3.1. 
Cohort 
Cohort in the SAP will be defined to match identically with cohort as defined in the protocol (Table 1). 


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Fasted cohorts: 
•
Cohort 1: Single 40 mg tablet of VT-1598 (6 subjects) or matching placebo (2 subjects)
•
Cohort 2: Two 40 mg tablets (80 mg total) of VT-1598 (6 subjects) or matching placebo (2 subjects)
•
Cohort 3: Four 40 mg tablets (160 mg total) of VT-1598 (6 subjects) or matching placebo (2 subjects)
•
Cohort 4: Four 80 mg tablets (320 mg total) of VT-1598 (6 subjects) or matching placebo (2 subjects)
•
Cohort 5: Eight 80 mg tablets (640 mg total) of VT-1598 (6 subjects) or matching placebo (2 subjects)
Fed cohort: 
•
Cohort 6: Four 40 mg tablets (160 mg total) of VT-1598 or matching placebo, following a high-fat,
high-calorie meal. Cohort 6 will be comprised of the same subjects as Cohort 3 who will be assigned
the same treatment arm as randomized in Cohort 3. Subjects who complete Cohort 3 but withdraw or
become ineligible prior to dosing for Cohort 6 will be replaced. The Cohort 6 replacement subjects
will receive the same study product as assigned to the Cohort 3 subject they are replacing.
3.3.2. 
Dose Group 
Dose Group defines a grouping of subjects for statistical analysis, where subjects within a Dose Group receive 
the same study product and dose under the same fasting status. Two combined Dose Groups, the Any Dose 
and Placebo Dose Groups, will include all subjects who receive the same study product (VT-1598 or Placebo, 
respectively) regardless of the subject’s fasting status. Subjects who participate in both Cohort 3 and Cohort 6 
will be counted separately for each dosing period based on the study product received. Any summary tables 
including a column for ‘All Subjects’ will also count Cohort 3 and Cohort 6 subjects separately for each 
dosing period. For data from a subject to be analyzed as part of their Dose Group, the subject must also 
qualify for inclusion into the respective analysis population (Section 6.3). The Dose Groups in the order they 
will be presented are defined as follows:  
•
Any Dose: All subjects who received a complete or incomplete dose of VT-1598 regardless of fasting
status. Subjects who received VT-1598 in Cohort 3 and continued to Cohort 6 will be included in the
Any Dose Group separately for each dosing period.
•
40 mg Fasted: Cohort 1 subjects who received a complete dose of active drug under a fasted state.
•
80 mg Fasted: Cohort 2 subjects who received a complete dose of active drug under a fasted state.
•
160 mg Fasted: Cohort 3 subjects who received a complete dose of active drug under a fasted state.
•
160 mg Fed: Cohort 6 subjects who received a complete dose of active drug following a high-fat,
high-calorie meal.
•
320 mg Fasted: Cohort 4 subjects who received a complete dose of active drug under a fasted state.
•
640 mg Fasted: Cohort 5 subjects who received a complete dose of active drug under a fasted state.
•
Placebo: All subjects who received a complete or incomplete dose of placebo, regardless of fasting
status. Subjects who received placebo in Cohort 3 and continued to Cohort 6 will be included in the
Placebo group separately for each dosing period (unless replaced as detailed in Section 4.4.3).
Analyses by Dose Groups will be presented in the following order: Any Dose (when included), 40 mg Fasted, 
80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, and Placebo.  


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In the unlikely case that a subject is given the wrong dose, that subject may be analyzed based on actual dose 
received or with a different Dose Group than those described above. Reasoning for assigning the subject to a 
different Dose Group will be described in the CSR. The “Any Dose” group will be included in the analyses of 
safety endpoints only. 
3.3.3. 
Timepoints for Safety and PK Endpoints 
Table 7 shows the analysis timepoints in the order that will appear in tables and figures along with the safety 
and PK endpoints measured at each timepoint for all cohorts. Endpoints analyzed by timepoint include 
chemistry clinical laboratory results (CHEM), hematology clinical laboratory results (HEM), coagulation 
clinical laboratory results (COAG), and urinalysis laboratory results (UA); VS; ECG; and blood PK and urine 
PK samples. Serology, toxicology, and pregnancy testing at Screening will not be included in tables or figures 
but will be presented in listings.  
3.3.4. 
Baseline 
Baseline for clinical laboratory results and VS will be defined as the last result obtained before study product 
administration. If triplicate ECG measures were performed at the same visit, baseline ECG will be defined as 
the mean value of the last triplicate measurements before study product administration.  
Baseline height, weight, and body mass index (BMI) will be the measurements obtained at Screening. Age 
will be based on age at the time of enrollment. 
3.3.5. 
Study Day 
Study Day will primarily be used in listings to refer to the timing of assessments and events relative to study 
product administration. The day that the first dose of study product is received is considered Study Day 1 for 
all subjects. The day prior to the first dose is considered Study Day -1, there is no Study Day 0.  


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4.
INVESTIGATIONAL PLAN
4.1. 
Overall Study Design and Plan 
This is a Phase 1, randomized, double-blind, placebo-controlled, SAD study in healthy adult subjects. It is 
designed to evaluate the safety and PK of single oral doses of VT-1598. An overall schematic of study design 
is shown in Figure 1. A flowchart of subject disposition will be shown in Figure 2, and a table showing all 
planned study cohorts and dose levels can be found in Table 1. There will be 5 fasted cohorts: 40 mg 
VT-1598 or matching placebo, 80 mg VT-1598 or matching placebo, 160 mg VT-1598 or matching placebo, 
320 mg VT-1598 or matching placebo, 640 mg VT-1598 or matching placebo, and one fed cohort: 160 mg 
VT-1598 or matching placebo following a high-fat, high-calorie meal.  
A maximum of 40 subjects at a single site will be enrolled in the study to one of the fasted cohorts (Cohorts 1-
5). Within each fasted cohort, a total of 8 subjects will be randomized 3:1 to receive active drug (VT-1598) (6 
subjects) or placebo (2 subjects). For Cohort 1 through Cohort 5, the first 2 subjects will be randomized 1:1 to 
receive active drug or placebo to ensure that 1 of the first 2 subjects receives active drug and the other 
receives placebo for sentinel dosing. The study product assignment of the remaining 6 subjects in each of the 
fasted cohorts (Cohorts 1-5) will be randomly assigned 5:1 active drug to placebo to maintain the 3:1 ratio for 
the entire cohort. All sentinel subject safety data through Day 3 will be reviewed by the Principal Investigator 
(PI) prior to dosing the remaining 6 subjects in each fasted cohort.  
Subjects who complete Cohort 3 and do not early terminate from the study will have enrollment “rollover” to 
Cohort 6, the fed cohort, after a minimum of 60 days for a “wash-out” period. Cohort 3 subjects continuing to 
Cohort 6 will not be randomized but will receive the same study product and dose as they received in Cohort 
3 (160 mg VT-1598 or matching placebo) following a high-fat, high-calorie meal. Furthermore, there will be 
no sentinel subjects in Cohort 6. Cohort 3 subjects that are no longer eligible for the trial after the wash-out 
period will be replaced (Section 4.4.3). Subjects replacing individuals from Cohort 3 who did not continue on 
to Cohort 6 will not be randomized and will receive the same study product assignment as the Cohort 3 
subject they are replacing. 
A schedule of study procedures is detailed in Table 2. Screening, baseline, and follow-up procedures will 
follow the same process for all cohorts. Inpatient period (Study Days 1-4) procedures will differ between the 
fasted (Cohorts 1-5) and fed (Cohort 6) cohorts only by the high-fat, high-calorie meal and timing of inpatient 
pre-dose assessments. Baseline blood PK samples, targeted physical examination, and 12-lead ECG will be 
conducted within 60 minutes of dosing for the fasted cohorts (Cohorts 1-5). Baseline urine PK samples will be 
collected within 6 hours prior to dosing for the fasted cohorts (Cohorts 1-5). For Cohort 6, these procedures 
will be conducted within 30 minutes prior to the start of the meal. The high-fat, high-calorie meal will be 
entirely consumed within 30 minutes, and Cohort 6 subjects will be dosed within 30 minutes of the start of the 
meal. Post-dose inpatient period procedures will be the same for all cohorts. Safety assessments will include 
clinical laboratory tests including CHEM, HEM, COAG, and UA; VS; and a 12-lead standard ECG. AEs and 
serious adverse events (SAEs) will be assessed from the time of dosing to the end of the trial.   
A Safety Monitoring Committee (SMC) will be appointed to oversee the safe conduct of the trial. If criteria 
for halting the trial are met during the study, dosing and enrollment will be suspended, and an ad hoc SMC 
meeting will be convened to review all available safety data and to make recommendations about the dosing 
of all further subjects in the trial. A scheduled SMC meeting will be held after Cohort 4 for safety 
recommendations and confirmation of dosing before beginning Cohort 5. The SMC will also review safety 
data at an organizational meeting prior to the start of the study, at a scheduled meeting upon completion of 
dosing, final visit for all cohorts, and at the request of DMID.  


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There will be an interim analysis of PK data after completion of Cohort 3. The interim PK report will show 
PK data in aggregate and will not include any potentially unblinding information. Enrollment will not stop for 
the interim PK analysis. If PK is substantially different than expected, the protocol may be amended to change 
the timing of PK samples.  
4.2. 
Discussion of Study Design, Including the Choice of Control Groups 
DMID Protocol 17-0087 is designed as a placebo-controlled double-blinded dose escalation trial with 2 
subjects randomized to placebo and 6 subjects randomized to active drug per cohort. The dose escalation 
design is utilized to confirm the safety of low doses prior to exposing subjects to high doses. Subjects who 
successfully complete Cohort 3 will “rollover” to Cohort 6 after a minimum of 60 days following their first 
dose after completion of Cohort 3. As part of Cohort 6, subjects will be given the study product following a 
high-fat, high-calorie meal to study the safety and PK profiles of VT-1598 and VT-11134, its primary 
metabolite, under a fed state. This is intended to provide a preliminary assessment of whether there is a food 
effect. Comparisons of fed to fasted PK profiles will be exploratory. For comparisons of active drug Dose 
Groups to placebo, a pooled group of placebo subjects across multiple cohorts will be used. The same subjects 
assigned to placebo in Cohort 3 that continue to Cohort 6 will be counted separately within the Placebo Dose 
Group for each dosing period.  
4.3. 
Selection of Study Population 
Only subjects who meet all of the inclusion and none of the exclusion criteria will be eligible for enrollment 
into this study. No exemptions are granted on Inclusion/Exclusion Criteria in DMID-sponsored studies. Up to 
48 healthy male and female subjects, ages 18-45 inclusive, will be enrolled into Cohorts 1 through 6. Neither 
women nor minorities will be excluded from participation in this study. Women of childbearing potential may 
be included as per the inclusion criteria (See inclusion criteria below). Subjects will be recruited without 
regard to gender or race. It is expected that race will reflect that within the community. The demographics in 
the local population should ensure that male and female minorities will be represented in the enrolled 
population.  
Eligibility criteria from v5.0 of the protocol are listed below:  
Inclusion Criteria:  
1. Willing and able to provide written informed consent and authorization for use of protected health 
information; 
2. Willing and able to comply with protocol requirements, instructions, and protocol-stated restrictions 
(including confinement to the clinical research unit (CRU)) and is likely to complete the study as 
planned; 
3. Male and female subjects, 18-45 years of age (inclusive); 
4. Subject is in good health to be safely enrolled in this protocol as determined by medical history and 
physical exam; 
5. BMI of 18-35 kg/m2, inclusive, and minimum weight of 50 kg; 


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6. If a female participant is of childbearing potential*, she must use a highly effective contraceptive
method† from 30 days before enrollment through the 3 months after dosing;
*A woman is considered of childbearing potential unless post-menopausal (subject is at least 50 years
old and has history of > 2 years without menses without other known or suspected cause and has a
follicle stimulating hormone (FSH) level >40 IU/L), or permanently surgically sterilized.
†A highly effective contraceptive method includes surgical sterilization methods such as tubal ligation, 
bilateral oophorectomy, salpingectomy, hysterectomy, or successful tubal obliteration (e.g., Essure®) 
with documented radiological confirmation test at least 90 days after the procedure, or long-acting 
reversible contraception (progestin-releasing subdermal implants, copper intrauterine devices (IUDs), 
levonorgesterel-releasing IUDs. 
7. Males* having sexual intercourse with women of childbearing potential must agree to consistent use
of condoms from study product administration through 3 months after dosing**;
* Including vasectomized men.
** And must also agree to not donate sperm during this same time period. 
8. Subject has adequate venous access for blood collection.
Exclusion Criteria: 
1. Has a chronic condition that may increase risk to subject or interfere with endpoint assessment (e.g.,
liver disease, kidney disease, immunodeficiency);
2. Chronic condition diagnosed within 90 days of the Screening visit;
3. Unstable chronic disease* within 6 months of the Screening visit;
*As defined by need for medical intervention that lead to a change in medications and/or required
hospitalization, surgery/procedure, or Emergency Department/urgent care visit.
4. History of psychiatric condition that has required hospitalization in the last 5 years or patient is
considered unstable by study investigator;
5. Any condition that is in the opinion of the Investigator could significantly impact drug absorption,
distribution, or elimination;
6. Any out of normal range value* at Screening or enrollment (Section 8.1 and Appendix B of the
protocol);
*A laboratory value that is Grade 1 (with the exception of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), Total bilirubin, hemoglobin or serum creatinine) will be allowed if not
considered to be clinically significant by the investigator.
7. Abnormal ECGs. See Section 7.1 of the protocol Clinical Evaluations for exceptions;
8. Electrocardiographic QTcF interval >430 msec for males and >450 msec for females at Screening;
9. Positive test for antibodies to Human Immunodeficiency Virus (HIV)-1, HIV-2, Hepatitis B Surface
Antigen (HBsAg), or Hepatitis C Virus (HCV);
10. Positive urine drug test. The drugs that will be screened for includes amphetamines, barbiturates,
cocaine, opiates, cannabinoids, phencyclidine, and benzodiazepines;


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11. Female subject of childbearing potential who is pregnant*, lactating, or planning to become pregnant
during the study period or 3 months after the final dose of study product;
*Having a positive serum pregnancy test at the Screening Visit or any other specified timepoint prior
to the dose of the study product.
12. Received any study product in a clinical trial within 30 days prior to Screening;
13. Admitted or documented illicit drug use or alcohol abuse within 6 months prior to Screening or during
their participation in the trial;
14. Consumed alcohol within 72 hours of Day -1, until after the visit to the CRU on Day 14 or have
positive alcohol test at Screening or on admission to the CRU;
15. Tobacco* use within 90 days prior to the Screening Visit or while a subject is enrolled in the study OR
a positive drug test for cotinine;
*Tobacco use includes vaping, smoking tobacco, the use of snuff and chewing tobacco, and other
nicotine or nicotine- containing products.
16. Use of prescription drugs within 14 days prior to the dose of study product with the exception of
hormonal contraceptives, which are permitted throughout the study;
17. Received any non-prescription medications, vitamins, or dietary supplements* within 7 days of
dosing, unless prior approval is granted by both the Investigator and the Sponsor;
*Excluded from this list is intermittent use of acetaminophen at doses of <2 g/day or ibuprofen <1200
mg/day. Herbal supplements must be discontinued 7 days prior to the dose of the study product.
18. History of intolerance or hypersensitivity to azole antifungals;
19. Blood donation or other significant blood loss within 60 days of Screening and for the duration of the
study;
20. Inability or difficulty swallowing whole capsules/tablets and/or multiple capsules/tablets;
21. Consumption of beverages and foods containing caffeine for 24 hours prior to Day -1 until discharge
from the CRU on Day 4;
22. Consumption of grapefruit, or juices containing grapefruit or Seville oranges within 7 days prior to the
scheduled dose of the study product until after the visit to the CRU on Day 14;
23. Subject has plans to enroll or is already enrolled in another clinical trial that could interfere with safety
assessment of the investigational product at any time during the study period*;
*Includes trials that have a study intervention such as a drug, biologic, or device.
24. Having dietary restrictions that would preclude the subject from participating in either fed or fasted
cohorts;
25. Having sensitivity or allergy to aspirin.


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4.4. 
Treatments 
4.4.1. 
Treatments Administered 
Subject will receive either a single oral dose of VT-1598 ranging from 40 mg to 640 mg or matching placebo 
tablet(s) according to cohort (Table 1).  
VT-1598 or placebo tablets will be administered orally with approximately 240 mL of ambient temperature 
water on the morning of Day 1. Subjects in fasted cohorts (Cohort 1- 5) will receive the study product after an 
overnight fast of at least 8 hours. Subjects in these cohorts will continue to fast for an additional 4 hours post 
dose. Subjects in Cohort 6 will be dosed at the same level as Cohort 3 on the morning of Day 1. This group 
will not fast and will be fed a high-fat, high-calorie meal which will be entirely consumed within 30 minutes. 
The high-fat, high-calorie test meal will be comprised of a breakfast of approximately 900-1000 calories, with 
approximately 150 calories from protein, 250 calories from carbohydrates, and 500-600 calories from fat.  
The dose of the study product will be administered 30 minutes after the start of the meal.  
4.4.2. 
Identity of Investigational Product(s) 
VT-1598 is a novel oral agent for the treatment of fungal infections and will be supplied as 40 mg and 80 mg 
tablets. VT-1598 in its physical form is a lightly colored solid formulated as a spray-dried dispersion with 
standard excipients including Eudragit® L100, microcrystalline cellulose, mannitol, croscarmellose sodium, 
colloidal silicon dioxide, magnesium stearate, and FD&C Yellow #5 aluminum lake (United States 
Pharmacopeia). 
Placebo will be supplied as matching tablets (40 mg and 80 mg VT-1598 tablets) containing the inactive 
components of VT-1598. To maintain the blind, the placebo tablets will be the same size, weight, and color as 
the VT-1598 tablets.  
Additional details of the investigational products may be found in the study protocol and Manual of 
Procedures (MOP).  
4.4.3. 
 Method of Assigning Subjects to Treatment Groups (Randomization) 
Enrollment/randomization will be performed through the enrollment module in the electronic data capture 
system (EDC), maintained by the Statistical and Data Coordinating Center (SDCC). The randomization 
schedule will be generated centrally through the AdvantageEDCSM (Electronic Data Capture System, Emmes) 
by the unblinded study biostatistician and a list will be transferred to the unblinded study pharmacist prior to 
the start of the study for the purpose of an emergency back-up. AdvantageEDC will assign each subject to a 
treatment arm after the demographic and eligibility data have been entered into the system. Randomization for 
the study is described below.  
In Cohort 1 through Cohort 5, 8 subjects will be randomized in a 3:1 ratio to active drug and placebo. The 
first 2 subjects will be sentinel subjects and will be randomized in a 1:1 ratio to active drug and placebo, to 
ensure that one of the first 2 subjects receive active drug and the other receives placebo for sentinel dosing. 
The study product assigned to the remaining 6 subjects in Cohorts 1 through 5 will be randomly assigned in a 
5:1 ratio of active drug to placebo to ensure the 3:1 ratio for the entire dosing cohort. Enrollment will occur at 
one site and randomization will not be stratified.  
After completing the final study visit (Day 21) and at least 60 days after dosing, Cohort 3 subjects will have 
enrollment “rollover” to Cohort 6. Cohort 3 subjects continuing as Cohort 6 subjects will not be randomized 
but will receive the same assignment as they received in Cohort 3: A subject will receive placebo if he or she 


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received placebo as part of Cohort 3, otherwise the subject will receive 160 mg of VT-1598. There will be no 
sentinel subjects in Cohort 6. 
An appropriate number of back-up subjects will be screened per cohort in the event that subject replacement 
is needed. Subjects who discontinue from study participation without receiving any amount of study product 
may be replaced. Subjects who experience emesis within the first 12 hours after dosing may also be replaced. 
The first subject in each cohort to discontinue from participation due to loss to follow up after receiving any 
amount of study product will not be replaced in that cohort. If more than one subject in any cohort 
discontinues participation, these additional subjects after the first subject will be replaced. Replacement 
subjects will receive the same study product as the subject they are replacing.  
Subjects who complete Cohort 3 but become ineligible or withdraw prior to dosing for Cohort 6 will be 
replaced. Subjects in Cohort 6 who do not finish the high-fat high-calorie meal within 30 minutes will not be 
dosed and will be replaced. Cohort 6 replacement subjects will receive the same study product as assigned to 
the Cohort 3 subject they are replacing. Cohort 6 may start enrolling prior to convening the SMC meeting and 
prior to the start of Cohort 5. 
4.4.4. 
Selection of Doses in the Study 
See Sections 2.1 and 2.2 of the study protocol v5.0 for rationale of dose selection. Further details may be 
found in the Investigational Brochure [4].  
4.4.5. 
Selection and Timing of Dose for Each Subject 
Study product for each subject will be assigned by randomization and will not be further adjusted. Subjects in 
the fasted cohorts (Cohorts 1-5) will receive the study product in the morning by mouth after an overnight fast 
of at least 8 hours. Subjects will remain fasted for at least 4 hours post dose. The wash-out period for Cohort 3 
subjects who continue to Cohort 6 will be a minimum of 60 days following the first dose after completion of 
Cohort 3 to allow for adequate time to eliminate the effect of study product prior to dosing in Cohort 6. 
Subjects in the fed cohort (Cohort 6) will fast overnight for at least 8 hours prior to the start of a high-fat, 
high-calorie meal, which will be entirely consumed in less than 30 minutes. The study product will be 
administered 30 minutes after the start of the meal. No other food will be ingested until after a minimum of 4 
hours post dose.  
4.4.6. 
Blinding 
This is a double-blind clinical study. The VT-1598 and placebo tablets and packaging will look identical to 
maintain the blind for the subject and study staff administering the treatment.  
Subjects, investigators, study staff administering drug, study personnel performing any study-related 
assessments, bioanalytical laboratory personnel, and Fisher repository personnel will be blinded to subject 
treatment assignments throughout the study. The DMID medical monitor and National Institute of Allergy 
and Infectious Diseases (NIAID) personnel will remain blinded to all subject randomization assignments. 
Selected individuals not involved in the conduct of the study, including members of the SMC, may have 
access to unblinded data as needed for safety review or other data review. The randomization scheme will be 
provided to the unblinded study personnel (study pharmacist preparing the study product and verifier) only for 
emergency unblinding purposes. Emergency unblinding of treatment assignment for a subject may be 
necessary due to a medical emergency or other significant medical event. Procedures for emergency 
unblinding are detailed in the MOP. The treatment assignment code list will be kept in a secure place at all 
times.  


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4.4.7. 
Prior and Concomitant Therapy 
Prior drugs and medications taken, including non- prescription and herbal products, will be recorded at 
Screening for the previous 30 days for each subject. At each subsequent study visit, including enrollment, 
each new concomitant medication and changes to existing medications will be recorded in the subject’s 
source documents and on the appropriate electronic case report form (eCRF). Prior and concomitant 
medications will be listed in Listing 8 and Listing 9, respectively. 
See Section 7.1.2 of the study protocol v5.0 for restrictions regarding prior and concomitant therapies. 
4.4.8. 
Treatment Compliance 
Study product will be administered at the ICON Early Phase Services by site personnel in accordance with 
assigned randomization. Subject compliance is not anticipated to be an issue. Complete information regarding 
any partial or interrupted dosing will be documented. Start and end times of dosing, times of last food and 
fluid ingestion before dosing, and first food and fluid ingestion after dosing will be recorded on the 
appropriate eCRF. Within 5 minutes of product administration, study personnel will examine the oral cavity 
of each subject to assure that all study product was swallowed.  
4.5. 
Safety and Pharmacokinetic Variables 
The following section describes the safety and PK endpoints of the study. As this study is a Phase 1 clinical 
trial in healthy adult subjects, there will be no assessment of drug efficacy. For a detailed schedule of study 
procedures refer to Table 2. Refer to Section 3 for a list of the primary and secondary objectives and 
endpoints. For definitions of baseline for safety endpoints, refer to Section 3.3.4.  
Incidence, relatedness, and severity of treatment-emergent AEs and SAEs will be recorded from the time of 
dosing to the final visit on the appropriate eCRF. All AEs will be graded for severity and the relationship to 
the study product by a trained and qualified member of the study team as described in Sections 8.1 and 8.2 of 
the study protocol v5.0. AEs and SAEs are defined in Sections 8.1 and 8.2 of the study protocol v5.0. 
Clinical AEs will be graded using the toxicity grading scales in Table 3.  
Clinical laboratory results, VS, and ECG results will be assessed using the toxicity grading scales in Table 4, 
Table 5, and Table 6 , respectively. 
In addition to AEs, the following safety endpoints will be assessed according to the study procedure listed in 
Table 2:  
•
CHEM, HEM, and COAG clinical laboratory result safety parameters:
-
The results will be graded according to the toxicity grading criteria in Table 4.
-
The following parameters will be measured:
o
CHEM parameters: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium,
chloride, total protein, creatinine, triglycerides, total cholesterol, low-density lipoprotein
cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total carbon dioxide, creatine
phosphokinase, phosphorus, alkaline phosphatase, AST, ALT, total bilirubin, direct bilirubin,
magnesium, gamma-glutamyl transferase (GGT), and serum cortisol.
o
HEM parameters: hemoglobin, hematocrit, differential white blood cell count (lymphocytes,
neutrophils, monocytes, eosinophils, basophils), platelet count, red blood cell count (RBC),
and total white blood cell count (WBC).


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o
COAG parameters: Prothrombin time, Activated partial thromboplastin time (PTT), and
international normalized ratio.
o
UA parameters: specific gravity by dipstick, pH by dipstick, occult blood by dipstick,
leukocyte esterase by dipstick. If dipstick urinalysis testing is abnormal, RBC by complete UA
and WBC by complete UA will be assessed. Urinalysis WBC count will be measured but the
results will not be graded for toxicity.
•
VS parameters:
-
VS will be obtained after subjects have rested for at least 5 minutes.
-
VS parameters will be graded according to the toxicity grading criteria in Table 6.
-
Subjects with a history of sinus bradycardia will only have AEs of moderate severity or greater 
entered for bradycardia/decreased heart rate.
-
The following parameters will be measured:
o
Systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, and temperature.
•
ECG parameters:
-
ECG measurements will be conducted in triplicate, and the mean of triplicate values will be used 
for analysis, including analyses of change from baseline.
-
All ECG triplicate readings will be conducted at least 1 minute apart within a 15-minute period.
-
ECG results will be read by the study PI or a designated clinician and graded according to the 
toxicity grading criteria in Table 6. For each timepoint, overall interpretation of the ECG will be 
reported as Normal; Abnormal, Not Interpretable; or Abnormal, Clinically Significant (CS). 
Evaluation of rhythm, arrhythmia, conduction disturbance, axis, myocardial infarction, ST 
segment, and other abnormal findings will also be assessed.
-
If QTcF prolongation occurs after dosing then telemetry monitoring will start, and triplicate 12-
lead ECGs will be captured every 30 minutes until the average for the triplicates has returned to 
within 60 ms of the baseline value.
-
The following parameters will be measured:
o
PR interval, QRS duration, QT interval, QTcF interval, RR interval, and mean ventricular heart 
rate.
o
Prior to 16NOV2020 QTc interval was included in the ECG parameters measured. Because 
QTc and QTcF are similar intervals, the study team determined that QTc should be removed 
from the eCRF so as to reduce redundant data collection. QTcF was kept as the interval as it is 
the parameter referenced in the Inclusion and Exclusion criteria.
•
Physical exams:
-
Complete physical exams include the following parameters:
o
General appearance; head, eyes, ears, nose, and throat; neck; chest and lungs; cardiovascular 
system, abdomen, and musculoskeletal system, lymph nodes, extremities/skin, and neurological 
system.
-
Targeted physical exams include the following parameters:


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o
General appearance, heart, lungs, skin, abdomen.
Blood and urine samples for PK analysis will be collected according to the study procedures listed in Table 
2. VT-1598 and VT-11134 concentrations will be measured from plasma and urine samples. The 
bioanalytical lab, ICON Bioanalytical Laboratory (ICON BAL) will analyze VT-1598 and VT-11134 
concentrations using the validated liquid chromatography/tandem mass spectrometry assays (LC-MS/MS).  


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5.
SAMPLE SIZE CONSIDERATIONS
This is a Phase 1 FIH study to assess the safety and PK of VT-1598. Since the study is primarily aimed at 
safety and PK evaluation, no formal power calculations based on testing a statistical hypothesis were 
constructed. The sample size of 8 subjects (6 subjects receiving VT-1598 and 2 subjects receiving placebo) 
per cohort is based on clinical experience and judgement and should provide adequate clinical information to 
meet the study objectives. The comparisons of PK between the fasted and fed cohorts (Cohort 3 and Cohort 6) 
are exploratory rather than formal analyses of fed bioequivalence. Fasted and fed PK profiles from 6 subjects 
are sufficient to meet the intended purpose.  


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6.
GENERAL STATISTICAL CONSIDERATIONS
6.1. 
General Principles
Summary statistics for continuous data will include the number of subjects included in analysis (N), mean, 
standard deviation (SD), median, minimum value (min), and maximum value (max). Summary statistics for 
discrete data will include frequencies and proportions and may include confidence intervals (CIs) for the 
proportion. When 95% CIs are given for a proportion, exact (Clopper-Pearson) CIs will be used, unless 
otherwise specified. All randomized subjects will be included in the summaries of subject demographics. The 
Safety Population will be used for summaries of safety endpoints and the PK Analysis Population or the PK 
Analysis Subset will be used for summaries of PK endpoints. 
Denominators for safety endpoints will be the number of subjects in the Safety Population. Denominators for 
clinical laboratory, VS, and ECG results at planned study timepoints will be the number of subjects with 
available results at the specified timepoint for that parameter. Denominators for the conceptual “Maximum 
Severity Post Baseline” timepoint for clinical laboratory, VS, and ECG results will be the number of subjects 
with an observed result for the parameter obtained post dose.  
The sort order for listings is indicated in the implementation note for each listing shell (Appendix 3). The sort 
order of clinical laboratory tests, VS, and ECG parameters is described in Section 9.  
All safety and PK analyses will be performed by Dose Group as described in Section 3.3.2. 
6.2. 
Timing of Analyses 
The final analysis will be performed after database lock. 
An interim PK analysis is planned between Cohort 3 and Cohort 4. Enrollment for Cohort 4 will not depend 
on the PK interim analysis.  
The SMC will review data at the following times: 
•
Between Cohort 4 and Cohort 5
•
After completion of dosing and final visit for all cohorts
•
Ad hoc meeting(s): as required in response to halting criteria (Protocol section 8.6) being met for
sentinels, dose escalation, or the overall study, or at the request of DMID to review a potential safety
concern identified by either the PI, medical monitor, participating investigator, or the independent
safety monitor (ISM) .
6.3. 
Analysis Populations 
All analysis populations to be used in the final analysis are described in this section. A tabular listing of all 
randomized and enrolled subjects excluded from an analysis population (Safety Population or a PK Analysis 
Population) will be included in the CSR (Listing 5). In the case there are multiple reasons for exclusion from 
the PK Analysis Population or PK Analysis Subset, only one reason will be counted when summarizing 
reasons for exclusion from analysis populations in Table 10. 
6.3.1. 
Safety Population 
The Safety Population will include all subjects that received any amount of study product and will be 
analyzed by Dose Group. Placebo subjects will be pooled across multiple cohorts for analysis. Placebo 


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subjects enrolled in Cohort 3 that continued on to Cohort 6 will be counted separately for each study part, as 
detailed in Section 3.3.2. 
6.3.2. 
PK Analysis Population 
The PK Analysis population will consist of all subjects who received VT-1598 and have at least 1 quantifiable 
post dose plasma or urine sample with measurable drug or metabolite concentration. Subjects who 
participated in both Cohort 3 and Cohort 6 will be evaluated and included separately per dosing period for 
inclusion into the PK Analysis Population; i.e., subjects will be included in the PK Analysis Population once 
under a Fasted state and once again under a Fed state. Similarly, results from these subjects will be analyzed 
separately per dosing period. Subjects enrolled and randomized to receive some dose of VT-1598 who did not 
complete his or her dose, or otherwise received an incorrect dose will not be included in the respective Dose 
Group for analysis. However, listings will include concentrations and parameter estimates for those subjects. 
Regardless of the subject’s inclusion in the PK Analysis Population, all VT-1598 and VT-11134 
concentration results will be included in listings, including results from placebo subjects. The order that 
reasons will be considered for a PK Analysis Population will be: the subject received placebo, the assigned 
dose was not received or completed, the subject has no measurable drug or metabolite concentration in plasma 
or urine. 
6.3.2.1. 
PK Analysis Subset 
The PK Analysis Subset will be based on the PK Analysis Population and will include all subjects who 
completed the PK part of the trial in each dosing period without any protocol deviation that would likely 
affect the PK results and who have an evaluable plasma or urine concentration for either VT-1598 or VT-
11134 from which at least a subset of the designated PK parameters can be determined. The order that reasons 
will be considered for a PK Analysis Subset will be: excluded from the PK Analysis Population, occurrence 
of protocol deviation(s) with potential to impact PK, PK data is insufficient to estimate any plasma or urine 
PK parameters. 
6.4. 
Covariates and Subgroups 
The protocol does not define any formal subgroup analyses. 
6.5. 
Missing Data 
All attempts will be made to collect data per protocol. Any missing data or data anomalies will be 
communicated to the study site for clarification and resolution. Missing collection times for blood and urine 
PK samples may be imputed as the nominal time if the sample was confirmed to be collected within the 
protocol defined window. No further imputation of missing data is planned.  
6.6. 
Interim Analyses and Data Monitoring 
An SMC meeting to review safety data is planned between Cohort 4 and Cohort 5. Safety data, including 
AEs; SAEs; clinical laboratory results (CHEM, HEM, COAG, and UA); VS, and 12 lead ECGs will be 
presented by cohort. Reasons for subjects who terminate the study early or discontinue treatment will be 
presented for all cohorts. The SMC may also review safety data by Dose Group in the closed session or ad 
hoc meetings as requested. An interim analysis of PK data is planned following the completion of Cohort 3. 
The interim PK report will only show PK data in aggregate and will not include any potentially unblinding 
information. The interim PK analysis will be conducted on the PK Analysis Population and will present 


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concentration and estimated PK parameter results for both specimen types by Dose Group and analyte. 
Further details of the interim PK analysis are provided in the Interim Noncompartmental PK Analysis Plan 
for the study [6].  
6.7. 
Multicenter Studies 
This is a single-site study. 
6.8. 
Multiple Comparisons/Multiplicity 
This is a Phase 1 FIH study with multiple primary endpoints. Because analyses of primary endpoints are 
descriptive rather than hypothesis tests, no adjustments for multiple testing are planned.  


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7.
STUDY SUBJECTS
7.1. 
Disposition of Subjects
Screened subjects who were ineligible for enrollment in the study (screen failures) or eligible but not 
enrolled will be summarized by inclusion and exclusion criteria (Table 11). Enrolled subjects who were 
ineligible for inclusion in analysis populations will be summarized by reason for subject exclusion and Dose 
Group 
(Table 10). Individual listings of subjects who were excluded from the Safety Population or a PK Analysis 
population will be listed (Listing 5).  
Subject disposition will be summarized (Table 9), showing the number of subjects who were screened, 
enrolled and randomized, received study product, completed all planned PK blood draws, completed all 
planned PK urine samples, completed final study visit, participated in the fast and fed cohorts (for Cohort 3 
and Cohort 6), and terminated early.  
Subjects who discontinued dosing or terminated early from the study will be listed (Listing 2). 
A flowchart displaying the disposition of study subjects will be included (Figure 2). This figure will present 
the number of subjects screened, enrolled, lost to follow-up, and analyzed by Dose Group.  
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by deviation category, deviation type, 
and Dose Group (Table 8). This table will provide both the number of subjects and the number of deviations 
for each deviation category and deviation type. All subject-specific protocol deviations and non-subject-
specific protocol deviations will be listed in Listing 3 and Listing 4, respectively. 


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8. 
EFFICACY EVALUATION 
There are no efficacy endpoints for this trial.  


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9. 
SAFETY EVALUATION
All safety analyses will be performed using the Safety Population and will be presented by Dose Group. 
Placebo subjects enrolled in Cohort 3 that continued on to Cohort 6 will be counted separately for each dosing 
period, as detailed in Section 3.3.2. 
Any medical condition that is present at the time that the subject is screened will be considered baseline and 
not reported as an AE, unless it worsens in severity or increases in frequency during the study. The 
denominators for proportion values will be indicated within the table or table header. AEs will be summarized 
for the number of subjects who experienced an AE and the number of events by Dose Group and Medical 
Dictionary for Regulatory Activities (MedDRA)  category. Toxicity grading scales for clinical adverse 
events are provided in All reported AEs will be included in the summaries and analyses.  
Clinical laboratory, VS, and ECG results will also be used to assess safety. Results from these assessments 
will be graded by severity and presented in tables and figures by Dose Group for each post baseline 
timepoint. The analysis timepoints that will be summarized are presented in Table 7. The most extreme 
severity grade observed after dosing will be summarized (Maximum Severity Post Baseline) and will include 
results from unscheduled visits. For tabular displays of clinical laboratory, VS, and ECG results by parameter, 
the maximum severity across all parameters within each category (CHEM, HEM, COAG, UA, VS, and ECG) 
will be included and summarized by timepoint (Any Parameter). CHEM, WBC (in COAG), and VS 
parameters will be displayed by event direction (increase or decrease).  
9.1. 
Demographic and Other Baseline Characteristics 
Sex, ethnicity, and race of all subjects will be summarized by Dose Group (Table 12). Ethnicity will be 
categorized “Hispanic or Latino,” or “Not Hispanic or Latino,” “Unknown,” or “Not Reported.” In 
accordance with National Institutes of Health (NIH) reporting policies, subjects may self-designate as 
belonging to more than one race or may refuse to identify a race, the latter reflected in the case report form 
(CRF) as “No” to each race option. Age at enrollment, height, weight and BMI at Screening will be 
summarized by Dose Group (Table 13). Individual subject listings will be presented for all demographic 
and baseline characteristics (Listing 6).  
9.1.1. 
Prior and Concurrent Medical Conditions 
All current illnesses and past pre-existing medical conditions will be MedDRA coded using MedDRA 
dictionary version 23.1 or higher. Summaries of subjects’ pre-existing medical conditions by MedDRA 
system organ class (SOC) will be presented by Dose Group (Table 14). Individual subject listings will 
be presented for all medical conditions (Listing 7).  
9.1.2. 
 Prior and Concomitant Medications 
All medications will be coded to the Anatomical Therapeutic Classification (ATC) using the current version 
of the WHO Drug Dictionary. The use of prior and concomitant medications taken during the study will be 
summarized by ATC 1 and ATC 2 (separately, in Table 15 for prior medications and Table 16 for 
concomitant medications). Individual subject listings will be presented for all prior medication (Listing 8) and 
concomitant medications (Listing 9).  
Regardless of the certainty of the date entered, drugs will be listed and summarized as prior medications when 
the end date for the medication is before study product administration and listed and summarized as 


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concomitant medications otherwise. If a medication has no recorded end date it will be considered a 
concomitant medication. 
9.2. 
Measurements of Treatment Compliance 
Date and time of study product administration, along with information on whether the subject was dosed 
according to protocol will be included in Listing 10. Subject level drug and metabolite concentrations at 
each timepoint will be included in Listing 30 for plasma and Listing 31 for urine.  
9.3. 
Adverse Events 
When calculating the proportions of subjects with AEs within a given MedDRA category, subjects will be 
counted once for each dosing period within the same MedDRA category, and the event will be reported 
according to the highest severity recorded throughout the indicated time period (separately for related and 
unrelated AEs when both severity and relatedness are tabulated). Repeated AEs will be ignored. When 
calculating the number of AEs that occurred, all AEs will be summarized by Dose Group, including 
repetitions. 
All reported adverse events will be included in the summaries and analyses. 
9.3.1. 
Solicited Events and Symptoms 
No solicited events will be collected in this trial. 
9.3.2. 
Unsolicited Adverse Events 
An overall summary of unsolicited AEs by Dose Group will be presented in Table 17 including the number 
of subjects with at least one AE, number of subjects with at least one related AE, and number of subjects with 
at least one SAE.  
All AEs will be presented in Listing 11. A subject listing of non-serious AEs of moderate or greater severity 
will also be reported (Table 22).  
Denominators for proportions are the number of subjects in the Safety Population in each Dose Group. 
Placebo subjects who participated in both Cohort 3 and Cohort 6 will contribute to the denominator once per 
each dosing period for the Placebo Dose Group. Subjects who received VT-1598 and participated in both 
Cohort 3 and Cohort 6 will contribute to the denominator once per each dosing period for the Any Dose 
Group. The following summaries for unsolicited AEs will be presented:  
•
The number of AEs and number and proportion of subjects reporting an AE or SAE that occurred in 
5% of all subjects along with the total number of events reported will be presented by Dose Group, 
SOC, HLGT, and preferred term (PT) (Table 18).
•
The number of AEs and number and proportion of subjects reporting an AE will be presented by Dose 
Group, SOC, HLGT, and PT. The 95% CI for the proportion of subjects experiencing each
SOC/HLGT/PT will also be presented (Table 19).
•
The number and proportion of subjects reporting a related or unrelated AE will be presented by Dose 
Group, SOC, HLGT, PT, severity, and relationship to study product. (Table 20)
Summaries of unsolicited AEs will be presented graphically in bar charts by Dose Group and SOC. For 
summaries of proportions of subjects reporting an AE, denominators will be the number of subjects in the 
Safety Population for each Dose Group. Placebo subjects who participated in both Cohort 3 and Cohort 6 will 


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contribute to the denominator once per each dosing period. Subjects who received VT-1598 and participated 
in both Cohort 3 and Cohort 6 will contribute to the denominator once per each dosing period for the Any 
Dose Group:  
•
The proportion of subjects reporting a related AE will be presented by the maximum severity reported 
per SOC (Figure 3).
•
The total number of related AEs reported will be presented by Dose Group and SOC (Figure 4).
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events 
Individual data listings of deaths and other SAEs will be provided (Table 21). The listing will include subject 
ID, Dose Group, AE description, SOC, High-Level Group Term (HLGT), PT, duration of AE, reason reported 
as an SAE, severity, relationship to treatment, alternate etiology if not related, action taken with study 
treatment, whether the subject discontinued due to the AE, and AE outcome.  
9.5. 
Pregnancies 
Individual data listings of pregnancy reports will be provided if a pregnancy occurs post dosing: 
•
Maternal information will be presented in Listing 24.
•
Gravida and para information will be presented in Listing 25.
•
Live birth outcomes will be presented in Listing 26, and still birth outcomes will be presented in 
Listing 27.
•
Spontaneous, elective, or therapeutic abortion outcomes will be presented in Listing 28.
Birth control method(s) will be listed for each subject with a start and end date (Listing 29). 
9.6. 
Clinical Laboratory Evaluations 
Toxicity grading criteria for clinical laboratory results can be found in Table 4. Unscheduled clinical 
laboratory evaluations will be included in listings of all clinical laboratory results, but excluded from tabular 
and graphical summaries by timepoint, except when calculating the maximum severity post baseline. Any pre-
existing abnormal lab results at Screening and Baseline will be graded and presented in listings but will not be 
reported as an AE unless it is treatment-emergent (i.e. severity worsens after dosing). Clinical laboratory 
parameters that have grading criteria for both decreases (result lower than normal range) and increases (result 
higher than normal range) will be summarized separately by direction. Descriptions of each clinical laboratory 
summary are described below:  
The following laboratory parameters will be presented (in order): 
•
CHEM: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium, chloride, total protein,
creatinine, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, total carbon dioxide,
creatine phosphokinase, phosphorus, magnesium, GGT, alkaline phosphatase, AST, ALT, total
bilirubin, direct bilirubin, and serum cortisol.
•
HEM: hemoglobin, hematocrit, lymphocytes, neutrophils, monocytes, eosinophils, basophils, platelet
count, RBC, and WBC.
•
COAG: prothrombin time, PTT, and international normalized ratio.


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•
UA: specific gravity by dipstick, pH by dipstick, occult blood by dipstick, leukocyte esterase by
dipstick, RBC by complete UA, and WBC by complete UA (microscopic tests to be completed if
dipstick urinalysis is abnormal). If microscopic results were obtained in the absence of an abnormal
dipstick result (or without dipstick tests being done), results of the complete urinalysis or microscopy
will still be summarized.
All safety laboratory results, severity, and change from baseline will be listed for each subject by Dose Group 
and timepoint. Abnormal laboratory results (laboratory results outside the normal range defined in the MOP) 
will be presented. Abnormal laboratory results that do not have toxicity grading ranges defined in the protocol 
will not have severity indicated in tables and listings of abnormal laboratory results, except as “ONR” (out of 
normal range). 
•
All CHEM results, including unscheduled visits, will be presented in Listing 12. Abnormal results will 
be presented in Table 23.
•
All HEM results, including unscheduled visits, will be presented in Listing 13. Abnormal results will 
be presented in Table 24.
•
All COAG results, including unscheduled visits, will be presented in Listing 14, Abnormal results will 
be presented in Table 25.
•
All UA results, including unscheduled visits, will be presented in Listing 15. Abnormal results will be 
presented in Table 26.
All Screening results will be listed for each subject by Dose Group and visit: 
•
Serology results (Listing 16).
•
Urine toxicology and alcohol urine results (Listing 17).
•
Serum human chorionic gonadotropin (hCG) and pregnancy testing results (Listing 18).
Laboratory results will be summarized in tables and figures: 
•
Proportion of subjects with anormal laboratory results by parameter, Dose Group, and timepoint for 
CHEM (Table 27), HEM (Table 30), COAG (Table 33), and UA (Table 36).
•
Proportion of subjects with mild, moderate, or severe laboratory results by parameter, Dose Group, 
and timepoint for CHEM (Table 28), HEM (Table 31), COAG (Table 34), and UA (Table 37).
•
Summary statistics of change from baseline by parameter, Dose Group, and timepoint for CHEM
(Table 29), HEM (Table 32), COAG (Table 35), and UA (Table 38). UA character results (i.e. “1+”) 
will be excluded from change from baseline summaries.
•
Graphical presentation of change from baseline at scheduled visits by Dose Group, and timepoint for 
each parameter as a series of box plots.
o
CHEM parameters will be presented beginning at Figure 5 and continuing through Figure 28.
o
HEM parameters will be presented beginning at Figure 29 and continuing through Figure 38.
o
COAG parameters will be presented in for PTT (Figure 39), PT (Figure 40), and international 
normalized ratio (Figure 41).
o
UA parameters presented include specific gravity (Figure 42) and pH (Figure 43).


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9.7. 
Vital Signs and Physical Evaluations 
Toxicity grading criteria for VS results can be found in Table 5. Unscheduled VS measurements will be 
listed, but excluded from tabular and graphical summaries by timepoint, except when calculating the 
maximum severity post baseline. If VS measurements are repeated due to technical errors, the initial 
measurements made in error will not be used for analysis but will be listed. Baseline is defined as the last VS 
measurement taken before dosing on Day 1.  
VS parameters that have grading criteria for both decreases (result lower than normal range) and increases 
(result higher than normal range) will be summarized separately by direction.  
The following VS parameters will be presented (in order): systolic blood pressure, diastolic blood pressure, 
pulse, respiratory rate, temperature. 
VS results will be summarized in tables and figures: 
•
Proportion of subjects with mild, moderate, or severe VS results by parameter, Dose Group, and 
timepoint (Table 39).
•
Summary statistics of change from baseline by parameter, Dose Group, and timepoint (Table 40).
•
Graphical presentation of change from baseline by parameter, Dose Group, and timepoint (beginning 
at Figure 44 and continuing through Figure 58).
All VS measurements, including height, weight, and BMI, will be presented in Listing 19 
Abnormal physical exam findings will be presented in Listing 20.  
9.8. 
12-Lead Standard Electrocardiogram
ECG measurements will be conducted in triplicate; the mean of triplicate values will be used for analysis, 
including change from baseline analysis. Toxicity grade criteria for 12-lead standard ECG parameters 
(mean of triplicate QTcF interval only) can be found in Table 6. Unscheduled 12-lead standard ECG 
measurements will be listed but excluded from tabular and graphical summaries by timepoint, except when 
calculating maximum severity post baseline. Individual interval measurements and overall interpretations 
will be presented in Listing 21 and Listing 22, respectively. Other ECG findings will be presented in Listing 
23.  
The following ECG parameters will be presented (in order): PR interval, QRS Duration, QT interval, QTcF 
interval, RR interval, and mean ventricular heart rate.  
12-lead standard ECG results will be summarized in tables and figures:
•
Summary of 12-lead standard ECG change in overall interpretation from baseline will be shown by 
Dose Group and timepoint (Table 41).
•
Proportion of subjects with mild, moderate, or severe 12-lead standard ECG results will be presented 
for QTcF interval by Dose Group, timepoint, and severity (Table 42).
•
Summary statistics of 12-lead standard ECG change from baseline results will be shown by parameter, 
Dose Group, and timepoint (Table 43). A categorical summary of QTcF by Dose Group and timepoint 
will be presented in (Table 44).
•
Graphically, 12-lead standard ECG change from baseline results will be presented by parameter, Dose 
Group, and timepoint. PR interval will be presented in Figure 59, QRS interval will be presented in 
Figure 60, QT interval will be presented in Figure 61, QTcF interval will be presented in Figure 62,


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RR interval will be presented in Figure 63, and mean ventricular heart rate will be presented in 
Figure 64.  
9.9. 
Other Safety Measures 
No additional safety measures are planned.  


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10.
PHARMACOKINETICS
10.1. 
Graphical and Tabular Summaries of Pharmacokinetic Profiles 
The PK Analysis Subset will be used when summarizing plasma and urine PK concentrations. For both 
measured analytes in each specimen type, concentrations below the limit of quantification (BQL) collected 
before the first measurable PK concentration above the lower limit of quantification (LLOQ) will be treated as 
0 for plotting and for all calculations including noncompartmental analysis (NCA) and concentration 
summary statistics. All other BQL values, for each analyte within each specimen type, observed after the first 
measurable concentration will be treated as missing. There will be no imputation of missing concentrations. 
The geometric mean (GM) of concentrations will be treated as missing for sets of data points containing a 
BQL value.  
Collection of plasma or urine samples outside of the protocol defined time window for the timepoint will not 
result in exclusion of the sample result from NCA. Plasma or urine samples collected out of window will be 
evaluated on a case by case basis. Results from PK plasma samples that were collected substantially outside 
of the protocol defined time window will be excluded from concentration summary statistics by nominal 
timepoints and plots of mean concentration by nominal timepoint. Substantially out-of-window samples are 
defined to be twice the size of the protocol required windows: ± 10 minutes of the nominal timepoint for the 
0.5 h post dose sample; ± 20 minutes of the nominal timepoint for the remaining post dose samples on Day 1; 
± 1 hour of the nominal timepoint for the remaining inpatient days, Day 2, Day 3, and Day 4; ± 2 days for the 
follow-up visits, Day 7 and Day 14; and  ± 4 days for the final study visit, Day 21.  
If the exact time of plasma PK sample collection is not recorded then the collection time will be imputed as 
the planned time for analysis, as long as it is not known that the sample was collected outside of the protocol 
defined window. If the start and/or end time of a urine PK sample is unknown then the missing time(s) will be 
assumed to be the planned sample collection time (start or end), as long as it is not known that the sample was 
collected outside of the protocol defined window. If the exact collection time is not known for either sample 
type, but it is known that the sample was collected outside of the protocol defined time window, then the 
timepoint may be excluded from analysis at the discretion of the PK analyst. Rationale for excluding results 
from analysis will be described in the CSR. Results from samples with imputed collection times will be 
indicated in listings of PK sample concentrations. 
All subjects who have at least one quantifiable concentration of VT-1598 or VT-11134 measured will be 
included in the PK Analysis Population. The bioanalytical laboratory will report VT-1598 and VT-11134 
concentrations in plasma and urine in units of ng/mL. Concentrations in plasma and urine will be reported in 
the same units in the CSR, while cumulative amounts excreted into urine will be reported in units of mg. Drug 
and metabolite concentrations in plasma and urine will be summarized by Dose Group and listed by subject: 
•
Subject level concentrations of VT-1598 and VT-11134 in plasma (Listing 30) and in urine
(Listing 31).
•
Subject specific plasma PK parameters for VT-1598 (Listing 32) and for VT-11134 (Listing 33).
•
Subject specific urine inpatient PK parameters (Listing 34) and urine nominal collection time interval 
PK parameters (Listing 35) for VT-1598 and for VT-11134 (Listing 36 and Listing 37).
Subject level PK concentration listings will include separate columns for concentrations reported by the lab 
and concentrations used for analysis. The lab reported concentrations may include codes, such as: “BQL” or 
“QNS” (Quantity not Sufficient), while the analysis concentrations will contain numeric data only, including 
imputed values such as 0 for pre-dose timepoints and BQL samples prior to the first quantifiable sample. 


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Listings will also indicate the nominal time (i.e., the planned time) and actual post dose time in hours 
associated with the sample and will note sample times which were collected out of window, substantially out 
of window, or imputed. 
Individual and PK concentrations will be presented in tables and figures by Dose Group and nominal 
timepoint: 
•
The GM and coefficient of variation (CV) of individual concentrations in plasma will be presented 
tabularly by Dose Groups for both VT-1598 (Table 45 for sampling times between 0 and 14 hours post 
dose and Table 46 for sampling times between 24 and 480 h post dose) and VT-11134 (Table 57 for 
sampling times between 0 and 14 hours post dose and Table 60 for sampling times between 24 and 480 
hours post dose).
•
Individual concentrations in plasma and summary statistics will be presented tabularly for each Dose 
Group for VT-1598 (beginning at Table 47 and continuing through Table 58) and for VT-11134
(beginning at Table 59 and continuing through Table 72).
•
Individual concentrations in plasma will be presented graphically during the inpatient sampling time 
period (0 h, 0.5 h, 1 h, 1.5 h, 2 h, 3, h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 24 h, 36 h, 48 h, 60 h, 72 h post 
dose). For VT-1598, the 40 mg, 80 mg, 320 mg, and 640 mg Dose Groups will be presented in Figure 
65 and the 160 mg fasted and 160 mg fed Dose Groups will be presented in Figure 66. For VT-11134, 
the 40 mg, 80 mg, 320 mg, and 640 mg Dose Groups will be presented in Figure 69 and the 160 mg 
Fasted and 160 mg Fed Dose Groups will be presented in Figure 70.
•
Individual concentrations in plasma will be presented graphically over all sampling timepoints. For 
VT-1598, the 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups will be presented in Figure 67 
and the 160 mg Fasted and Fed Dose Groups will be presented in Figure 68. For VT-11134, the 40 mg, 
80 mg, 320 mg, and 640 mg Fasted Dose Groups will be presented in Figure 71 and the 160 mg Fasted 
and Fed Dose Groups will be presented in Figure 72.
•
Semi-log individual concentration profiles in plasma will be presented graphically during the inpatient 
sampling time period. For VT-1598 the 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups will 
be presented in Figure 77 and the 160 mg Fasted and Fed Dose Groups will be presented in Figure 78. 
For VT-11134 the 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups will be presented in Figure 
81 and the 160 mg Fasted and Fed Dose Groups will be presented in Figure 82.
•
Semi-log individual concentration profiles in plasma will be presented graphically over all sampling 
timepoints. For VT-1598 the 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups will be 
presented in Figure 79 and the 160 mg Fasted and Fed Dose Groups will be presented in Figure 80. For 
VT-11134 the 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups will be presented in Figure 83 
and the 160 mg Fasted and Fed Dose Groups will be presented in Figure 84. Individual cumulative 
amounts excreted into urine and will be presented graphically for VT-1598 (40 mg, 80 mg, 320 mg, 
and 640 mg Fasted Dose Groups in Figure 73 and 160 mg Fasted and Fed Dose Groups in Figure 74) 
and VT-11134 (Figure 75 and Figure 76).
•
Graphically, plots of mean concentration in plasma profiles will be presented with error bars 
representing ± 1 SD around each sample timepoint for both VT-1598 (Figure 85 for 0 h to 72 h post 
dose and Figure 86 for all post dose timepoints) and VT-11134 (Figure 87 for 0 h to 72 h post dose and 
Figure 88 for all post dose timepoints) by Dose Group.


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•
Semi-log mean plots will be presented for VT-1598 (Figure 91 for 0 hours to 72 hours post dose and 
Figure 92 for all post dose timepoints) and for VT-11134 (Figure 93 for 0 hours to 72 hours post dose 
and Figure 94 for all post dose timepoints) by Dose Group.
•
Mean cumulative amount excreted into urine will be presented graphically by Dose Group in plots 
with error bars representing ± 1 SD around each sample collection time for both VT-1598 (Figure 89) 
and VT-11134 (Figure 90).
•
Mean concentration in plasma profiles by analyte will be presented graphically for each Dose Group 
separately in Figure 95 for the 40 mg and 80 mg Fasted Dose Groups, in Figure 96 for the 160 mg 
Fasted and Fed Dose Groups, and in Figure 97 for the 320 mg and 640 mg Fasted Dose Groups.
•
Mean of cumulative amounts excreted into urine by analyte will be presented graphically for each 
Dose Group separately in Figure 98 for the 40 mg and 80 mg Fasted Dose Groups, in Figure 99 for the 
160 mg Fasted and Fed Dose Groups, and in Figure 100 for the 320 mg and 640 mg Fasted Dose 
Groups.
10.2. 
Noncompartmental Analysis 
PK parameters from plasma PK data will be estimated through NCA using version 8.2 or higher of Phoenix 
WinNonlin®. Actual post dose time will be used for the estimation of plasma PK parameters instead of 
nominal time. In the case of imputed sample collection times, the imputed time will be included in NCA. PK 
parameters derived from urine concentration data will be calculated using a combination of Phoenix 
WinNonlin and SAS version 9.4 or above. Any outliers identified in the PK analysis will be discussed in the 
analysis report. Outliers will not be excluded from the PK analysis. 
Summary statistics of PK parameter estimates by Dose Group will be presented in tables. Summary statistics 
will include the mean, SD, min, max, CV and GM: 
•
Plasma PK parameters will be summarized and presented tabularly for all Dose Groups for VT-1598 
(Table 73) and VT-11134 (Table 80).
•
Detailed summary statistics of each plasma PK parameter will be presented tabularly for each Dose 
Group for VT-1598 (beginning at Table 74 and continuing through Table 79) and VT-11134
(beginning at Table 81 and continuing through Table 86).
•
Urine PK parameters will be summarized and presented tabularly for all Dose Groups for VT-1598 
(Table 87) and VT-11134 (Table 94).
•
Detailed summary statistics of each urine PK parameter will be presented tabularly for each Dose 
Group for VT-1598 (beginning at Table 88 and continuing through Table 93) and VT-11134
(beginning at Table 95 and continuing through Table 100).
The definition of CV is described below: 
For an independent identically distributed random sample {x1, x2,…, xn} from a log-normal distribution, let s2 
be the sample variance statistic of the natural log-transformed values of the sample. The CV will be defined 
as: 
CV = √exp(s2) −1 
Phoenix WinNonlin NCA will use the following settings to compute parameters from plasma PK data: 
•
Linear Up Log Down calculation method


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• Uniform weighting 
• Oral dosing 
• Lambda Z Acceptance Criteria 
o Rsq_adjusted > 0.90 
o Span > 3 half-lives 
o Includes at least 3 timepoints after Tmax 
If an insufficient number of subjects meet the Lambda Z Acceptance Criteria for computing plasma PK 
parameters, then relaxed Lambda Z Acceptance Criteria may be used and will be described in the CSR.  
Cmax  
Cmax is defined as the maximum drug or metabolite concentration observed in plasma over all PK sample 
concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin. If there is no 
measurable concentration in the subject’s PK profile, then Cmax will be missing for that subject. Cmax will be 
reported in units of ng/mL. 
Tmax  
Time of maximum concentration (Tmax) is defined as the time at which the Cmax occurs. It will be obtained 
from the Tmax parameter calculated by WinNonlin. If there is no measurable Cmax in the subject’s PK profile, 
then Tmax will be missing for that subject. Tmax will be reported in units of h. 
λz 
The terminal phase elimination rate constant (λz) is defined as the first-order rate constant describing the rate 
of decrease of drug or metabolite concentration in the terminal phase (defined as the terminal region of the PK 
curve where drug or metabolite concentration follows first-order elimination kinetics). λz will be computed as 
the slope of a terminal region consisting of > 3 successive points in the plot of log-transformed concentration 
data versus time. λz will be estimated using uniform weighting.  
Timepoints used in the estimation of λz will be initially selected using the WinNonlin automatic algorithm. 
Manually chosen timepoints may be used at the discretion of the PK analyst after examination of the 
automatically chosen points in the context of the semi-log profile to improve estimation of λz on a case-by-
case basis. The set of points chosen must contain only timepoints after Tmax, include at least 3 timepoints, and 
satisfy the Lambda Z Acceptance Criteria described above. Otherwise, the elimination rate constant and all 
derived parameters (apparent terminal elimination half-life [t1/2], AUC Extrapolated to Infinity [AUC0-inf], 
apparent Clearance [CL/F], and apparent volume of distribution during terminal phase [Vd/F]) will be treated 
as missing.  
This parameter will be obtained from the Lambda_z parameter calculated by WinNonlin. λz will be reported 
in units of 1/h.  
t1/2 
The t1/2 is defined as the time required for the drug or metabolite concentration to decrease by a factor of one-
half in the terminal phase. The t1/2 can be estimated as ln(2)/ λz. It will be obtained from the HL_Lambda_z 
parameter calculated by WinNonlin. Half-life will be reported in units of h.  


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AUC 
AUC0-last is defined as the area under the concentration-time curve from dosing (time 0) to the time of the last 
measured concentration. AUC0-last will be estimated using the Linear Up Log Down calculation method and 
obtained from the AUClast parameter calculated by WinNonlin. 
AUC0-inf is defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit 
as the end time becomes arbitrarily large. AUC0-inf can be calculated by adding AUC0-last to an extrapolated 
value equal to the last measured concentration greater than the LLOQ divided by λz: 
AUC0-inf = AUC0-last + Clast
 𝛌𝐳 
Where Clast is the last measured concentration > LLOQ. AUC0-inf will be obtained from the AUCINF_obs 
parameter calculated by WinNonlin®.  
%AUCex is defined as percentage of AUC0-inf obtained by extrapolation from time of the last measured 
concentration to infinity. %AUCex can be calculated by dividing AUC from time of the last measured 
concentration to infinity by AUC0-inf:  
%AUC𝑒𝑥= AUC0−inf −AUC0−last
AUC0−inf
, 
 
If %AUCex is >20%, the estimated AUC0-inf will be excluded from statistical summaries of PK parameter 
estimates and downstream calculations. %AUCex will be obtained from the AUC_%Extrap_obs parameter 
calculated by WinNonlin.  
All AUCs will be reported in units of ng*h/mL. 
CL/F 
Apparent oral clearance (CL/F) will be obtained from Dose/AUCinf. If %AUCex is >20%, the estimated CL/F 
value will be excluded from statistical summaries of parameter estimates and downstream calculations. CL/F 
will be obtained from the CL_F_obs parameter calculated by WinNonlin. Clearance will be reported in units 
of L/h.  
Vd/F 
Apparent volume of distribution (Vd/F) will be calculated as (CL/F)/λz. If %AUCex is >20%, the estimated 
Vd/F value will be excluded from statistical summaries of parameter estimates and downstream calculations. 
Vd/F will be obtained from Vz_F_obs calculated by WinNonlin. Volume will be reported in units of L.  
Aelast  
Aelast is defined as the cumulative amount of drug or metabolite excreted into urine up to the collection time 
of the last measurable concentration. Amount of drug or metabolite will be reported in units of mg. 
Ae%Dose 
Ae%Dose is defined as the percent of drug (VT-1598) excreted into urine up to the ending time of the last 
measurable concentration. Ae%Dose will be obtained from Aelast/Dose*100%. 


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CLR 
CLR is defined as the renal clearance of drug or metabolite and will be calculated as Aelast/AUC0-t1. Where 
AUC0-t1 is defined as AUC from dosing (time 0) to collection time (t1) based on the last collected 
concentration in urine (0 h to 72 h post dose). AUC0-t1 will be converted to mg*min/mL for calculations of 
CLR. CLR will be treated a missing if AUC0-t1 or Aelast is not estimable. Renal clearance of VT-1598 or VT-
11134 will be reported in units of mL/min.  
10.3. 
Statistical Analysis 
The PK Analysis Subset will be used for statistical analyses of plasma and urine PK parameters described 
above.  
10.3.1. 
Assessment of Dose Proportionality 
The presence of dose proportionality in plasma in terms of exposure parameters (Cmax, AUC0-last, and 
AUC0-inf) over the range of studied doses will be assessed among the Fasted Dose Groups using a power 
model approach with methods described by Smith et al. [5] The PK Analysis Subset will be used for this 
analysis.  
The power model for the specific case of AUC0-last may be specified with model parameters α and β to be 
estimated as: 
𝐴𝑈𝐶0−𝑙𝑎𝑠𝑡= 𝑒α × 𝑑𝑜𝑠𝑒β
Let ρ be the highest dose studied / lowest dose studied and let (L, U) represent the 90% CI for β̂. In the 
presence of dose proportionality,  ρβ̂/ρ = ρβ̂−1 = 1. Note that normality of β ̂is assumed, and this
assumption implies that ρβ̂−1 has an assumed log-normal distribution. Accordingly, dose proportionality
across the studied dose range is concluded using methodology analogous to that commonly used for an 
assessment of bioequivalence when:  
Θl = 0.8 ≤ ρ𝐿−1 < ρ𝑈−1  ≤ 1.25 = Θh.
Or, equivalently, 
1 + 
log 0.8
log ρ ≤L <  𝑈 ≤1 + 
log 1.25
log ρ . 
The analysis may be inconclusive if the CI (ρ𝐿−1, ρ𝑈−1) overlaps partially with the interval (0.80, 1.25) or if
the (ρ𝐿−1, ρ𝑈−1) contains the interval (0.80, 1.25).
If graphical evidence suggests dose proportionality may exist over a subset of the dose range, the above 
criteria of Smith et al [5]. may be applied to a subset of the data only containing values for subjects within a 
limited dose range. If lack of dose proportionality is evident for higher doses, other dose proportionality 
analyses using a subset of the full dose range studied may be explored. 
Dose proportionality assessments will be presented graphically and tabularly: 
•
Tabular results of statistics and parameters from the plasma dose proportionality power model will be 
presented for both VT-1598 and VT-11134 in Table 101.
•
Predicted values from a power model, including 90% pointwise prediction bands, will be overlaid on 
plots of the exposure parameter parameters (Cmax, AUC0-last, or AUC0-inf) versus dose. Pointwise 
prediction bands will be defined by lower and upper limits of 90% pointwise prediction intervals


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computed from the power model at each planned level dose level. Figures will be presented for all 
exposure parameters. For VT-1598, Cmax will be presented in Figure 101, AUC0-last in Figure 102, 
and AUC0-inf in Figure 103. For VT-11134, Cmax will be presented in Figure 104, AUC0-last in Figure 
105, AUC0-inf in Figure 106. 
10.3.2. 
Analysis of Change in Tmax between Fasted and Fed Dose Groups 
The difference in median Tmax values and the corresponding 90% CI for the difference between the 160 mg 
Fasted Dose Group and Fed Dose Group will be estimated using the PK Analysis Subset. An exact Wilcoxon 
signed-rank test will be conducted to compare Tmax between subjects who participated in both cohorts. This 
paired analysis will only be conducted if there are at least 3 individual subjects in the PK Analysis Population 
who are in Cohort 3 as well as Cohort 6. An exact Wilcoxon rank sum test will be used to compare the 
difference in median Tmax between all subjects in the 160 mg Fasted Dose Group to the 160 mg Fed Dose 
Group, regardless of whether the subject participated in both dosing periods. Continuity corrections will not 
be used for either test. Results from the paired and unpaired comparison of changes in Tmax will be presented 
in Table 102. 
10.3.3. 
Analysis of Exposure Parameter Ratios between Fasted and Fed Dose Groups 
Exposure parameters (Cmax, AUC0-last, and AUC0-inf), will be compared between the 160 mg Fasted and Fed 
Dose Groups using the PK Analysis Subset. The ratio of the GM of each parameter for the fed group 
compared to the GM of the same parameter in the corresponding fasted group will be estimated using a mixed 
effects model. Each exposure parameter will be estimated by fasting status with a random subject effect and a 
heterogeneous compound symmetry covariance structure. Because a random subject effect will be included, 
only one analysis will be conducted on all subjects in the 160 mg Fasted and 160 mg Fed Dose Groups for 
each exposure parameter, regardless of whether the subject participated in both dosing periods. In the event of 
nonconvergence of the model, first an unstructured covariance matrix will be specified. If the model still fails 
to converge the random subject effect will be removed from the model. 
Table 103 will display results comparing exposure parameters in both VT-1598 and VT-11134 between the 
160 mg Fasted and 160 mg Fed Dose Groups, including the ratio estimate and a 90% CI.  
Pseudo code to estimate the ratio of exposure parameters between the 160 mg Fasted and 160 mg Fed Dose 
Groups is presented below. Variables to be used in the model are also detailed below: 
•
FedCondition = indicator for dose received and fasting status; 160 mg Fed = 1, 160 mg Fasted = 2
•
ExposureParam_LN = log transformed values of exposure parameters for each subject.
proc mixed data=data; 
class Subject_ID FedCondition; 
model ExposureParam_LN= Subject_ID  FedCondition /DDFM=SATTERTH; 
random FedCondition /type=CSH sub= Subject_ID  G; 
repeated /grp= FedCondition  sub= Subject_ID; 
estimate 'Ratio of Fed to Fast' FedCondition  1 -1/CL alpha=0.1; 
run; 


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Where ExposureParam_LN is the natural log of the exposure parameter being modeled (Cmax, AUC0-last, and 
AUC0-inf) and FedCondition is a variable indicating the fed vs fasting condition. The estimate statement will 
give the mean of the natural log values of each exposure parameter and the associated 90% CIs on the log 
scale. Exponentiating the results of the estimate statement will give the GM and associated 90% CIs for each 
exposure parameter.  
The resulting estimate from the mixed effects model will give the difference in log transformed values of the 
mean for each exposure parameter and the associated 90% CI on the log scale. These values will be 
exponentiated in order to present the ratio of the GM of exposure parameters and corresponding CIs on the 
original scale. This model and subsequent exponential transformation will be repeated for each exposure 
parameter (Cmax, AUC0-last, and AUC0-inf). An absence of food effect will be indicated by the 90% CI being 
contained in the equivalence limits of 80-125 percent for Cmax, AUC0-last, and AUC0-inf, per FDA guidance on 
the assessment of food effect [7]. 


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11. 
IMMUNOGENICITY 
There are no immunogenicity endpoints in this trial.  


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12. 
OTHER ANALYSES 
Not applicable.  


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13. 
REPORTING CONVENTIONS 
P-values >0.001 and <0.999 will be reported to 3 decimal places; p-values less than 0.001 will be reported as 
“<0.001”; p-values greater than 0.999 will be reported as “>0.999”. The mean, median, SD, and any other 
statistics (other than quantiles), will be reported to one decimal place greater than the original data. Order 
statistics, such as the min and max values, will use the same number of decimal places as the original data. 
Proportions will be presented as 2 decimal places; values <0.01 will be presented as “<0.01”. Percentages will 
be reported to the nearest whole number; values <1% will be presented as “<1”. Estimated parameters not on 
the same scale as raw observations (e.g., regression coefficients) will be reported to 3 significant figures.  
For PK parameters, AUCs will be reported using 3 significant digits. t1/2, Tmax, CL/F, and Vd/F values will be 
reported using 2 significant digits. λz values will be reported to 3 significant digits. Cmax will be reported with 
the same number of significant digits as the measurement.  
Listings of individual subject data will include a Subject ID column. The subject identifiers assigned by site 
staff are replaced throughout this report with the Study Day Tabulation Model (SDTM) variable USUBJID to 
protect the confidentiality of those who volunteered to participate in this protocol. USUBJID has been created 
as a composite of the 3-letter EDC platform code followed by a numeric identifier assigned chronologically to 
enrolled subjects as well as Screening failures across all sites and protocols in the EDC platforms. Any data 
sharing activities will include the USUBJID and not the subject identifiers assigned at the study site.  
 


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14. 
TECHNICAL DETAILS 
SAS version 9.4 or above and R versions 3.2 or above will be used to generate tables, figures, and listings. PK 
parameters will be estimated through NCA using Phoenix® WinNonlin version 8.2 or later. 


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15. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES 
Only one subject from the fasted 160 mg cohort (Cohort 3) returned for the fed 160 mg cohort (Cohort 6). 
This impacts the planned analysis of change in Tmax between fasted and fed Dose Groups. Previously, an exact 
Wilcoxon-signed rank test had been proposed to compare subjects who had participated in both cohorts, 
however since fewer than 3 subjects were present in both cohorts, this analysis was not completed. Instead, 
only an exact Wilcoxon rank sum test was performed to compare the change in Tmax between fasted and fed 
Dose Groups. 


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16. 
REFERENCES 
1. ICH Harmonised Tripartite Guideline. Structure and Content of Clinical Study Reports E3. 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. 1995. Retrieved from: 
https://database.ich.org/sites/default/files/E3_Guideline.pdf 
2. ICH Harmonised Tripartite Guideline. General Considerations for Clinical Trials E8. International 
Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 
Human Use. 1997. Retrieved from: https://database.ich.org/sites/default/files/E8_Guideline.pdf 
3. ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9. International 
Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 
Human Use. 1998. Retrieved from: https://database.ich.org/sites/default/files/E9_Guideline.pdf 
4. Investigator’s Brochure. VT-1598. Edition No. 002. NQP 1598, Ltd. 20 April 2017. 
5. Smith, Brian P., et al. Confidence interval criteria for assessment of dose proportionality. 
Pharmaceutical Research 17.10 (2000): 1278-1283. 
6. Interim Pharmacokinetic Noncompartmental Statistical Analysis Plan v1.0 for DMID Protocol 17-
0087. Emmes Corporation; January 2021. 
7. A Phase 1, First-In-Human, Randomized, Double-Blind, Placebo Controlled, Single Dose-Escalation 
Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of VT-1598 in Healthy Adult 
Subjects v5.0 for DMID Protocol 17-0087. Emmes Corporation; June 2021. 
 


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17.
LISTING OF TABLES, FIGURES, AND LISTINGS
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. 


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APPENDICES 


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APPENDIX 1. TABLE MOCK-UPS 
LIST OF TABLES 
Table 1: 
Study Design ...............................................................................................................48 
Table 2: 
Schedule of Study Procedures ....................................................................................49 
Table 3: 
Clinical Adverse Event Toxicity Grading Scale .........................................................52 
Table 4: 
Clinical Laboratory Reference Ranges and Toxicity Grading Scales ........................53 
Table 5: 
Vital Signs Toxicity Grading Scale ............................................................................55 
Table 6: 
ECG Toxicity Grading Scale ......................................................................................56 
Table 7: 
Analysis Timepoints for Safety and PK Endpoints ....................................................57 
Table 8: 
Distribution of Protocol Deviations by Category, Deviation Type, and Dose 
Group ..........................................................................................................................59 
Table 9: 
Subject Disposition by Dose Group ...........................................................................61 
Table 10: Analysis Population Exclusions by Dose Group ........................................................62 
Table 11: Ineligibility Summary of Screen Failures ...................................................................63 
Table 12: Summary of Categorical Demographic and Baseline Characteristics by Dose 
Group ..........................................................................................................................66 
Table 13: Summary of Continuous Demographic and Baseline Characteristics by Dose 
Group ..........................................................................................................................67 
Table 14: Summary of Subjects with Pre-Existing Medical Conditions by MedDRA 
System Organ Class and Dose Group .........................................................................68 
Table 15: Number and Percentage of Subjects with Prior Medications by WHO Drug 
Classification and Dose Group ...................................................................................69 
Table 16: Number and Percentage of Subjects with Concurrent Medications by WHO 
Drug Classification and Dose Group ..........................................................................70 
Table 17: Overall Summary of Adverse Events by Dose Group ................................................71 
Table 18: Adverse Events Occurring in 5% of Subjects in Any Dose Group by 
MedDRA System Organ Class, Preferred Term, and Dose Group - Safety 
Population ...................................................................................................................72 
Table 19: Summary of Unsolicited Adverse Events by MedDRA System Organ Class 
and Preferred Term, Dose Number, and Dose Group ................................................73 
Table 20: Unsolicited Adverse Events by MedDRA System Organ Class and Preferred 
Term, Maximum Severity, Relationship, and Dose Group ........................................74 
Table 21: Listing of Serious Adverse Events .............................................................................75 
Table 22: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events ...............76 
Table 23: Listing of Abnormal Laboratory Results – Chemistry ...............................................78 


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Table 24: Listing of Abnormal Laboratory Results – Hematology ............................................79 
Table 25: Listing of Abnormal Laboratory Results - Coagulation .............................................80 
Table 26: Listing of Abnormal Laboratory Results - Urinalysis ................................................81 
Table 27: Chemistry Abnormal Results by Parameter, Dose Group, and Timepoint .................82 
Table 28: Chemistry Laboratory Toxicity Grade by Parameter, Dose Group, 
Timepoint, and Severity ..............................................................................................83 
Table 29: Chemistry Summary Statistics Change from Baseline by Parameter, Dose 
Group, and Timepoint .................................................................................................84 
Table 30: Hematology Abnormal Results by Parameter, Dose Group, and Timepoint .............85 
Table 31: Hematology Laboratory Toxicity Grade by Parameter, Dose Group, 
Timepoint, and Severity ..............................................................................................85 
Table 32: Hematology Summary Statistics Change from Baseline by Parameter, Dose 
Group, and Timepoint .................................................................................................85 
Table 33: Coagulation Abnormal Results by Parameter, Dose Group, and Timepoint ..............86 
Table 34: Coagulation Laboratory Toxicity Grade by Parameter, Dose Group, 
Timepoint, and Severity ..............................................................................................86 
Table 35: Coagulation Summary Statistics Change from Baseline by Parameter, Dose 
Group, and Timepoint .................................................................................................86 
Table 36: Urinalysis Abnormal Results by Parameter, Dose Group, and Timepoint .................87 
Table 37: Urinalysis Laboratory Toxicity Grade by Parameter, Dose Group, 
Timepoint, and Severity ..............................................................................................87 
Table 38: Urinalysis Summary Statistics Change from Baseline by Parameter, Dose 
Group, and Timepoint .................................................................................................87 
Table 39: Vital Sign Toxicity Grade by Parameter, Dose Group, Timepoint, and 
Severity .......................................................................................................................88 
Table 40: Vital Sign Change from Baseline by Parameter, Dose Group, and Timepoint ..........89 
Table 41: Summary of Post Dose ECG Change in Overall Interpretations from 
Baseline by Dose Group and Timepoint .....................................................................90 
Table 42: ECG Toxicity Grade by Parameter, Severity, Dose Group, and Timepoint ...............91 
Table 43: ECG Change from Baseline by Parameter, Severity, Dose Group, and 
Timepoint ....................................................................................................................92 
Table 44: Categorical Summary of QTcF by Dose Group and Timepoint .................................93 
Table 45: VT-1598 Concentrations in Plasma by Dose Group – 0 h to 14 h Post Dose ............94 
Table 46: VT-1598 Concentrations in Plasma by Dose Group – 24 h to 480 h Post 
Dose ............................................................................................................................95 


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Table 47: VT-1598 Concentrations in Plasma, SAD 40 mg Fasted Dose Group – 0 h to 
14 h Post Dose ............................................................................................................96 
Table 48: VT-1598 Concentrations in Plasma, SAD 40 mg Fasted Dose Group – 24 h 
to 480 h Post Dose ......................................................................................................97 
Table 49: VT-1598 Concentrations in Plasma, 80 mg Fasted Dose Group – 0 h to 14 h 
Post Dose ....................................................................................................................98 
Table 50: VT-1598 Concentrations in Plasma, 80 mg Fasted Dose Group – 24 h to 480 
h Post Dose .................................................................................................................98 
Table 51: VT-1598 Concentrations in Plasma, 160 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................98 
Table 52: VT-1598 Concentrations in Plasma, 160 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................98 
Table 53: VT-1598 Concentrations in Plasma, 160 mg Fed Dose Group – 0 h to 14 h 
Post Dose ....................................................................................................................98 
Table 54: VT-1598 Concentrations in Plasma, 160 mg Fed Dose Group – 24 h to 480 h 
Post Dose ....................................................................................................................98 
Table 55: VT-1598 Concentrations in Plasma, 320 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................98 
Table 56: VT-1598 Concentrations in Plasma, 320 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................98 
Table 57: VT-1598 Concentrations in Plasma, 640 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................98 
Table 58: VT-1598 Concentrations in Plasma, 640 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................99 
Table 59: VT-11134 Concentrations in Plasma by Dose Group – 0 h to 14 h Post Dose ..........99 
Table 60: VT-11134 Concentrations in Plasma by Dose Group – 24 h to 480 h Post 
Dose ............................................................................................................................99 
Table 61: VT-11134 Concentrations in Plasma, 40 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................99 
Table 62: VT-11134 Concentrations in Plasma, 40 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................99 
Table 63: VT-11134 Concentrations in Plasma, 80 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................99 
Table 64: VT-11134 Concentrations in Plasma, 80 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................99 
Table 65: VT-11134 Concentrations in Plasma, 160 mg Fasted Dose Group – 0 h to 14 
h Post Dose .................................................................................................................99 


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Table 66: VT-11134 Concentrations in Plasma, 160 mg Fasted Dose Group – 24 h to 
480 h Post Dose ..........................................................................................................99 
Table 67: VT-11134 Concentrations in Plasma, 160 mg Fed Dose Group – 0 h to 14 h 
Post Dose ..................................................................................................................100 
Table 68: VT-11134 Concentrations in Plasma, 160 mg Fed Dose Group – 24 h to 480 
h Post Dose ...............................................................................................................100 
Table 69: VT-11134 Concentrations in Plasma, 320 mg Fasted Dose Group – 0 h to 14 
h Post Dose ...............................................................................................................100 
Table 70: VT-11134 Concentrations in Plasma, 320 mg Fasted Dose Group – 24 h to 
480 h Post Dose ........................................................................................................100 
Table 71: VT-11134 Concentrations in Plasma, 640 mg Fasted Dose Group – 0 h to 14 
h Post Dose ...............................................................................................................100 
Table 72: VT-11134 Concentrations in Plasma, 640 mg Fasted Dose Group – 24 h to 
480 h Post Dose ........................................................................................................100 
Table 73: Summary Statistics for VT-1598 PK Parameters in Plasma by Dose Group ...........101 
Table 74: Summary Statistics for VT-1598 PK Parameters in Plasma, 40 mg Fasted 
Dose Group ...............................................................................................................102 
Table 75: Summary Statistics for VT-1598 PK Parameters in Plasma, 80 mg Fasted 
Dose Group ...............................................................................................................103 
Table 76: Summary Statistics for VT-1598 PK Parameters in Plasma, 160 mg Fasted 
Dose Group ...............................................................................................................103 
Table 77: Summary Statistics for VT-1598 PK Parameters in Plasma, 160 mg Fed 
Dose Group ...............................................................................................................103 
Table 78: Summary Statistics for VT-1598 PK Parameters in Plasma, 320 mg Fasted 
Dose Group ...............................................................................................................103 
Table 79: Summary Statistics for VT-1598 PK Parameters in Plasma, 640 mg Fasted 
Dose Group ...............................................................................................................103 
Table 80: Summary Statistics for VT-11134 PK Parameters in Plasma by Dose Group .........103 
Table 81: Summary Statistics for VT-11134 PK Parameters in Plasma, 40 mg Fasted 
Dose Group ...............................................................................................................103 
Table 82: Summary Statistics for VT-11134 PK Parameters in Plasma, 80 mg Fasted 
Dose Group ...............................................................................................................103 
Table 83: Summary Statistics for VT-11134 PK Parameters in Plasma, 160 mg Fasted 
Dose Group ...............................................................................................................103 
Table 84: Summary Statistics for VT-11134 PK Parameters in Plasma, 160 mg Fed 
Dose Group ...............................................................................................................104 
Table 85: Summary Statistics for VT-11134 PK Parameters in Plasma, 320 mg Fasted 
Dose Group ...............................................................................................................104 


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Table 86: Summary Statistics for VT-11134 PK Parameters in Plasma, 640 mg Fasted 
Dose Group ...............................................................................................................104 
Table 87: Summary Statistics for VT-1598 PK Parameters in Urine by Dose Group .............105 
Table 88: Summary Statistics for VT-1598 PK Parameters in Urine, 40 mg Fasted 
Dose Group ...............................................................................................................106 
Table 89: Summary Statistics for VT-1598 PK Parameters in Urine, 80 mg Fasted 
Dose Group ...............................................................................................................107 
Table 90: Summary Statistics for VT-1598 PK Parameters in Urine, 160 mg Fasted 
Dose Group ...............................................................................................................107 
Table 91: Summary Statistics for VT-1598 PK Parameters in Urine, 160 mg Fed Dose 
Group ........................................................................................................................107 
Table 92: Summary Statistics for VT-1598 PK Parameters in Urine, 320 mg Fasted 
Dose Group ...............................................................................................................107 
Table 93: Summary Statistics for VT-1598 PK Parameters in Urine, 640 mg Fasted 
Dose Group ...............................................................................................................107 
Table 94: Summary Statistics for VT-11134 PK Parameters in Urine by Dose Group ...........108 
Table 95: Summary Statistics for VT-11134 PK Parameters in Urine, 40 mg Fasted 
Dose Group ...............................................................................................................109 
Table 96: Summary Statistics for VT-11134 PK Parameters in Urine, 80 mg Fasted 
Dose Group ...............................................................................................................110 
Table 97: Summary Statistics for VT-11134 PK Parameters in Urine, 160 mg Fasted 
Dose Group ...............................................................................................................110 
Table 98: Summary Statistics for VT-11134 PK Parameters in Urine, 160 mg Fed 
Dose Group ...............................................................................................................110 
Table 99: Summary Statistics for VT-11134 PK Parameters in Urine, 320 mg Fasted 
Dose Group ...............................................................................................................110 
Table 100: Summary Statistics for VT-11134 PK Parameters in Urine, 640 mg Fasted 
Dose Group ...............................................................................................................110 
Table 101: Assessment of Dose Proportionality Among Fasted Dose Groups ..........................111 
Table 102: Comparison of Tmax between Fasted and Fed 160 mg Dose Groups ........................112 
Table 103: Comparison of Plasma PK Exposure Parameters between Fasted and Fed 
160 mg Dose Groups – VT-1598..............................................................................113 


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9.1 
Overall Study Design and Plan Description 
Table 1: 
Study Design 
Cohort 
Dosea 
(mg) 
Fasting 
Status 
VT-1598 
Placebo 
Cohort Comments 
Number of 
Subjectsb 
Study 
Product 
Number of 
Subjectsb 
Study 
Product 
1 
40 
Fasted 
6 
Single 40 
mg VT-1598 
tablet 
2 
Single 40 mg 
matching 
Placebo  
Safety data for Cohort 1 subjects through Day 7 
will be confirmed by reviewing objective pre-
defined criteria before continuing to Cohort 2. 
2 
80 
Fasted 
6 
Two 40 mg 
VT-1598 
tablets 
2 
Two 40 mg 
matching 
Placebo  
Safety data for Cohort 2 subjects through Day 7 
will be confirmed by reviewing objective pre-
defined criteria before continuing to Cohort 3. 
3 
160 
Fasted 
6 
Four 40 mg 
VT-1598 
tablets 
2 
Four 40 mg 
matching 
Placebo  
Safety data for Cohort 3 subjects through Day 7 
will be confirmed by reviewing objective pre-
defined criteria before continuing to Cohorts 4 
and 6. Interim analysis of PK data (Cohorts 1-
3) c. 
4 
320 
Fasted 
6 
Four 80 mg 
VT-1598 
tablets 
2 
Four 80 mg 
matching 
Placebo  
Cumulative safety data for all subjects in 
Cohorts 1-4 through Day 21 will be reviewed 
by the SMC for recommendation/confirmation 
of dosing before continuing to Cohort 5. 
5 
640 
Fasted 
6 
Eight 80 mg 
VT-1598 
tablets 
2 
Eight 80 mg 
matching 
Placebo  
 
6 
160 
Fed 
6 
Four 40 mg 
VT-1598 
tablets 
2 
Four 40 mg 
matching 
Placebo  
Cohort 6 is comprised of the same subjects as 
Cohort 3.d These subjects will receive the same 
study product in Cohort 6 as Cohort 3, 
following a high-fat, high-calorie meal. Cohort 
6 may start enrolling prior to convening the 
SMC meeting and prior to the start of Cohort 5. 
a Dose refers to the free base equivalent of the drug. 
b Within each fasted cohort, two sentinel subjects will be admitted initially, and the randomization scheme will be designed to ensure that one 
subject will receive VT-1598 and the other will receive placebo. All sentinel subject safety data through Day 3 is reviewed by PI prior to 
dosing the remainder of the cohort.  
c PK data only. Enrollment for Cohort 4 will not stop for the PK interim analysis.   
d The Cohort 6 replacement subjects will receive the same treatment as assigned to the Cohort 3 subject they are replacing. 
 


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9.5.1 Pharmacokinetics and Safety Measurements Assessed and Flow Chart 
Table 2: 
Schedule of Study Procedures 
Activity 
Screening 
Baseline 
Inpatient (Treatment) Period 
Follow-up Period 
Unscheduled 
Study Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Days 2 & 3 
Day 4 
Day 7 (±1 
day) 
Day 14 (± 1 
day) 
Day 21/ End 
of Studys (±2 
days) 
Informed Consent 
X 
Demographics 
X 
Inclusion/Exclusion Criteria 
X 
X 
Height, Weight, BMI 
X 
Xa 
Medical Historyb 
X 
Xc 
Xc 
Xc 
Xc 
Physical Examination 
Xd 
Xe 
Xe 
Xe 
Xe 
Xe 
Vital Signsf 
Xf
Xf
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
ECGg 
Xg 
Xg 
Xg 
Xg 
Xg 
Clinical Laboratory Testsh 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Testi 
X 
X 
X 
FSHj 
X 
Drug Screenk 
X 
X 
Immunology Screenl 
X 
PK Blood Samplesm 
Xm
Xm 
Xm 
Xm 
Xm 
Xm 
Xm 
PK Urine Samplesn 
Xn 
Xn 
Xn 
Future Use Specimen Collection 
X 
Prior/Concomitant 
Medications/Treatments 
X 
X 
Xo
X 
X 
X 
X 
X 
X 


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Activity 
Screening 
Baseline 
Inpatient (Treatment) Period 
Follow-up Period 
Unscheduled 
Study Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Days 2 & 3 
Day 4 
Day 7 (±1 
day) 
Day 14 (± 1 
day) 
Day 21/ End 
of Studys (±2 
days) 
Review/confirm adherence to 
dietary restrictions/birth control 
methodsP 
X 
X 
X 
X 
X 
X 
Admit to CRU 
X 
Discharge from CRU 
X 
Receive study productq,r 
X 
Collect and Record AEs 
X 
X 
X 
X 
X 
X 
X 
*Cohort 6 may enroll prior to the SMC meeting or prior to the start of Cohort 5 (but no less than 60 days after completion of Cohort 3).
Abbreviations: AE: adverse event; BMI: body mass index; ECG: electrocardiogram; EW: early withdrawal; FSH: follicle-stimulating hormone; HIV-1: Human Immunodeficiency Virus-1; HIV-2:
Human Immunodeficiency Virus-2; HBsAg: Hepatitis B surface antigen; Anti-HCV: anti-Hepatitis C virus; IMP: investigational medicinal product; PK, pharmacokinetics.  
a Weight and BMI only. 
b Including alcohol and tobacco use history. 
c Update medical history as appropriate from previous visit. 
d Complete physical examination (general appearance; head, eyes, ears, nose, and throat; neck; chest and lungs; cardiovascular system, abdomen, musculoskeletal system, lymph nodes, extremities/skin, 
and neurological system). 
e Targeted physical examination (general appearance, heart, lungs, skin, and abdomen). On Day 4, targeted PE will be performed at 72 hours (±30 min). 
f Vital signs (hear rate, blood pressure, temperature, and respiratory rate) at Screening, Day -1, pre-dose on Day 1 and approximately 1,2,4,8,24 (Day 2), 48 (Day 3), 72 (Day 4), 144 (Day 7 outpatient 
visit), 312 (Day 14 outpatient visit) and 480 (Day 21 outpatient visit) hours after dosing. The pre-dose Day 1 vital signs measurements should be taken within 60 minutes of dosing. Day 1 post dose 
vital sign measurements should be taken ± 10 minutes of the nominal timepoint. All other vital sign measurements during the inpatient stay should be taken within ± 30 minutes of the nominal 
timepoint. For outpatient visits, vital sign measurements should be taken within the visit window. All vital signs are taken after a subject is at rest for at least 5 minutes.  
g ECGs will be performed at Screening; pre-dose taken within 60 minutes of dosing and post dose, taken 4 hours after dosing on Day 1; at 72 hours (± 30 minutes) prior to discharge from the CRU on 
Day 4 (±12 min), and on Day 21. All ECG readings are triplicate readings, at least 1 minute apart within a 15-minute period and are taken after at least 5 minutes in the supine position. For the Day 21 
outpatient visit, the ECG should be taken within the visit window.  
h Clinical laboratory tests include: clinical chemistry panel (albumin, glucose, blood urea nitrogen or urea potassium, calcium, sodium, chloride, total protein, creatinine, triglycerides, total cholesterol, 
low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total carbon dioxide, creatine phosphokinase, phosphorus, alkaline phosphatase, aspartate aminotransferase, alanine 
aminotransferase, total bilirubin, direct bilirubin, magnesium, gamma-glutamyl transferase (GGT) and serum cortisol), hematology (red blood cell count, total and white differential white blood cell 
count, hemoglobin, hematocrit, and platelet count), coagulation parameters (activated partial thromboplastin time, prothrombin time, and international normalized ratio), and urinalysis (leukocyte 
esterase, blood, pH, and specific gravity [microscopic tests to be completed if dipstick urinalysis is abnormal]). Subjects must fast at least 8 hours before blood collection for the clinical chemistry 
panel. Cortisol must be fasting and drawn before 10 a.m. 
i Serum pregnancy test for women of childbearing potential at Screening, Day -1, and Day 21 (Final Study Visit). 
j Follicle-stimulating hormone on all post-menopausal women at Screening.  


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Activity 
Screening 
Baseline 
Inpatient (Treatment) Period 
Follow-up Period 
Unscheduled 
Study Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Days 2 & 3 
Day 4 
Day 7 (±1 
day) 
Day 14 (± 1 
day) 
Day 21/ End 
of Studys (±2 
days) 
k Urine drug test at Screening and on Day -1 to include cotinine, opiates, cocaine, cannabinoids, phencyclidine, benzodiazepines, barbiturates, amphetamines, and cotinine. Alcohol screen is performed 
by urine test. 
l Immunology screen to include test for the detection of antibodies to HIV-1 and HIV-2, HBsAg, and antibodies to HCV.
m PK blood samples will be collected on the following schedule following study product administration on Day 1: pre-dose, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72, 144 (Day 7
outpatient visit), 312 (Day 13 outpatient visit) and 480 (Day 21 outpatient visit) hours post dose. The pre-dose Day 1 PK blood sample should be taken within 60 minutes of before dosing for the 
fasted cohorts and within 30 minutes of the start of the pre-dose meal for the fed cohort; the Day 1 0.5-hour post dose blood sample should be taken within ± 5 minutes of the nominal timepoint. 
Remaining post dose Day 1 PK blood sample should be taken within ± 10 minutes of the nominal timepoint. An additional 6 mL blood for future use is collected at 6 hours (+/10 minutes) post dose. 
day 2, 3, and 4 PK blood samples should be taken within ± 30 minutes of the nominal timepoint. For outpatient visits, PK blood samples should be taken within the visit window. PK blood samples 
take precedence; however vital signs and ECGs should be completed before the blood draw, when possible. 
n PK urine samples will be collected in the following intervals, following study product administration on Day 1: -6 to 0 hours before dose, and 0-6, 6-12, 12-24, 24-36, 36-48, 48-60-, and 60-72-hours 
post dose. 
o A review for concomitant medication will be performed before and after dosing on Day 1.
p Screening: review birth control methods, permitted/non-permitted medications, non-medications, dietary and activity restrictions; Day -1; confirm that subject adhered to dietary restrictions (no
food/beverage containing alcohol for previous 72 hours or caffeine for the previous 24 hours; no grapefruit, no grapefruit juice, or juices containing grapefruit, or Seville oranges for the previous 7 
days); Days 7 and 14 - confirm that the subject adhered to post-discharge dietary restrictions (no consumption of grapefruit, or juices containing grapefruit or Seville oranges, no alcohol consumption) 
until after the visit to the CRU on Day 14; Review post-discharge instructions (including birth control methods, permitted/non-permitted medications, non-medications, dietary and activity 
restrictions). 
q Cohorts 1-5 will receive study product when fasted and subjects will remain fasted for at least 4 hours post dose; Cohort 6 will receive study product following a high-fat, high-calorie meal, which is 
consumed within 30 minutes and dosing is administered at 30 minutes after the start of the meal.  
r For the nominal dose escalations, the study product will be administered in a fasted state and the subjects will remain fasted for 4 hours post dose. Cohort 6 will be dosed with 160 mg of study product 
after ingestion of a high-fat, high-calorie meal. 
s For unscheduled visits, Safety assessments including updated history and the following onsite evaluations will be obtained: AE, PE, and any other study procedures deemed necessary by the PI. Early 
termination assessments will be the same day as the Day 21 procedures. 


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Table 3: 
Clinical Adverse Event Toxicity Grading Scale 
System 
Toxicity  
Mild  
(Grade 1) 
Moderate 
(Grade 2)  
Severe 
(Grade 3) 
Gastrointestinal 
Nausea/vomiting 
No to mild interference 
with activity or 1 to 2 
episodes/24 hours 
Moderate interference 
with activity or >2 
episodes/24 hours 
Prevents daily activity, 
requires outpatient IV 
hydration 
  
Diarrhea 
2 - 4 loose stools or 
<400 gm/24 hours 
5-6 stools or 400 – 
800gm/24 hours 
7 or more watery stools 
or >800gms/24 hours or 
requires outpatient IV 
hydration 
Systemic Reactions 
Headache 
No interference with 
activity 
Repeated use of non-
narcotic pain reliever > 
24 hours or some 
interference with 
activity 
Significant; any use of 
narcotic pain reliever or 
prevents daily activity 
  
Fatigue 
No interference with 
activity 
Some interference with 
activity 
Significant; prevents 
daily activity 
Other Conditions 
Illness or clinical AE (as defined 
according to applicable 
regulations) 
No interference with 
activity 
Some interference with 
activity, not requiring 
medical intervention 
Prevents daily activity 
and requires medical 
intervention 
 


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Table 4: 
Clinical Laboratory Reference Ranges and Toxicity Grading Scales 
Parametera 
Direction 
Mild  
(Grade 1) 
Moderate 
(Grade 2)  
Severe 
(Grade 3) 
Sodium (hyponatremia) - mEq/L 
Decrease 
131-132 
129-130 
<129 
Sodium (hypernatremia) - mEq/L 
Increase 
144-145 
146-147 
>147 
Potassium (hypokalemia) - mEq/L 
Decrease 
3.2-3.4 
3.0 – 3.1 
<3.0 
Potassium (hyperkalemia) - mEq/L 
Increase 
5.2 – 5.4 
5.5 – 5.6 
>5.6 
Phosphorus - mg/dL 
Decrease 
2.3 – 2.4 
2.1 – 2.2 
≤2.0 
Phosphorous - mg/dL 
Increase 
N/A 
N/A 
N/A 
Magnesium - mg/dL 
Decrease 
1.3-1.5 
1.1-1.2 
<1.1 
Gamma- Glutamyl Transferase (GGT) (Male) - U/L 
N/A 
N/A 
N/A 
N/A 
Gamma- Glutamyl Transferase (GGT) (Female) - U/L 
N/A 
N/A 
N/A 
N/A 
Glucose (hypoglycemia) - mg/dL 
Decrease 
65 – 69 
55 – 64 
<55 
Glucose (hyperglycemia) (Fasting) - mg/dL 
Increase 
106 – 125 
126 – 200 
>200 
Blood Urea Nitrogen - mg/dL 
Increase 
21-26 
27 – 31 
> 31 
Creatinine (Male) - mg/dL 
Increase 
1.3 – 2.0 
2.1-2.3 
>2.3 
Creatinine (Female) - mg/dL 
Increase 
1.0 – 1.7 
1.8 – 2.0 
>2.0 
Calcium (hypocalcemia) - mg/dL 
Decrease 
8.0-8.7 
7.5 – 7.9 
<7.5 
Calcium (hypercalcemia) - mg/dL 
Increase 
10.4-10.8 
10.9-11.4 
>11.4 
Chloride - mEq/L 
N/A 
N/A 
N/A 
N/A 
CPKt (Male) - U/L 
Increase 
338.8-462 
462.1-924 
> 924.1 
CPKt (Female) - U/L 
Increase 
211.2-288 
288.1-576 
> 576.1 
A.M. Cortisol (serum, drawn prior to 10 a.m.) - ug/dL 
Decrease 
3.60-3.96 
3.00-3.59 
< 3.00 
Albumin (hypoalbuminemia) - g/dL 
Decrease 
2.8 – 3.4 
2.5 – 2.7 
< 2.5 
AST (Males) - U/L 
Increase 
44-100 
100.1-200 
> 200 
AST (Females) - U/L 
Increase 
35.2-80.0 
80.1-160.0 
> 160.0 
ALT (Males) - U/L 
Increase 
45.1-102.5 
102.51-205.0 
> 205.0 
ALT (Females) - U/L 
Increase 
36.3-82.5 
82.51-165.0 
> 165.0 
Total Bilirubin (serum) - mg/dL 
Increase 
1.32-1.50 
1.60-1.80 
> 1.80 
Direct Bilirubin - mg/dL 
Increase 
0.22-0.25 
0.26-0.30 
> 0.30 
Indirect Bilirubin - mg/dL 
Increase 
1.31-1.49 
1.491-1.79 
>1.79 
Amylase - U/L 
Increase 
162.8 -222.0 
222.1-296 
>296 
Lipase - U/L 
Increase 
73.7-100.5 
100.6-134 
>134 
Hemoglobin (Male) - g/dL 
Decrease 
11.2 - 12.2 
10.0 – 11.1 
<10.0 
Hemoglobin (Female) - g/dL 
Decrease 
9.8 - 10.8 
8.5 - 9.7 
<8.5 
WBC - cell/mm3 
Increase 
10,001– 15,000 
15,001 – 20,000 
> 20,000 
WBC (African American Males) - cell/mm3 
Increase 
9,001 – 14, 000 
14,001 – 19, 000 
>19,000 


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Parametera 
Direction 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC (African American Females) - cell/mm3 
Increase 
11,001 – 15,000 
15,001 – 20,000 
>20,000
WBC - cell/mm3 
Decrease 
2,500– 3,999 
1,500 – 2,499 
< 1,500 
WBC (African American Males) - cell/mm3 
Decrease 
2,200 – 2,499 
1,200 – 2,199 
<1,200 
WBC (African American Females) - cell/mm3 
Decrease 
2,200 – 2,499 
1,500 – 2,199 
<1,500 
Neutrophils - cell/mm3 
Decrease 
1,300 – <1,699 
1,000 – 1,299 
< 1,000 
Neutrophils (African American Males) - cell/mm3 
Decrease 
1,000 – 1,299 
800 - 999 
<800 
Neutrophils (African American Females) - cell/mm3 
Decrease 
1,100 – 1,299 
1,000 – 1,099 
<1,000 
Platelets - cell/mm3 
Decrease 
120,000 – <150,000 
100,000 – 119,999 
<100,000 
Prothrombin time - seconds 
Increase 
11.6 – 12.6 
12.7 – 13.7 
>13.7
Prothrombin INR 
Increase 
1.2-1.4 
1.5-1.9 
2.0 or higher 
PTT (partial thromboplastin time) - seconds 
Increase 
30.1 – 36.8 
36.9 – 43.6 
>43.6
Total Protein - g/dL 
Decrease 
5.5 - 5.9 
5.0 - 5.4 
<5.0 
Alkaline phosphatase (Male) - IU/L 
Increase 
131-260
264-390
> 390.1
Alkaline phosphatase (Female) - IU/L 
Increase 
106-210
211-315
> 315.1
Hematocrit (Male) - % 
Decrease 
33.0 -36.1 
29.8 - 32.9 
< 29.8 
Hematocrit (Female) - % 
Decrease 
29.5 - 32.6 
26.0 – 29.4 
< 26.0 
RBC (Male) - 106/uL 
Decrease 
3.9 - 4.1 
3.4 - 3.8 
< 3.4 
RBC (Female) - 106/uL 
Decrease 
3.5 - 3.7 
3.0 - 3.4 
< 3.0 
Lymphocytes - cell/mm3 
Decrease 
600- 799
500 – 599 
< 500 
Monocytes - cell/mm3 
Increase 
1001-2000 
2001-3000 
>3000
Eosinophils - cell/mm3 
Increase 
871 - 950 
951 - 1700 
>1700
Basophils - cell/mm3 
Increase 
101 - 300 
301 - 800 
> 800
High Density Lipoproteins (HDL) (Male) - mg/dL 
N/A 
N/A 
N/A 
N/A 
High Density Lipoproteins (HDL) (Female) - mg/dL 
N/A 
N/A 
N/A 
N/A 
Total Carbon Dioxide - mEq/L 
N/A 
N/A 
N/A 
N/A 
Total Cholesterol - mg/dL 
N/A 
N/A 
N/A 
N/A 
Low Density Lipoprotein Cholesterol, Direct - mg/dL 
N/A 
N/A 
N/A 
N/A 
Triglycerides - mg/dL 
N/A 
N/A 
N/A 
N/A 
Protein* 
Increase 
1+ 
2+ 
>2+
Glucose* 
Increase 
1+ 
2+ 
>2+
Blood (microscopic) - red blood cells per high power field - 
rbc/hpf* ° 
Increase 
3-10
11-50 
>50 and/or gross
blood 
a Laboratory tests without toxicity grading defined in the protocol have N/A in this table for grading ranges. 
*Abnormal laboratory values, performed as part of hematology, chemistry panel, or urinalysis but not listed in Table 4, VT-1598
TOXICITYGRADING CRITERIA FOR NORMAL HUMAN SUBJECTS, will be evaluated by the study clinicians, recorded in the source
document and, if clinically significant, considered AEs and graded according to the criterion described in version 5.0 of the study Protocol
Section 8.1.
° Hematuria during active menses is considered not clinically significant.


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Table 5: 
Vital Signs Toxicity Grading Scale 
Parameter 
Direction 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Fever (°C) 
Increase 
38.0-38.4 
38.5-38.9 
39.0-40 
Fever (°F) 
Increase 
100.4-101.1 
101.2-102.0 
102.1-104 
Tachycardia (bpm) 
Increase 
101-115
116-130
>130
Bradycardia (bpm), if baseline > 60 
Decrease 
50-54 
45-49 
<45 
Bradycardia (bpm), if baseline ≤ 60 
Decrease 
45-50 
40-44 
<40 
Hypertension (systolic) (mmHg) 
Increase 
141-150
151-155
>155
Hypotension (systolic) (mmHg) 
Decrease 
85-89 
80-84 
<80 
Hypertension (diastolic) (mmHg) 
Increase 
91-95 
96-100 
>100
Respiratory Rate (breaths/minute) 
Increase 
17-20 
21-25 
>25


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Table 6: 
ECG Toxicity Grading Scale 
Parameter 
Direction 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3) 
QTcF (ms) 
Increase 
> 30 but ≤ 60 above baseline 
> 60 above baseline to ≤ 500 
>500 
 
 


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Table 7: 
Analysis Timepoints for Safety and PK Endpoints 
Parameter 
Analysis Timepoint 
Abbreviated Label 
Endpoint 
CHEM, HEM, COAG, UA 
VS 
ECG 
Screening 
N/A 
CHEM, HEM, COAG, UA, VS, ECG 
Admission (Baseline)/ Admission 
d-1 
CHEM, HEM, COAG, UA/ VS, ECG 
Day 1, Pre-Dose (Baseline) 
0 h 
VS, ECG 
Maximum Severity Post baseline 
N/A 
CHEM, HEM, COAG, UA, VS, ECG 
Day 1, 1 h Post Dose 
1 h 
VS 
Day 1, 2 h Post Dose 
2 h 
VS 
Day 1, 4 h Post Dose 
4 h 
VS 
Day 1, 8 h Post Dose 
8 h 
VS 
Day 2 
d2 
VS 
Day 3 
d3 
VS 
Day 4  
d4 
CHEM, HEM, COAG, UA, VS, ECG 
Day 7  
d7 
CHEM, HEM, COAG, UA, VS 
Day 14 
d14 
CHEM, HEM, COAG, UA, VS 
Day 21 
d21 
CHEM, HEM, COAG, UA, VS, ECG 
PK 
Day 1, Pre-Dose 
0 h 
Plasma 
Day 1, Pre-Dose 
-6-0 h 
Urine 
Day 1, 0.5 h Post Dose 
0.5 h  
Plasma 
Day 1, 1 h Post Dose 
1 h 
Plasma 
Day 1, 1.5 h Post Dose 
1.5 h 
Plasma 
Day 1, 2 h Post Dose 
2 h  
Plasma 
Day 1, 3 h Post Dose 
3 h 
Plasma 
Day 1, 4 h Post Dose 
4 h 
Plasma 
Day 1, 6 h Post Dose 
6 h  
Plasma 
Day 1, 0-6 h Post Dose 
0-6 h 
Urine 
Day 1, 8 h Post Dose 
8 h 
Plasma 
Day 1, 10 h Post Dose 
10 h  
Plasma 
Day 1, 12 h Post Dose 
12 h 
Plasma 
Day 1, 6-12 h Post Dose 
6-12 h 
Urine 
Day 1, 14 h Post Dose 
14 h 
Plasma 
Day 2, 24 h Post Dose 
24 h 
Plasma 
Day 1, 12-24 h Post Dose 
12-24 h 
Urine 
Day 2, 36 h Post Dose 
36 h 
Plasma 
Day 2, 24-36 h Post Dose 
24-36 h 
Urine 
Day 3, 48 h Post Dose 
48 h 
Plasma 


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Parameter 
Analysis Timepoint 
Abbreviated Label 
Endpoint 
Day 2, 36-48 h Post Dose 
36-48 h 
Urine 
Day 3, 60 h Post Dose 
60 h 
Plasma 
Day 4, 72 h Post Dose 
72 h 
Plasma 
Day 3, 60-72 h Post Dose 
60-72 h 
Urine 
Day 7, 144 h Post Dose 
144 h 
Plasma 
Day 14, 312 h Post Dose 
312 h 
Plasma 
Day 21, 480 h Post Dose 
480 h 
Plasma 


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10.2 
Protocol Deviations 
Table 8: 
Distribution of Protocol Deviations by Category, Deviation Type, and Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same 
subjects in Cohort 3 who continued on to Cohort 6 separately.] 
Category 
Deviation Type 
Number of Subjects (Number of Deviations) 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
All 
Subjects 
(N=X) 
Eligibility/Enrollment 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Did not meet inclusion criterion 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Met exclusion criterion 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
ICF not signed prior to study procedures 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Treatment Administration Schedule Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Out of window visit 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Missed visit/visit not conducted 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Missed treatment administration 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Delayed treatment administration 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Follow-Up Visit Schedule 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Out of window visit 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Missed visit/visit not conducted 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Protocol Procedure/Assessment 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Incorrect version of ICF signed 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Blood not collected 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 


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Category 
Deviation Type 
Number of Subjects (Number of Deviations) 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
All 
Subjects 
(N=X) 
 
Urine not collected 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other specimen not collected 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Too few aliquots obtained 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Specimen result not obtained 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Required procedure not conducted 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Required procedure done incorrectly 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Study product temperature excursion 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Specimen temperature excursion 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Required specimen collected out of window 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Required procedure done out of window 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Treatment Administration 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Required procedure done incorrectly 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Study product temperature excursion 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Blinding Policy/Procedure 
Any type 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Treatment unblinded 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Other 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: N=The number of subjects enrolled/randomized. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns.   
 
 


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14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects 
Table 9: 
Subject Disposition by Dose Group 
[Implementation Note: N for the Placebo column will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects column will count the 
same subjects in Cohort 3 who continued on to Cohort 6 separately. 
The “Participated in Fast (Cohort 3) and Fed (Cohort 6) Cohorts” is the number of Cohort 3 subjects in each Dose Group who continued to Cohort 6. It 
will be “-“ for the Dose Groups to which it does not apply: 40 mg Fasted, 80 mg Fasted, 160 mg Fed, 320 mg Fasted, and 640 mg Fasted] 
Subject Disposition 
40 mg Fasted 
(N=X) 
80 mg Fasted 
(N=X) 
160 mg Fasted 
(N=X) 
160 mg Fed 
(N=X) 
320 mg Fasted 
(N=X) 
640 mg Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Screened 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
xx 
Enrolled/Randomized 
x (100) 
x (100) 
x (100) 
x (100) 
x (100) 
x (100) 
x (100) 
x (100) 
Received Study Product 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Completed all PK Blood Draws 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Completed all PK Urine Samples 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Completed Final Study Visit (Study Day 21) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Participated in Fast (Cohort 3) and Fed 
(Cohort 6) Cohorts 
- 
- 
x (x) 
- 
- 
- 
x (x) 
x (x) 
Early Termination 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: N=Number of subjects enrolled/randomized. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns. 


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Table 10: 
Analysis Population Exclusions by Dose Group 
[Implementation Notes: Although subjects may meet multiple criteria for exclusion, each subject randomized to VT-1598 or Placebo in Cohorts 1,2,4, or 
5 will only be counted under one reason for exclusion in this table. Cohort 3 subjects randomized to Placebo who continued on to Cohort 6 will be 
counted once per reason for exclusion. Priority for assigning reasons for exclusions is consistent with the order in the table. N for the Placebo group will 
be the number of subjects who received Placebo for each cohort, counting the same subjects who received Placebo in Cohort 3 separately from the 
subjects who received Placebo in Cohort 6.] 
Analysis Populations 
Reason Subjects Excluded 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Safety Population 
No study product received 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
PK Analysis Population 
Any reason 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Subject received placebo 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Assigned dose not received or completed  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Subject has no measurable concentration in 
plasma or urine at any timepoint 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
PK Analysis Subset 
Any reason 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Excluded from PK Analysis Population 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
Protocol deviation(s) with potential to impact 
PK 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
 
PK data insufficient to estimate any PK 
parameters  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: N=Number of subjects enrolled/randomized.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns.   
 


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Table 11: 
Ineligibility Summary of Screen Failures 
[Implementation Note: Although subjects may meet multiple criteria for exclusion, each subject will only be counted under one reason for exclusion in 
this table. The final summary table will include only inclusion/exclusion criterion with at least 1 subject. Criteria that were not met by any subjects will 
be excluded from final table. If any of the criteria footnotes change in subsequent versions of the study protocol, the updated text should be used instead.] 
Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
Subjects Excluded 
na 
%b 
Inclusion and Exclusion 
Number of subjects failing any eligibility criterion 
x 
100 
Inclusion 
Any inclusion criterion 
x 
xx 
Willing and able to provide written informed consent and authorization for use of protected health information 
x 
xx 
Willing and able to comply with protocol requirements, instructions, and protocol-stated restrictions (including 
confinement to the CRU) and is likely to complete the study as planned 
x 
xx 
Male and female subjects, 18-45 years of age (inclusive) 
x 
xx 
Subject is in good health to be safely enrolled in this protocol and determined by medical history and physical exam 
BMI of 18-35 kg/m2, inclusive, and minimum weight of 50 kg 
If a female participant is of childbearing potentialc, she must use a highly effective contraceptive methodd from 30 days 
before enrollment through the 3 months after dosing. 
Malese having sexual intercourse with women of childbearing potential must agree to consistent use of condoms from 
study product administration through 3 months after dosingf 
Subject has adequate venous access for blood collection 
Exclusion 
Any exclusion criterion 
x 
xx 
Has a chronic condition that may increase risk to subject or interfere with endpoint assessment (e.g., liver disease, 
kidney disease, immunodeficiency) 
x 
xx 
Chronic condition diagnosed within 90 days of the Screening visit 
x 
xx 
Unstable chronic diseaseg within 6 months of the Screening visit 
x 
xx 
History of psychiatric condition that has required hospitalization in the last 5 years or patient is considered unstable by 
study investigator 
Any condition that is in the opinion of the Investigator could significantly impact drug absorption, distribution, or 
elimination 
Any out of normal range valueh at screening or enrollment (Section 8.1 and Appendix B of the protocol) 


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Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
Subjects Excluded 
na 
%b 
Abnormal ECGs. See Section 7.1 of the protocol Clinical Evaluations for exceptions 
Electrocardiographic QTcF interval >430 msec for males and >450 msec for females at Screening 
Positive test for antibodies to HIV-1, HIV-2, HBsAg, or HCV 
Positive urine drug test. The drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, 
cannabinoids, phencyclidine, and benzodiazepines 
Female subject of childbearing potential who is pregnanti, lactating, or planning to become pregnant during the study 
period or 3 months after the final dose of study product 
Received any study product in a clinical trial within 30 days prior to Screening 
Admitted or documented illicit drug use or alcohol abuse within 6 months prior to Screening or during their 
participation in the trial 
Consumed alcohol within 72 hours of Day -1, until after the visit to the CRU on Day 14 or have positive alcohol test at 
Screening or on admission to the CRU 
Tobaccoj use within 90 days prior to the Screening Visit or while a subject is enrolled in the study OR a positive drug 
test for cotinine 
Use of prescription drugs within 14 days prior to the dose of study product with the exception of hormonal 
contraceptives, which are permitted throughout the study 
Received any non-prescription medications, vitamins, or dietary supplements k within 7 days of dosing, unless prior 
approval is granted by both the Investigator and the Sponsor 
History of intolerance or hypersensitivity to azole antifungals 
Blood donation or other significant blood loss within 60 days of screening and for the duration of the study 
Inability or difficulty swallowing whole capsules/tablets and/or multiple capsules/tablets 
Consumption of beverages and foods containing caffeine for 24 hours prior to Day -1 until discharge from the CRU on 
Day 4 
Consumption of grapefruit, or juices containing grapefruit or Seville oranges within 7 days prior to the scheduled dose 
of the study product until after the visit to the CRU on Day 14 
Subject has plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of 
the investigational product at any time during the study periodl 
Having dietary restrictions that would preclude the subject from participating in either fed or fasting cohorts 


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Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
Subjects Excluded 
na 
%b 
 
Having sensitivity or allergy to aspirin 
 
 
Eligible but Not Enrolled 
Any Reason 
 
 
 
[Reason 1] 
 
 
 
[Reason 2] 
 
 
a More than one criterion may be marked per subject. 
b Denominator for proportions is the total number of screen failures. 
c A woman is considered of childbearing potential unless post-menopausal (subject is at least 50 years old and has history of > 2 years without menses without other known or suspected cause and has a 
FSH level >40 IU/L), or permanently surgically sterilized. 
d A highly effective contraceptive method includes surgical sterilization methods such as tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful tubal obliteration (e.g., 
Essure®) with documented radiological confirmation test at least 90 days after the procedure, or long-acting reversible contraception (progestin-releasing subdermal implants, copper intrauterine 
devices (IUDs), levonorgesterel-releasing IUDs. 
e Including vasectomized men. 
f And must also agree to not donate sperm during this same time period. 
g As defined by need for medical intervention that lead to a change in medications and/or required hospitalization, surgery/procedure, or ED/urgent care visit. 
h A laboratory value that is Grade 1 (with the exception of ALT, AST, Total bilirubin, hemoglobin or serum creatinine) will be allowed if not considered to be clinically significant by the investigator. 
i Having a positive serum pregnancy test at the Screening Visit or any other specified timepoint prior to the dose of the study product. 
j Tobacco use includes vaping, smoking tobacco, the use of snuff and chewing tobacco, and other nicotine or nicotine- containing products. 
k Excluded from this list is intermittent use of acetaminophen at doses of <2 g/day or ibuprofen <1200 mg/day. Herbal supplements must be discontinued 7 days prior to the dose of the study product. 
l Includes trials that have a study intervention such as a drug, biologic, or device. 


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14.1.2 Demographic Data by Study Group 
Table 12: 
Summary of Categorical Demographic and Baseline Characteristics by Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same 
subjects in Cohort 3 who continued on to Cohort 6 separately.] 
Variable 
Characteristic 
40 mg Fasted 
(N=X) 
80 mg Fasted 
(N=X) 
160 mg Fasted 
(N=X) 
160 mg Fed 
(N=X) 
320 mg Fasted 
(N=X) 
640 mg Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Sex  
Male 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Female 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
Ethnicity  
Not Hispanic or Latino 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Hispanic or Latino 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Not Reported 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Unknown 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
Race  
American Indian or Alaska Native 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Asian 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Native Hawaiian or Other Pacific Islander 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Black or African American 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
White 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Multi-Racial 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Unknown 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Not Reported 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
Notes: N=Number of subjects enrolled/randomized.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns.   


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Table 13: 
Summary of Continuous Demographic and Baseline Characteristics by Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same 
subjects in Cohort 3 who continued on to Cohort 6 separately.] 
Variable 
Statistic 
40 mg Fasted 
(N=X) 
80 mg Fasted 
(N=X) 
160 mg Fasted 
(N=X) 
160 mg Fed 
(N=X) 
320 mg Fasted 
(N=X) 
640 mg Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
Age (years) 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
SD 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
Height (cm) 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
SD 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
Weight (kg) 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
SD 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
BMI (kg/m2) 
Mean 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
SD 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Median 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
Notes: N=Number of subjects enrolled/randomized. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns.   


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14.1.3 Prior and Concurrent Medical Conditions 
Table 14: 
Summary of Subjects with Pre-Existing Medical Conditions by MedDRA System Organ Class and Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same 
subjects in Cohort 3 who continued on to Cohort 6 separately.] 
MedDRA System Organ Class 
40 mg Fasted 
(N=X) 
80 mg Fasted 
(N=X) 
160 mg Fasted 
(N=X) 
160 mg Fed 
(N=X) 
320 mg Fasted 
(N=X) 
640 mg Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any SOC 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
[SOC 1] 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
[SOC 2] 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
Notes: N=Number of subjects enrolled/randomized. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the All Subjects and Placebo columns.   
 
 


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14.4 
Summary of Concomitant Medications 
Table 15: 
Number and Percentage of Subjects with Prior Medications by WHO Drug Classification and Dose Group 
[Implementation Note: Only include prior medications, medications with an end date prior to the first dose.  
N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who received Placebo in 
Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same subjects in Cohort 3 
who continued on to Cohort 6 separately.] 
WHO Drug Code  
Level 1, Anatomic Group 
WHO Drug Code  
Level 2, Therapeutic Subgroup 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any Level 1 Codes 
Any Level 2 Codes 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
[ATC Level 1 - 1] 
Any [ATC 1 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 2] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 3] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
[ATC Level 1 - 2] 
[ATC 2 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 2] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 3] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: N=Number of subjects enrolled/randomized. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the Placebo and All Subjects columns.   
 
 


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Table 16: 
Number and Percentage of Subjects with Concurrent Medications by WHO Drug Classification and Dose Group 
[Implementation Note: Only include concomitant medications, medications that are ongoing or that have an end date after the dosing. 
N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who received Placebo in 
Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the All Subjects group will count the same subjects in Cohort 3 
who continued on to Cohort 6 separately.] 
WHO Drug Code  
Level 1, Anatomic Group 
WHO Drug Code  
Level 2, Therapeutic Subgroup 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
All Subjects 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any Level 1 Codes 
Any Level 2 Codes 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
[ATC Level 1 - 1] 
Any [ATC 1 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 2] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 3] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
[ATC Level 1 - 2] 
[ATC 2 - 1] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 2] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
  
[ATC 2 - 3] 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: N=Number of subjects enrolled/randomized.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each study part in the Placebo Dose Group. 
 
 


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 17: 
Overall Summary of Adverse Events by Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who 
received Placebo in Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the Any Dose group will count the same 
subjects in Cohort 3 who continued on to Cohort 6 separately.] 
Subjects meeting at least one of the below conditions 
Any 
Dose 
(N=X) 
40 mg 
Fasted 
(N=X) 
80 mg 
Fasted 
(N=X) 
160 mg 
Fasted 
(N=X) 
160 mg 
Fed 
(N=X) 
320 mg 
Fasted 
(N=X) 
640 mg 
Fasted 
(N=X) 
Placebo 
(N=X) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
At least one adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one related adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one mild (or worse) related adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one moderate (or worse) related adverse event    
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one severe related adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one serious adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one related, serious adverse event 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
At least one adverse event leading to early termination 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
x (%) 
Notes: N=Number of subjects in the Safety Population in each Dose Group. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the Any Dose and Placebo columns.   
Subjects are only counted once for each category, Dose Group, and study part, regardless of the number of events. 


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Table 18: 
Adverse Events Occurring in 5% of Subjects in Any Dose Group by MedDRA System Organ Class, Preferred Term, and Dose 
Group - Safety Population 
[Implementation Note: If there is only 1 PT for an SOC, there will be no “Any PT” row. Abnormal laboratory AEs assessed using the protocol toxicity 
tables will not be included in this summary. 
N for the Placebo group will be the number of subjects who received Placebo for each cohort, counting the same subjects who received Placebo in 
Cohort 3 separately from the subjects who received Placebo in Cohort 6. Similarly, N for the Any Dose group will count the same subjects in Cohort 3 
who continued on to Cohort 6 separately.] 
MedDRA 
System 
Organ 
Class 
MedDRA 
High Level 
Group 
Term 
MedDRA 
Preferred 
Term 
Any Dose 
(N=X) 
40 mg Fasted  
(N=X) 
80 mg Fasted  
(N=X) 
160 mg Fasted  
(N=X) 
160 mg Fed  
(N=X) 
320 mg Fasted  
(N=X) 
640 mg Fasted  
(N=X) 
Placebo 
(N=X) 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
n (%) 
Num. 
of 
Events 
Serious Adverse Events 
Any SOC 
Any HLGT 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
Any HLGT 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
HLGT1 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
HLGT1 
PT1 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
 
Etc. 
 
Etc. 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
Other (Non-serious) Adverse Events 
Any SOC 
Any HLGT 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
Any HLGT 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
HLGT1 
Any PT 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
SOC1 
HLGT1 
PT1 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
Etc. 
 
Etc. 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
x (x) 
x 
Notes: N=Number of subjects in the Safety Population in each Dose Group. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the Any Dose and Placebo columns.    
n=number of subjects reporting adverse events. 
  


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14.3.1.2 
Unsolicited Adverse Events 
Table 19: 
Summary of Unsolicited Adverse Events by MedDRA System Organ Class and Preferred 
Term, Dose Number, and Dose Group  
[Implementation Note: If there is only 1 PT for an SOC, there will be no “Any PT” row. 
N for the Any Dose Group will be the number of subjects who received VT-1598 for each cohort, counting 
the same subjects who received VT-1598 in Cohort 3 separately from the subjects who received VT-1598 in 
Cohort 6. Similarly, N for the Placebo group will count the same subjects in Cohort 3 who continued on to 
Cohort 6 separately. 
Dose Group order: Any Dose, 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 
mg Fasted, Placebo]  
Dose Group 
MedDRA System 
Organ Class 
MedDRA High Level 
Group Term 
MedDRA Preferred 
Term 
n (%) 
95% CIa 
Number of 
Events 
Any Dose (N=X) 
Any SOC 
Any HLGT 
Any PT 
x (x) 
xx, xx 
x 
 
[SOC 1] 
Any HLGT 
Any PT 
x (x) 
xx, xx 
x 
 
 
HLGT1 
Any PT 
x (x) 
xx, xx 
x 
 
 
 
[PT 1] 
x (x) 
xx, xx 
x 
 
[SOC 2] 
Any HLGT 
Any PT 
x (x) 
xx, xx 
x 
 
 
HLGT1 
Any PT 
x (x) 
xx, xx 
x 
 
 
 
[PT 1] 
x (x) 
xx, xx 
x 
40 mg Fasted 
(N=X) 
… 
 
… 
x (x) 
xx, xx 
x 
… 
… 
 
… 
x (x) 
xx, xx 
x 
Placebo (N=X) 
… 
 
… 
x (x) 
xx, xx 
x 
Notes: N=Number of subjects in the Safety Population in the specified Dose Group. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each dosing period in the Any Dose Group and the 
Placebo Dose Group. 
n=number of subjects reporting adverse events within each SOC/PT. 
A subject is only counted once per PT per Dose Group and dosing period. 
a Exact Clopper-Pearson Confidence Interval. 
 
 


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Table 20: 
Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, 
Maximum Severity, Relationship, and Dose Group 
[Implementation Note: N for the Placebo group will be the number of subjects who received Placebo for each 
cohort, counting the same subjects who received Placebo in Cohort 3 separately from the subjects who 
received Placebo in Cohort 6. Similarly, N for the Any Dose group will count the same subjects in Cohort 3 
who continued on to Cohort 6 separately. 
Dose Group order: Any Dose, 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 
mg Fasted, Placebo]  
Dose Group 
MedDRA System 
Organ Class 
MedDRA High Level 
Group Term 
MedDRA 
Preferred Term  
Severity 
Related  
n (%) 
Not Related  
n (%) 
Total  
n (%) 
Any Dose 
(N=X) 
Any SOC 
Any HLGT 
Any PT 
Any Severity 
x (%) 
x (%) 
x (%) 
  
  
 
  
Mild 
x (%) 
x (%) 
x (%) 
  
  
 
  
Moderate 
x (%) 
x (%) 
x (%) 
  
  
 
  
Severe 
x (%) 
x (%) 
x (%) 
  
[SOC 1] 
Any HLGT 
Any PT 
Any Severity 
x (%) 
x (%) 
x (%) 
  
  
 
  
… 
x (%) 
x (%) 
x (%) 
  
  
HLGT1 
Any PT 
Any Severity 
x (%) 
x (%) 
x (%) 
  
  
 
  
… 
x (%) 
x (%) 
x (%) 
 
  
HLGT1 
[PT1] 
Any Severity 
x (%) 
x (%) 
x (%) 
 
  
 
  
… 
x (%) 
x (%) 
x (%) 
40 mg Fasted 
(N=X) 
Any SOC 
 
Any PT 
Any Severity 
x (%) 
x (%) 
x (%) 
… 
… 
 
… 
… 
x (%) 
x (%) 
x (%) 
Placebo 
(N=X) 
… 
 
… 
… 
x (%) 
x (%) 
x (%) 
Notes: N=Number of subjects in the Safety Population in each Dose Group. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are summarized separately for each dosing period in the Any Dose Group and the 
Placebo Dose Group.  
Subjects who only participated in one study part are only counted once per PT and Dose Group, in the highest reported severity. 
 
 


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14.3.2 Listing of Deaths, Other Serious and Significant Adverse Events 
Table 21: 
Listing of Serious Adverse Events 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. If the event is ongoing (no stop 
date), indicate “ongoing” for the “Duration of AE in Days”. If more than one reason is selected for the reason reported as an SAE, list all reasons in the 
column separated by a comma. In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate etiology, separate by a 
colon. Listing should be sorted by Dose Group, Subject ID, and AE Number. 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo]  
Adverse 
Event 
MedDRA 
System 
Organ 
Class 
MedDRA 
Higher Level 
Group Term  
MedDRA 
Preferred 
Term 
No. of 
Days Post 
Dose 
Duration 
of AE in 
Days 
No. of Days Post 
Dose the Event 
Became Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship to 
Study Treatment: 
Alternate Etiology 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Dose Group: , Subject ID: , AE Number: 
  
  
  
 
  
  
  
  
  
  
  
  
  
Comments:  
Dose Group: , Subject ID: , AE Number: 
  
  
  
 
  
  
  
  
  
  
  
  
  
Comments:  
 
 


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Table 22: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. If the event is ongoing (no stop 
date), indicate “ongoing” for the “Duration of AE in Days”. . Listing should be sorted by Dose Group, Subject ID, and AE Number. 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo]  
Adverse 
Event 
MedDRA 
System 
Organ Class 
MedDRA 
Higher Level 
Group Term 
MedDRA 
Preferred 
Term 
No. of Days 
Post Dose 
Duration of 
AE in Days 
Severity 
Relationship to 
Study Treatment 
(Alternate Etiology) 
Action Taken with 
Study Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
 
Dose Group: , Subject ID: , AE Number: 
  
  
 
  
  
  
  
  
  
  
  
Comments:  
 
Dose Group: , Subject ID: , AE Number: 
  
  
 
  
  
  
  
  
  
  
  
Comments:  
 


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14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events 
(not included in SAP, but this is a placeholder for the CSR) 
 


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14.3.4 Abnormal Laboratory Value Listings (by Subject) 
Table 23: 
Listing of Abnormal Laboratory Results – Chemistry 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. This listing includes all abnormal 
Chemistry results (laboratory results outside of the normal range defined in the protocol). Normal chemistry results for other parameters that occurred on 
the same visit as the abnormal result will not be listed. There is a separate, complete listing of all Chemistry results in Appendix 3. In the Laboratory 
Parameter column, indicate the units in parentheses after the parameter, e.g., Sodium (mEq/L). This listing is not color-coded, but the severity should be 
included in parentheses after the result, e.g., 133 (Mild). Results that are outside the normal range but not mild, moderate, or severe will have (ONR) as 
the severity included after the result. Results that meet grading criteria of mild, moderate, or severe but which are not treatment emergent (not worse than 
baseline, as described in Section 9.6) will be shown as “ONR”. 
Sort order: Dose Group, Subject ID, Timepoint, and Parameter. 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo. 
Parameter order: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium, chloride, total protein, creatinine, triglycerides, total cholesterol, 
low-density lipoprotein, high-density lipoprotein, total carbon dioxide, creatine phosphokinase, phosphorus, alkaline phosphatase, aspartate 
aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, magnesium, gamma-glutamyl transferase (GGT), serum cortisol] 
Dose Group 
Subject ID 
Sex 
Age (years) 
Timepoint 
Date of Assessment 
Laboratory Parameter 
(Units) 
Result (Severity) 


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Table 24: 
Listing of Abnormal Laboratory Results – Hematology 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. This listing includes all abnormal 
Hematology results (laboratory results outside of the normal range defined in the protocol). Normal hematology results for other parameters that 
occurred on the same visit as the abnormal result will not be listed. There is a separate, complete listing of all Hematology results in Appendix 3. In the 
Laboratory Parameter column, indicate the units in parentheses after the parameter, e.g., Hemoglobin (g/dL). This listing is not color-coded, but the 
severity should be included in parentheses after the result, e.g., 10.5 (Moderate). Results that are outside the normal range but not mild, moderate, or 
severe will have (ONR) as the severity included after the result. Results that meet grading criteria of mild, moderate, or severe but which are not 
treatment emergent (not worse than baseline, as described in Section 9.6) will be shown as “ONR”. 
Sort order: Dose Group, Subject ID, Timepoint, and Parameter 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo. 
Parameter order: hemoglobin, hematocrit, lymphocytes, neutrophils, monocytes, eosinophils, basophils, platelet, red blood cell count, and white blood 
cell count.] 
Dose Group 
Subject ID 
Sex 
Age (years) 
Timepoint 
Date of Assessment 
Laboratory Parameter 
(Units) 
Result (Severity) 


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Table 25: 
Listing of Abnormal Laboratory Results - Coagulation 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. This listing includes all abnormal 
Coagulation results (laboratory results outside of the normal range defined in the protocol). Normal coagulation results for other parameters that occurred 
on the same visit as the abnormal result will not be listed. There is a separate, complete listing of all Coagulation results in Appendix 3. In the Laboratory 
Parameter column, indicate the units in parentheses after the parameter, e.g., Prothrombin Time (s). This listing is not color-coded, but the severity 
should be included in parentheses after the result, e.g., 10.5 (Moderate). Results that are outside the normal range but not mild, moderate, or severe will 
have (ONR) as the severity included after the result. Results that meet grading criteria of mild, moderate, or severe but which are not treatment emergent 
(not worse than baseline, as described in Section 9.6) will be shown as “ONR”. 
Sort order: Dose Group, Subject ID, Timepoint, and Parameter. 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo. 
Parameter order: aPTT, PT, INR.] 
Dose Group 
Subject ID 
Sex 
Age (years) 
Timepoint 
Date of Assessment 
Laboratory Parameter 
(Units) 
Result (Severity) 


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Table 26: 
Listing of Abnormal Laboratory Results - Urinalysis 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. This listing includes all abnormal 
Urinalysis results (laboratory results outside of the normal range defined in the protocol). Normal urinalysis results for other parameters that occurred on 
the same visit as the abnormal result will not be listed. There is a separate, complete listing of all Urinalysis results. In the Laboratory Parameter column, 
indicate the units in parentheses after the parameter, e.g., Red Blood Cells (/HPF). This listing is not color-coded, but the severity should be included in 
parentheses after the result, e.g., 10.5 (Moderate). Results that are outside the normal range but not mild, moderate, or severe will have (ONR) as the 
severity included after the result. Results that meet grading criteria of mild, moderate, or severe but which are not treatment emergent (not worse than 
baseline, as described in Section 9.6) will be shown as “ONR”. Method should describe the type of urinalysis done, dipstick or microscopic test. 
Sort order: Dose Group, Subject ID, Timepoint, Parameter, and Method. 
Dose Group order: 40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted, Placebo. 
Parameter order: specific gravity, pH, occult blood, leukocyte esterase, RBC, WBC] 
Dose Group 
Subject ID 
Sex 
Age (years) 
Timepoint 
Date of Assessment 
Laboratory Parameter 
(Units) 
Result (Severity) 


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14.3.5 Displays of Laboratory Results 
14.3.5.1 
Chemistry Results 
Table 27: 
Chemistry Abnormal Results by Parameter, Dose Group, and Timepoint 
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dosing period in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dosing period in the Placebo Dose Group. 
Parameter order: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium, chloride, total protein, 
creatinine, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, total carbon 
dioxide, creatine phosphokinase, phosphorus, alkaline phosphatase, aspartate aminotransferase, alanine 
aminotransferase, total bilirubin, direct bilirubin, magnesium, gamma-glutamyl transferase (GGT), serum 
cortisol] 
Dose Group 
Timepoint 
N 
Abnormal, Low 
Abnormal, High 
n 
% 
n 
% 
Chemistry - Any Parameter 
 
 
 
 
 
 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
 
Day 4 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
Day 7 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
Day 14 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
Day 21 
x 
x (x) 
x (x) 
x (x) 
x (x) 
40 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
80 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg  Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg Fed 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
320 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
640 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
Placebo 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
Albumin  
 
 
 
 
 
 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
x (x) 
… 
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
Note: N=Number of subjects in the Safety Population with the laboratory result assessed at the respective timepoint.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each dosing period in both the Any Dose Group and 
the Placebo Dose Group. 


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Table 28: 
Chemistry Laboratory Toxicity Grade by Parameter, Dose Group, Timepoint, and 
Severity 
[Implementation Note: If there is not at least one Mild, Moderate, or Severe event for a Dose Group within a 
parameter, then only the Maximum Severity Post Baseline row will be shown for that parameter. Only include 
chemistry parameters with grading criteria in the protocol. Toxicities representing an increase in the 
laboratory result will be summarized separately from decreases. For example, there will be one row for 
“Sodium, Decrease” and another for “Sodium, Increase”. Subjects who received VT-1598 in both Cohorts 3 
and 6 will be included separately for each dosing period in the Any Dose Group. Similarly, subjects who 
received placebo in both Cohorts 3 and 6 will be included separately for each dosing period in the Placebo 
Dose Group. 
Parameter order: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium, chloride, total protein, 
creatinine, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, total carbon 
dioxide, creatine phosphokinase, phosphorus, alkaline phosphatase, aspartate aminotransferase, alanine 
aminotransferase, total bilirubin, direct bilirubin, magnesium, gamma-glutamyl transferase (GGT), serum 
cortisol. Decrease parameters will always be listed before increase parameters, if applicable] 
Dose Group 
Timepoint 
N 
Mild 
Moderate 
Severe 
n (%) 
n (%) 
n (%) 
Chemistry - Any Parameter 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
 
Maximum Severity Post Baseline 
x 
x (x) 
x (x) 
x (x) 
 
Day 4 
x 
x (x) 
x (x) 
x (x) 
  
Day 7 
x 
x (x) 
x (x) 
x (x) 
  
Day 14 
x 
x (x) 
x (x) 
x (x) 
  
Day 21  
x 
x (x) 
x (x) 
x (x) 
40 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
80 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg  Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg Fed 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
320 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
640 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Placebo 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Albumin, Decrease  
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
… 
… 
x 
x (x) 
x (x) 
x (x) 
Notes: The “Maximum Severity Post Baseline” rows indicate the maximum severity experienced by each subject at any timepoint post 
baseline, including unscheduled assessments. 
N=Number of subjects in the Safety Population with the laboratory result assessed at the respective timepoint. Results from subjects in Cohort 
3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the Placebo Dose Group. 


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Table 29: 
Chemistry Summary Statistics Change from Baseline by Parameter, Dose Group, and 
Timepoint 
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dosing period in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dosing period in the Placebo Dose Group. 
Mean, SD, and median will be reported to one decimal place greater than the original data. Min and max 
values will be reported with the same number of decimal places as the original data. 
Parameter order: albumin, glucose, blood urea nitrogen, potassium, calcium, sodium, chloride, total protein, 
creatinine, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, total carbon 
dioxide, creatine phosphokinase, phosphorus, alkaline phosphatase, aspartate aminotransferase, alanine 
aminotransferase, total bilirubin, direct bilirubin, magnesium, gamma-glutamyl transferase (GGT), serum 
cortisol] 
Dose Group 
Timepoint 
N 
Change from Baseline 
Mean 
SD 
Median 
Min, Max 
Albumin (g/dL) 
Any Dose 
Day 4 
x 
x 
x 
x 
x, x 
  
Day 7 
x 
x 
x 
x 
x, x 
  
Day 14 
x 
x 
x 
x 
x, x 
  
Day 21 
x 
x 
x 
x 
x, x 
40 mg Fasted 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
80 mg Fasted 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg Fasted 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg Fed 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
320 mg Fasted 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
640 mg Fasted 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
Placebo 
Day 4 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
Glucose (mg/dL) 
Any Dose 
Day 4 
x 
x 
x 
x 
x, x 
… 
… 
x 
x (x) 
x (x) 
x (x) 
x (x) 
…  
Notes: N=Number of subjects in the Safety Population with the laboratory result assessed at the respective timepoint. Results from subjects in 
Cohort 3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the Placebo Dose Group. 
 


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14.3.5.2 
Hematology Results 
Table 30: 
Hematology Abnormal Results by Parameter, Dose Group, and Timepoint 
[Parameter order: hemoglobin, hematocrit, lymphocytes, neutrophils, monocytes, eosinophils, basophils, 
platelet, red blood cell count, white blood cell count] 
This table will repeat Table 27 for Hematology Parameters 
 
Table 31: 
Hematology Laboratory Toxicity Grade by Parameter, Dose Group, Timepoint, and 
Severity 
[Parameter order: hemoglobin, hematocrit, lymphocytes, neutrophils, monocytes, eosinophils, basophils, 
platelet, red blood cell count, white blood cell count.] 
This table will repeat Table 28 for Hematology Parameters 
 
Table 32: 
Hematology Summary Statistics Change from Baseline by Parameter, Dose Group, and 
Timepoint 
[Parameter order: hemoglobin, hematocrit, lymphocytes, neutrophils, monocytes, eosinophils, basophils, 
platelet, red blood cell count, white blood cell count.] 
This table will repeat Table 29 for Hematology Parameters 
 
 


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14.3.5.3 
Coagulation Results 
Table 33: 
Coagulation Abnormal Results by Parameter, Dose Group, and Timepoint 
[Parameter order: activated partial thromboplastin time, prothrombin time, international normalized ratio.] 
This table will repeat Table 27 for Coagulation Parameters 
 
Table 34: 
Coagulation Laboratory Toxicity Grade by Parameter, Dose Group, Timepoint, and 
Severity 
[Parameter order: activated partial thromboplastin time, prothrombin time, international normalized ratio.] 
This table will repeat Table 28 for Coagulation Parameters 
 
Table 35: 
Coagulation Summary Statistics Change from Baseline by Parameter, Dose Group, and 
Timepoint 
[Parameter order: activated partial thromboplastin time, prothrombin time, international normalized ratio.] 
This table will repeat Table 29 for Coagulation Parameters 
 


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14.3.5.4 
Urinalysis Results 
Table 36: 
Urinalysis Abnormal Results by Parameter, Dose Group, and Timepoint 
[Parameter order: specific gravity, pH, occult blood, leukocyte esterase, urine RBC, and urine WBC] 
This table will repeat Table 27 for Urinalysis Parameters 
 
Table 37: 
Urinalysis Laboratory Toxicity Grade by Parameter, Dose Group, Timepoint, and 
Severity 
[Parameter order: specific gravity, pH, leukocyte esterase, urine RBC, and urine WBC]  
This table will repeat Table 28 for Urinalysis Parameters 
 
Table 38: 
Urinalysis Summary Statistics Change from Baseline by Parameter, Dose Group, and 
Timepoint 
[Parameter order: specific gravity and pH.] 
This table will repeat Table 29 for Urinalysis Parameters (specific gravity and pH only) 
 


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14.3.6 Displays of Vital Signs 
Table 39: 
Vital Sign Toxicity Grade by Parameter, Dose Group, Timepoint, and Severity 
[Implementation Note: If there is not at least one Mild, Moderate, or Severe event for a Dose Group within a 
parameter, then only the Maximum Severity Post Baseline row will be shown for that parameter. Summarize 
increase results separately from decrease results. For example, there will be one row for “Pulse, Decrease” 
and another for “Pulse, Increase”. Subjects who received VT-1598 in both Cohorts 3 and 6 will be included 
separately for each dosing period in the Any Dose Group. Similarly, subjects who received placebo in both 
Cohorts 3 and 6 will be included separately for each dosing period in the Placebo Dose Group. 
Parameter order: systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, temperature] 
Dose Group 
Timepoint 
N 
Mild 
Moderate 
Severe 
n (%) 
n (%) 
n (%) 
Any Parameter 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
 
Maximum Severity Post Baseline 
x 
x (x) 
x (x) 
x (x) 
  
Day 1, 1 h Post Dose 
x 
x (x) 
x (x) 
x (x) 
  
Day 1, 2 h Post Dose 
x 
x (x) 
x (x) 
x (x) 
  
Day 1, 4 h Post Dose 
x 
x (x) 
x (x) 
x (x) 
  
Day 1, 8 h Post Dose 
x 
x (x) 
x (x) 
x (x) 
  
Day 2  
x 
x (x) 
x (x) 
x (x) 
  
Day 3 
x 
x (x) 
x (x) 
x (x) 
  
Day 4  
x 
x (x) 
x (x) 
x (x) 
  
Day 7 
x 
x (x) 
x (x) 
x (x) 
  
Day 14  
x 
x (x) 
x (x) 
x (x) 
  
Day 21 
x 
x (x) 
x (x) 
x (x) 
40 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
80 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg  Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg Fed 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
320 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
640 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Placebo 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Pulse, Decrease (bpm) 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
… 
… 
x 
x (x) 
x (x) 
x (x) 
… 
Notes: The “Maximum Severity Post Baseline” rows indicate the maximum severity experienced by each subject at any timepoint post 
baseline, including unscheduled assessments. 
N=Number of subjects in the Safety Population with the vital sign assessed at the respective timepoint.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the 
Placebo Dose Group. 


Statistical Analysis Plan - DMID Protocol: 17-0087 
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Table 40: 
Vital Sign Change from Baseline by Parameter, Dose Group, and Timepoint  
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dosing period in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dosing period in the Placebo Dose Group. 
Mean, SD, and median will be reported to one decimal place greater than the original data. Min and max 
values will be reported with the same number of decimal places as the original data. 
Parameter order: systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, temperature] 
Dose Group 
Timepoint 
N 
Change from Baseline 
Mean 
SD 
Median 
Min, Max 
Systolic Blood Pressure 
Any Dose 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
Day 1, 2 h Post Dose 
x 
x 
x 
x 
x, x 
  
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
Day 1, 8 h Post Dose 
x 
x 
x 
x 
x, x 
  
Day 2  
x 
x 
x 
x 
x, x 
  
Day 3 
x 
x 
x 
x 
x, x 
  
Day 4  
x 
x 
x 
x 
x, x 
  
Day 7 
x 
x 
x 
x 
x, x 
  
Day 14  
x 
x 
x 
x 
x, x 
  
Day 21 
x 
x 
x 
x 
x, x 
40 mg Fasted 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
80 mg Fasted 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg  Fasted 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg Fed 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
320 mg Fasted 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
640 mg Fasted 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
Placebo 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
Pulse, Increase (bpm) 
Any Dose 
Day 1, 1 h Post Dose 
x 
x 
x 
x 
x, x 
… 
… 
x 
x  
x  
x  
x, x  
…  
Notes: N=Number of subjects in the Safety Population with the vital sign assessed at the respective timepoint. Results from subjects in Cohort 3 
that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the Placebo Dose Group. 
 


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14.3.7 Displays of ECG Measurements 
Table 41: 
Summary of Post Dose ECG Change in Overall Interpretations from Baseline by Dose Group and Timepoint   
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately for each dose received in the Any Dose 
Group. Similarly, subjects who received placebo in both Cohorts 3 and 6 will be included separately for each dose received in the Placebo Dose Group.] 
Change from Baseline in ECG Interpretation 
Any Dose 
n (%) 
40 mg Fasted  
n (%) 
80 mg Fasted  
n (%) 
160 mg Fasted  
n (%) 
160 mg Fed  
n (%) 
320 mg Fasted  
n (%) 
640 mg Fasted  
n (%) 
Placebo  
n (%) 
Day 1, 4 h Post Dose 
N 
x 
x 
x 
x 
x 
x 
x 
x 
Normal at Both Times 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Normal to Abnormal, NCS 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Normal to Abnormal, CS 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Day 4 
N 
x 
x 
x 
x 
x 
x 
x 
x 
Normal at Both Times 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
… 
  
  
  
  
  
  
  
  
Day 21 
N 
x 
x 
x 
x 
x 
x 
x 
x 
Normal at Both Times 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
… 
  
  
  
  
  
  
  
  
Notes: N=Number of subjects in the Safety Population with ECG measurements at the timepoints indicated.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the Placebo Dose Group. 
NCS = Not clinically significant, CS = Clinically significant. 
 
 


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Table 42: 
ECG Toxicity Grade by Parameter, Severity, Dose Group, and Timepoint 
[Implementation Note: If there is not at least one Mild, Moderate, or Severe event for a Dose Group within a 
parameter, then only the Maximum Severity Post Baseline row will be shown for that parameter. Subjects 
who received VT-1598 in both Cohorts 3 and 6 will be included separately for each dosing period in the Any 
Dose Group. Similarly, subjects who received placebo in both Cohorts 3 and 6 will be included separately for 
each dosing period in the Placebo Dose Group.] 
Dose Group 
Timepoint 
N 
Mild 
Moderate 
Severe 
n (%) 
n (%) 
n (%) 
QTcF Interval (msec) 
Any Dose 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
Maximum Severity Post Baseline 
x 
x (x) 
x (x) 
x (x) 
  
Day 1, 4h Post Dose 
x 
x (x) 
x (x) 
x (x) 
  
Day 4 
x 
x (x) 
x (x) 
x (x) 
  
Day 21 
x 
x (x) 
x (x) 
x (x) 
40 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
80 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
160 mg Fed 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
320 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
640 mg Fasted 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Placebo 
Baseline 
x 
x (x) 
x (x) 
x (x) 
  
… 
x 
x (x) 
x (x) 
x (x) 
Notes: The "Maximum Severity Post Baseline" row indicates the maximum severity of ECG results experienced across all subjects at any 
timepoint post baseline, including unscheduled assessments.  
N=Number of subjects in the Safety Population with ECG results assessed at the respective timepoint.  
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the 
Placebo Dose Group. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
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Table 43: 
ECG Change from Baseline by Parameter, Severity, Dose Group, and Timepoint  
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dosing period in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dosing period in the Placebo Dose Group. 
Parameter order: PR Interval, QRS Duration, QT Interval, QTcF Interval, RR Interval, Mean Ventricular 
Heart Rate.] 
Dose Group 
Timepoint 
N 
Change from Baseline 
Mean 
SD 
Median 
Min, Max 
PR Interval (msec) 
Any Dose 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
Day 4 
x 
x 
x 
x 
x, x 
  
Day 21 
x 
x 
x 
x 
x, x 
40 mg Fasted 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
80 mg Fasted 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg  Fasted 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
160 mg Fed 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
320 mg Fasted 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
640 mg Fasted 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
Placebo 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
  
… 
x 
x 
x 
x 
x, x 
QRS Duration (msec) 
Any Dose 
Day 1, 4 h Post Dose 
x 
x 
x 
x 
x, x 
… 
… 
x 
x 
x 
x 
x, x 
… 
Notes: N=Number of subjects in the Safety Population with ECG measurements at the respective timepoint. 
Results from subjects in Cohort 3 that continued on to Cohort 6 are counted separately for each study part in both the Any Dose Group and the 
Placebo Dose Group. 


Statistical Analysis Plan - DMID Protocol: 17-0087 
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Table 44: 
Categorical Summary of QTcF by Dose Group and Timepoint 
[Implementation Note: For all QTcF categories that specified gender, N based on gender should be used for calculating proportions] 
QTcF Category 
Timepoint 
N 
Any Dose 
40 mg  
Fasted 
80 mg 
Fasted 
160 mg  
Fasted 
160 mg  
Fed 
320 mg 
 Fasted 
640 mg 
Fasted 
Placebo 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
QTcF >450 ms, Male 
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Day 7 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
Day 21 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
QTcF >470 ms, Female 
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
… 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
QTcF >480 ms 
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
… 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
QTcF >500 ms 
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
… 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
30 ms ≤ QTcF increases from baseline 
< 60 ms  
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
… 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
QTcF increases from baseline ≥ 60 ms 
Day 1, 4 h Post-Dose 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
 
… 
x 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
x (xx) 
Note: N=Number of subjects in Safety Population with the ECG results assessed at the respective timepoint. N is calculated based on specified sex for “QTcF >450 ms, Male” and “QTcF >470 ms, 
Female” categories.  


Statistical Analysis Plan - DMID Protocol: 17-0087 
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Table 45: 
VT-1598 Concentrations in Plasma by Dose Group – 0 h to 14 h Post Dose 
  
Nominal Timea (h) 
Dose Group 
0 
0.5 
1.5 
2 
3 
4 
6 
8 
10 
12 
14 
40 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
80 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg Fed  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
320 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
640 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: Concentrations are reported in units of ng/mL. 
Values of GM (CV %) are shown. 
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
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Table 46: 
VT-1598 Concentrations in Plasma by Dose Group – 24 h to 480 h Post Dose 
  
Nominal Timea (h) 
Dose Group 
24 
36 
48 
60 
72 
144 
312 
480 
40 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
80 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
160 mg Fed  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
320 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
640 mg Fasted  
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Notes: Concentrations are reported in units of ng/mL. 
Values of GM (CV %) are shown. 
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 96 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 47: 
VT-1598 Concentrations in Plasma, SAD 40 mg Fasted Dose Group – 0 h to 14 h Post Dose 
[Implementation Note: Mark concentrations collected out of window with an asterisk (*) next to the concentration and include a footnote before the   
Samples collected out of window are noted by an asterisk (*).  
Mark concentrations collected substantially out of window with two asterisks (**) next to the concentration and include a footnote:  
Samples collected substantially out of window are noted by two asterisks (**).  
Mark imputed concentration times with three asterisks (***) next to the concentration and include a footnote:  
Samples with imputed collection times are noted by three asterisks  (***). ] 
  
Nominal Timea (h) 
Subject ID 
0 
0.5 
1.5 
2 
3 
4 
6 
8 
10 
12 
14 
PHU.00123 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PHU.00124 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PHU.00125 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
… 
  
  
  
  
  
  
  
  
  
  
  
Statistics 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Nb 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GM 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CV % 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Notes: Concentrations are reported in units of ng/ml. 
[Out of window footnotes here, if applicable] 
a Times are relative to time of dosing. 
b Number of data points used to compute the summary statistics. For calculation of summary statistics, BQL values were imputed as 0 if the sample was taken before the first measurable PK sample 
with a concentration above the LLOQ.  BQL values were treated as missing otherwise.  
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 97 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 48: 
VT-1598 Concentrations in Plasma, SAD 40 mg Fasted Dose Group – 24 h to 480 h Post Dose 
  
Nominal Timea (h) 
Subject ID 
24 
36 
48 
60 
72 
144 
312 
480 
PHU.00123 
x 
x 
x 
x 
x 
x 
x 
x 
PHU.00124 
x 
x 
x 
x 
x 
x 
x 
x 
PHU.00125 
x 
x 
x 
x 
x 
x 
x 
x 
… 
  
  
  
  
  
  
  
  
Statistics 
x 
x 
x 
x 
x 
x 
x 
x 
Nb 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
SD 
x 
x 
x 
x 
x 
x 
x 
x 
GM 
x 
x 
x 
x 
x 
x 
x 
x 
CV % 
x 
x 
x 
x 
x 
x 
x 
x 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
Note: Concentrations are reported in units of ng/mL. 
a Times are relative to time of dosing. 
b Number of data points used to compute the summary statistics. For calculation of summary statistics, BQL values were imputed as 0 if the sample was taken before the first measurable PK sample 
with a concentration above the LLOQ.  BQL values were treated as missing otherwise. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 98 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 49: 
VT-1598 Concentrations in Plasma, 80 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for the 80 mg Fasted Dose Group  
 
Table 50: 
VT-1598 Concentrations in Plasma, 80 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for the 80 mg Fasted Dose Group 
 
Table 51: 
VT-1598 Concentrations in Plasma, 160 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for the 160 mg Fasted Dose Group 
 
Table 52: 
VT-1598 Concentrations in Plasma, 160 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for the 160 mg Fasted Dose Group 
 
Table 53: 
VT-1598 Concentrations in Plasma, 160 mg Fed Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for the 160 mg Fed Dose Group 
 
Table 54: 
VT-1598 Concentrations in Plasma, 160 mg Fed Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for the 160 mg Fed Dose Group 
 
Table 55: 
VT-1598 Concentrations in Plasma, 320 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for the 320 mg Fasted Dose Group 
 
Table 56: 
VT-1598 Concentrations in Plasma, 320 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for the 320 mg Fasted Dose Group 
 
Table 57: 
VT-1598 Concentrations in Plasma, 640 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for the 640 mg Fasted Dose Group 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 99 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 58: 
VT-1598 Concentrations in Plasma, 640 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for the 640 mg Fasted Dose Group 
 
Table 59: 
VT-11134 Concentrations in Plasma by Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 45 for VT-11134 concentrations in plasma, by Dose Group 
 
Table 60: 
VT-11134 Concentrations in Plasma by Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 46 for VT-11134 concentrations in plasma, by Dose Group 
 
Table 61: 
VT-11134 Concentrations in Plasma, 40 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 40 mg Fasted Dose Group 
 
Table 62: 
VT-11134 Concentrations in Plasma, 40 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 40 mg Fasted Dose Group  
 
Table 63: 
VT-11134 Concentrations in Plasma, 80 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 80 mg Fasted Dose Group 
 
Table 64: 
VT-11134 Concentrations in Plasma, 80 mg Fasted Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 80 mg Fasted Dose Group 
 
Table 65: 
VT-11134 Concentrations in Plasma, 160 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 160 mg Fasted Dose Group 
 
Table 66: 
VT-11134 Concentrations in Plasma, 160 mg Fasted Dose Group – 24 h to 480 h Post 
Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 160 mg Fasted Dose Group 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 100 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 67: 
VT-11134 Concentrations in Plasma, 160 mg Fed Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 160 mg Fed Dose Group 
 
Table 68: 
VT-11134 Concentrations in Plasma, 160 mg Fed Dose Group – 24 h to 480 h Post Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 160 mg Fed Dose Group  
 
Table 69: 
VT-11134 Concentrations in Plasma, 320 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 320 mg Fasted Dose Group 
 
Table 70: 
VT-11134 Concentrations in Plasma, 320 mg Fasted Dose Group – 24 h to 480 h Post 
Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 320 mg Fasted Dose Group 
 
Table 71: 
VT-11134 Concentrations in Plasma, 640 mg Fasted Dose Group – 0 h to 14 h Post Dose 
This table will repeat Table 47 for VT-11134 concentrations in plasma for the 640 mg Fasted Dose Group 
 
Table 72: 
VT-11134 Concentrations in Plasma, 640 mg Fasted Dose Group – 24 h to 480 h Post 
Dose 
This table will repeat Table 48 for VT-11134 concentrations in plasma for the 640 mg Fasted Dose Group 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 73: 
Summary Statistics for VT-1598 PK Parameters in Plasma by Dose Group 
PK Parameter (Units) 
40 mg Fasted 
80 mg Fasted 
160 mg Fasted 
160 mg Fed 
320 mg Fasted 
640 mg Fasted 
Cmax, (ng/mL) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Cmax/Dose, ((ng/mL)/mg) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Tmax, (h) 
x (x - x) 
x (x - x) 
x (x - x) 
x (x - x) 
x (x - x) 
x (x - x) 
AUC(0-last), (ng*h/mL) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
AUC(0-last), Dose ((ng*h/mL)/mg) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
AUC(0-inf),( ng*h/mL) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
AUC(0-inf)/Dose, ((ng*h/mL)/mg) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
λz, (1/h ) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
t1/2, (h) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
CL/F, (L/h) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Vd/F, ( L) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Note: Values of GM (CV %) are shown, except for Tmax for which values of median (min-max) are shown. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 102 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 74: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 40 mg Fasted Dose Group 
Statistics 
Cmax 
(ng/mL) 
Cmax/Dose 
((ng/mL)/mg) 
Tmax 
(h) 
AUC0-last 
(ng*h/mL) 
AUC0-last/Dose 
((ng*h/mL)/)/mg) 
AUC0-inf 
(ng*h/mL) 
AUC0-inf/Dose 
((ng*h/mL)/mg) 
Λz 
(1/h) 
CL/F 
(L/h) 
Vd/F 
(L) 
N 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CV % 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GM 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 103 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 75: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 80 mg Fasted Dose Group 
This table will repeat Table 74 for VT-1598 PK parameters in Plasma for the 80 mg Fasted Dose Group 
 
Table 76: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 160 mg Fasted Dose Group 
This table will repeat Table 74 for VT-1598 PK parameters in Plasma for the 160 mg Fasted Dose Group 
 
Table 77: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 160 mg Fed Dose Group 
This table will repeat Table 74 for VT-1598 PK parameters in Plasma for the 160 mg Fed Dose Group 
 
Table 78: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 320 mg Fasted Dose Group 
This table will repeat Table 74 for VT-1598 PK parameters in Plasma for the 320 mg Fasted Dose Group 
 
Table 79: 
Summary Statistics for VT-1598 PK Parameters in Plasma, 640 mg Fasted Dose Group 
This table will repeat Table 74 for VT-1598 PK parameters in Plasma for the 640 mg Fasted Dose Group 
 
Table 80: 
Summary Statistics for VT-11134 PK Parameters in Plasma by Dose Group 
This table will repeat Table 73 for VT-11134 PK parameters in plasma, by Dose Group 
 
Table 81: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 40 mg Fasted Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in plasma for the 40 mg Fasted Dose Group 
 
Table 82: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 80 mg Fasted Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in Plasma for the 80 mg Fasted Dose Group 
 
Table 83: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 160 mg Fasted Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in Plasma for the 160 mg Fasted Dose Group 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 104 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 84: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 160 mg Fed Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in Plasma for the 160 mg Fed Dose Group 
 
Table 85: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 320 mg Fasted Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in Plasma for the 320 mg Fasted Dose Group 
 
Table 86: 
Summary Statistics for VT-11134 PK Parameters in Plasma, 640 mg Fasted Dose Group 
This table will repeat Table 74 for VT-11134 PK parameters in Plasma for the 640 mg Fasted Dose Group 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 105 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 87: 
Summary Statistics for VT-1598 PK Parameters in Urine by Dose Group 
  
40 mg Fasted 
80 mg Fasted 
160 mg Fasted 
160 mg Fed 
320 mg Fasted 
640 mg Fasted 
Inpatient Period (0-72 h)a 
Aelast (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae%Dose (%) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
CLR (mL/min) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Nominal Collection Time Intervala 
Ae0-6 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae6-12 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae12-24 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae24-36 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae36-48 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae48-60 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae60-72 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Note: Values of Mean (Min, Max) are shown, except for CLR, for which values of GM (CV %) are shown.  
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 88: 
Summary Statistics for VT-1598 PK Parameters in Urine, 40 mg Fasted Dose Group 
 Statistics 
Inpatient Period (0-72 h)a 
Nominal Collection Time Intervala 
Aelast 
(mg) 
Ae%Dose 
(%) 
CLR 
(mL/min) 
Ae0-6 
(mg) 
Ae6-12 
(mg) 
Ae12-24 
(mg) 
Ae24-36 
(mg) 
Ae36-48 
(mg) 
Ae48-60 
(mg) 
Ae60-72 
(mg) 
N 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CV % 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GM 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 107 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 89: 
Summary Statistics for VT-1598 PK Parameters in Urine, 80 mg Fasted Dose Group 
This table will repeat Table 88 for VT-1598 PK parameters in Urine for the 80 mg Fasted Dose Group 
 
Table 90: 
Summary Statistics for VT-1598 PK Parameters in Urine, 160 mg Fasted Dose Group 
This table will repeat Table 88 for VT-1598 PK parameters in Urine for the 160 mg Fasted Dose Group 
 
Table 91: 
Summary Statistics for VT-1598 PK Parameters in Urine, 160 mg Fed Dose Group 
This table will repeat Table 88 for VT-1598 PK parameters in Urine for the 160 mg Fed Dose Group 
 
Table 92: 
Summary Statistics for VT-1598 PK Parameters in Urine, 320 mg Fasted Dose Group 
This table will repeat Table 88 for VT-1598 PK parameters in Urine for the 320 mg Fasted Dose Group 
 
Table 93: 
Summary Statistics for VT-1598 PK Parameters in Urine, 640 mg Fasted Dose Group 
This table will repeat Table 88 for VT-1598 PK parameters in Urine for the 640 mg Fasted Dose Group 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 108 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 94: 
Summary Statistics for VT-11134 PK Parameters in Urine by Dose Group 
  
40 mg Fasted 
80 mg Fasted 
160 mg Fasted 
160 mg Fed 
320 mg Fasted 
640 mg Fasted 
Inpatient Period (0-72 h)a 
Aelast (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
CLR (mL/min) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
x (x) 
Nominal Collection Time Intervala 
Ae0-6 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae6-12 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae12-24 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae24-36 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae36-48 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae48-60 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Ae60-72 (mg) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
x (xx, xx) 
Note: Values of Mean (Min, Max) are shown, except for CLR for which values of GM (CV %) are shown.  
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 109 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 95: 
Summary Statistics for VT-11134 PK Parameters in Urine, 40 mg Fasted Dose Group 
  
Inpatient Period (0-72 h) a 
Nominal Collection Time Intervala 
Statistics  
Aelast (mg) 
CLR (mL/min) 
Ae0-6 (mg) 
Ae6-12 (mg) 
Ae12-24 (mg) 
Ae24-36 (mg) 
Ae36-48 (mg) 
Ae48-60 (mg) 
Ae60-72 (mg) 
N 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Mean 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SD 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Min 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Max 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CV % 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GM 
x 
x 
x 
x 
x 
x 
x 
x 
X 
a Times are relative to time of dosing. 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 110 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 96: 
Summary Statistics for VT-11134 PK Parameters in Urine, 80 mg Fasted Dose Group 
This table will repeat Table 95 for VT-11134 PK parameters in Urine for the 80 mg Fasted Dose Group 
 
Table 97: 
Summary Statistics for VT-11134 PK Parameters in Urine, 160 mg Fasted Dose Group 
This table will repeat Table 95 for VT-11134 PK parameters in Urine for the 160 mg Fasted Dose Group 
 
Table 98: 
Summary Statistics for VT-11134 PK Parameters in Urine, 160 mg Fed Dose Group 
This table will repeat Table 95 for VT-11134 PK parameters in Urine for the 160 mg Fed Dose Group 
 
Table 99: 
Summary Statistics for VT-11134 PK Parameters in Urine, 320 mg Fasted Dose Group 
This table will repeat Table 95 for VT-11134 PK parameters in Urine for the 320 mg Fasted Dose Group 
 
Table 100: 
Summary Statistics for VT-11134 PK Parameters in Urine, 640 mg Fasted Dose Group 
This table will repeat Table 95 for VT-11134 PK parameters in Urine for the 640 mg Fasted Dose Group 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
- 111 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 101: 
Assessment of Dose Proportionality Among Fasted Dose Groups  
Statistic 
VT-1598 
VT-11134 
Cmax 
AUC0-last 
AUC0-inf 
Cmax 
AUC0-last 
AUC0-inf 
(ng/mL) 
(ng*h/mL) 
(ng*h/mL) 
(ng/mL) 
(ng*h/mL) 
(ng*h/mL) 
Lowest Dose Included (mg) 
x 
x 
x 
x 
x 
x 
Highest Dose Included (mg) 
x 
x 
x 
x 
x 
x 
ρ  
x 
x 
x 
x 
x 
x 
β-hat 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
Standard Error (β-hat) 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
ρ β-hat-1 90% CI 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
(x.xx, x.xx) 
Conclude parameter shows dose 
proportionality? 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Note: β-hat is an estimate obtained using the linear model log(Param) = α + dose × β, where Param is AUC0-last, AUC0-inf , or Cmax. Perfect dose 
proportionality is equivalent to β = 1. The value ρ is equivalent to the ratio of the highest dose included in the analysis divided by the lowest 
dose included in the analysis. Presence of dose proportionality is concluded when the 90% confidence interval for ρ β-hat-1 is contained within 
the interval (0.80,1.25). 
 


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Table 102: 
Comparison of Tmax between Fasted and Fed 160 mg Dose Groups 
[Implementation Note: Since fewer than 3 subjects in the PK Analysis Population were in both Cohort 3 and Cohort 6 then the Wilcoxon signed-rank test 
comparing Tmax (Paired) between the cohorts will not be conducted. The N, Estimate, and 90% CI cells should be “-“ and a footnote should be added to 
explain why they are missing. ] 
Parameter  
Estimand 
Subjects Included 
VT-1598 
VT-11134 
Na 
Estimate 
90% CIb 
Na 
Estimate 
90% CIb 
Tmax (Paired) 
Median of (160 mg Fed Tmax) - 
(160 mg Fasted Tmax) 
Subjects who received 160 mg of VT-1598  in both Cohort 3 (Fast) 
and Cohort 6 (Fed). 
x 
x 
(x, x) 
x 
x 
(x, x) 
Tmax (Independent) 
(160 mg Fed Tmax Median) - 
(160 mg Fasted Tmax Median) 
Any subject who received 160 mg of VT-1598 in either Cohort 3 
(Fast) or Cohort 6 (Fed) 
x 
x 
(x, x) 
x 
x 
(x, x) 
a N=Number of subjects with data used to compute Tmax. In the paired comparison, data was used from any subject in the PK Analysis Subset who received 160 mf VT-1598 under both a fasted and fed 
state. In the independent comparison, data was used from any subject in the PK Analysis Subset who received 160 mg VT-1598 under either a fasted or fed state, regardless of whether or not the 
subject participated in both study parts. 
b The 90% CI for subjects who receive VT-1598 and participated in both cohorts was calculated using Wilcoxon signed-rank test. The 90% CI for all subjects who received VT-1598 in either cohort 
was calculated using a Wilcoxon rank sum test.  
 


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Table 103: 
Comparison of Plasma PK Exposure Parameters between Fasted and Fed 160 mg Dose Groups – VT-1598 
Exposure Parameter  Comparison 
VT-1598 
VT-11134 
Na 
Estimate 
90% CIb 
Na 
Estimate 
90% CIb 
Cmax Ratio (Fed/Fast) 
x 
x 
(x, x) 
x 
x 
(x, x) 
AUC(0-last) Ratio (Fed/Fast) 
x 
x 
(x, x) 
x 
x 
(x, x) 
AUC(0-inf) Ratio (Fed/Fast) 
x 
x 
(x, x) 
x 
x 
(x, x) 
a N=Number of subjects with data used to compute the exposure parameters. Data was used from any subject in the PK Analysis Subset who received 160 mg VT-1598 under either a fasted or fed state, 
regardless of whether or not the subject participated in both study parts. BQL values were imputed as 0 if the sample was taken before the first measurable PK sample with a concentration above the 
LLOQ. BQL values were treated as missing otherwise. 
b 90% CI estimated using a mixed effects model for the geometric mean of each parameter by fasting status with a random subject effect. Individual parameter estimates were log transformed before 
inclusion in the model. 
 


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APPENDIX 2. FIGURE MOCK-UPS 
LIST OF FIGURES 
Figure 1: 
 Schematic of Study Design ......................................................................................120 
Figure 2: 
CONSORT Flow Diagram .......................................................................................121 
Figure 3: 
Proportion of Subjects with Related Adverse Events by MedDRA SOC and 
Maximum Severity – All Dose Groups ....................................................................122 
Figure 4: 
Number of Related Adverse Events by MedDRA SOC and Severity – All 
Dose Groups .............................................................................................................123 
Figure 5: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Albumin ............................................124 
Figure 6: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Glucose .............................................125 
Figure 7: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Blood Urea Nitrogen ........................125 
Figure 8: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Potassium ..........................................125 
Figure 9: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Calcium .............................................125 
Figure 10: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Sodium ..............................................125 
Figure 11: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Chloride ............................................125 
Figure 12: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Total Protein .....................................125 
Figure 13: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Creatinine ..........................................126 
Figure 14: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Triglycerides .....................................126 
Figure 15: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Total Cholesterol ..............................126 
Figure 16: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Low-Density Lipoprotein .................126 
Figure 17: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – High-Density Lipoprotein .................126 
Figure 18: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Total Carbon Dioxide .......................126 


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Figure 19: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Creatine Phosphokinase ....................126 
Figure 20: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Phosphorus ........................................127 
Figure 21: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Alkaline Phosphatase ........................127 
Figure 22: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Aspartate Aminotransferase .............127 
Figure 23: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Alanine Aminotransferase ................127 
Figure 24: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Total Bilirubin ..................................127 
Figure 25: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Direct Bilirubin .................................127 
Figure 26: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Magnesium .......................................127 
Figure 27: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Gamma-Glutamyl Transferase..........128 
Figure 28: Chemistry Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Serum Cortisol ..................................128 
Figure 29: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Hemoglobin ......................................129 
Figure 30: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Hematocrit ........................................129 
Figure 31: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Lymphocytes ....................................129 
Figure 32: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Neutrophils .......................................129 
Figure 33: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Monocytes ........................................129 
Figure 34: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Eosinophils .......................................129 
Figure 35: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Basophils ..........................................129 
Figure 36: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Platelet Count ...................................130 
Figure 37: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Red Blood Cell Count .......................130 


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Figure 38: Hematology Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – White Blood Cell Count ...................130 
Figure 39: Coagulation Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Activated Partial 
Thromboplastin Time ...............................................................................................131 
Figure 40: Coagulation Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Prothrombin Time .............................131 
Figure 41: Coagulation Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – International Normalized Ratio ........131 
Figure 42: Urinalysis Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – Specific Gravity ................................132 
Figure 43: Urinalysis Laboratory Results by Scheduled Visits: Change from Baseline 
by Parameter, Dose Group, and Timepoint – pH .....................................................132 
Figure 44: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 40 mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– 
Systolic Blood Pressure ............................................................................................133 
Figure 45: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– 
Systolic Blood Pressure ............................................................................................134 
Figure 46: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, Any Dose and Placebo Dose Groups– Systolic Blood Pressure ............135 
Figure 47: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 40 mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– 
Diastolic Blood Pressure ...........................................................................................136 
Figure 48: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– 
Diastolic Blood Pressure ...........................................................................................136 
Figure 49: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, Any Dose and Placebo Dose Groups– Diastolic Blood Pressure ..........136 
Figure 50: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 40 mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– 
Pulse ..........................................................................................................................136 
Figure 51: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 160 mg Fasted, SAD 160 mg Fed, and 640 mg Fasted Dose 
Groups – Pulse ..........................................................................................................136 
Figure 52: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, Any Dose and Placebo Dose Groups– Pulse .........................................136 


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Figure 53: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 40 mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– 
Respiratory Rate .......................................................................................................136 
Figure 54: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups – 
Respiratory Rate .......................................................................................................137 
Figure 55: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, Any Dose and Placebo Dose Groups– Respiratory Rate .......................137 
Figure 56: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 40 mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– 
Temperature ..............................................................................................................137 
Figure 57: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– 
Temperature ..............................................................................................................137 
Figure 58: Vital Signs by Scheduled Visits: Change from Baseline by Parameter and 
Timepoint, Any Dose and Placebo Dose Groups– Temperature ..............................137 
Figure 59: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group – PR Interval ..................................................................................................138 
Figure 60: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group – QRS Duration .............................................................................................139 
Figure 61: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group – QT Interval .................................................................................................139 
Figure 62: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group – QTcF  Interval ............................................................................................139 
Figure 63: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group – RR Interval .................................................................................................139 
Figure 64: ECG by Scheduled Visits: Change from Baseline by Parameter and Dose 
Group –Mean Ventricular Heart Rate .......................................................................139 
Figure 65: Individual VT-1598 Concentration in Plasma Profiles,  0 h to 72 h Post Dose 
– 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups .....................................140 
Figure 66: Individual VT-1598 Concentration in Plasma Profiles,  0 h to 72 h Post Dose 
– 160 mg Fasted and 160 mg Fed Dose Groups .......................................................141 
Figure 67: Individual VT-1598 Concentration in Plasma Profiles, All Timepoints Post 
Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups ...........................142 
Figure 68: Individual VT-1598 Concentration in Plasma Profiles, All Timepoints Post 
Dose – 160 mg Fasted and 160 mg Fed Dose Groups ..............................................143 
Figure 69: Individual VT-11134 Concentration in Plasma Profiles by Dose Group, 0 h 
to 72 h Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups .......144 


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Figure 70: Individual VT-11134 Concentration in Plasma Profiles by Dose Group, 0 h 
to 72 h Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups ..........................144 
Figure 71: Individual VT-11134 Concentration in Plasma Profiles by Dose Group, All 
Timepoints Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose 
Groups .......................................................................................................................144 
Figure 72: Individual VT-11134 Concentration in Plasma Profiles by Dose Group, All 
Timepoints Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups ...................144 
Figure 73: Individual Cumulative Amount of VT-1598 Excreted into Urine – 40 mg, 80 
mg, 320 mg, and 640 mg Fasted Dose Groups .........................................................145 
Figure 74: Individual Cumulative Amount of VT-1598 Excreted into Urine – 160 mg 
Fasted and 160 mg Fed Dose Groups .......................................................................146 
Figure 75: Individual Cumulative Amount of VT-11134 Excreted into Urine by Dose 
Group – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups .........................147 
Figure 76: Individual Cumulative Amount of VT-11134 Excreted into Urine by Dose 
Group – 160 mg Fasted and 160 mg Fed Dose Groups ............................................147 
Figure 77: Semi-Log Individual VT-1598 Concentration Profiles in Plasma, 0 h to 72 h 
Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups ....................148 
Figure 78: Semi-Log Individual VT-1598 Concentration Profiles in Plasma, 0 h to 72 h 
Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups ......................................149 
Figure 79: Semi-Log Individual VT-1598 Concentration Profiles in Plasma, All 
Timepoints –  40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups ................150 
Figure 80: Semi-Log Individual VT-1598 Concentration Profiles in Plasma, All 
Timepoints – 160 mg Fasted and 160 mg Fed Dose Groups ....................................151 
Figure 81: Semi-Log Individual VT-11134 Concentration Profiles in Plasma, 0 h to 72 
h Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups.................152 
Figure 82: Semi-Log Individual VT-11134 Concentration Profiles in Plasma, 0 h to 72 
h Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups ...................................152 
Figure 83: Semi-Log Individual VT-11134 Concentration Profiles in Plasma, All 
Timepoints Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose 
Groups .......................................................................................................................152 
Figure 84: Semi-Log Individual VT-11134 Concentration Profiles in Plasma, All 
Timepoints Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups ...................152 
Figure 85: Mean VT-1598 Concentration in Plasma Profiles by Dose Group – 0 h to 72 
h Post Dose ...............................................................................................................153 
Figure 86: Mean VT-1598 Concentration in Plasma Profiles by Dose Group – All 
Timepoints Post Dose ...............................................................................................154 
Figure 87: Mean VT-11134 Concentration in Plasma Profiles by Dose Group – 0 h to 
72 h Post Dose ..........................................................................................................155 


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Figure 88: Mean VT-11134 Concentration in Plasma Profiles by Dose Group – All 
Timepoints Post Dose ...............................................................................................155 
Figure 89: Mean Cumulative Amount of VT-1598 Excreted into Urine by Dose Group .........156 
Figure 90: Mean Cumulative Amount of VT-11134 Excreted into Urine by Dose Group .......157 
Figure 91: Mean Semi-Log VT-1598 Concentration in Plasma Profiles by Dose Group 
– 0 h to 72 h Post Dose .............................................................................................158 
Figure 92: Mean Semi-Log VT-1598 Concentration in Plasma Profiles by Dose Group 
– All Timepoints Post Dose ......................................................................................159 
Figure 93: Mean Semi-Log VT-11134 Concentration in Plasma Profiles, by Dose 
Group – 0 h to 72 h Post Dose ..................................................................................160 
Figure 94: Mean Semi-Log VT-11134 Concentration in Plasma Profiles, by Dose 
Group – All Timepoints Post Dose ...........................................................................160 
Figure 95: Mean Concentration in Plasma by Analyte – 40 mg and 80 mg Fasted Dose 
Groups .......................................................................................................................161 
Figure 96: Mean Concentration in Plasma by Analyte – 160 mg Fasted and Fed Dose 
Groups .......................................................................................................................162 
Figure 97: Mean Concentration in Plasma by Analyte – 320 mg and 640 mg Fasted 
Dose Groups .............................................................................................................162 
Figure 98: Mean of Cumulative Amount Excreted into Urine by Analyte – 40 mg and 
80 mg Fasted Dose Groups .......................................................................................163 
Figure 99: Mean of Cumulative Amount Excreted into Urine by Analyte – 160 mg 
Fasted and Fed Dose Groups ....................................................................................164 
Figure 100: Mean of Cumulative Amount Excreted into Urine by Analyte – 320 and 640 
mg Fasted Dose Groups ............................................................................................164 
Figure 101: Dose Proportionality, Fasted Cmax, VT-1598 in Plasma............................................165 
Figure 102: Dose Proportionality, Fasted AUC0-last, VT-1598 in Plasma ....................................166 
Figure 103: Dose Proportionality, Fasted AUC0-inf, VT-1598 in Plasma .....................................166 
Figure 104: Dose Proportionality, Fasted Cmax, VT-11134 in Plasma..........................................166 
Figure 105: Dose Proportionality, Fasted AUC0-last, VT-11134 in Plasma ..................................166 
Figure 106: Dose Proportionality, Fasted AUC0-inf, VT-11134 in Plasma ...................................166 


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Figure 1: 
 Schematic of Study Design 
PK blood sampling (all subjects)
pre-dose; post-dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 14hr
PK urine sampling (all subjects):
pre-dose; post-dose 0-6, 6-12, 12-24 hr
Day 21 (+/- 2 days)
PE, vitals, ECG, clin labs
480hr PK blood samples
Days 7 & 14 outpatient (+/- 1 day)
vitals, clin labs
144 & 312 hour PK blood samples
Day 4
Physical exam, vitals, ECG, Clin labs
72 hr PK blood & 60-72 hr PK urine samples
Discharge from CRU
Days 2 & 3 (confined)
Vitals, Conmeds
 24, 36, 48, 60 hr PK blood samples & 24-36, 36-48, 48-60 hr PK urine samples
Day 1
Study product administration (per cohort dose regimen)
PK blood sampling through 14hr post-dose- PK urine sampling up to 24 hr post-dose (time points below)
Day -1
Enrollment and baseline assessments
Admitted and confined to CRU
Randomization
Up to Day -28
Screening


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10.1 
Disposition of Subjects 
Figure 2: 
CONSORT Flow Diagram 
[Implementation Note: CONSORT flow diagram will show numbers of subjects screened and enrolled. By 
Dose Group it will also display the number randomized, treated, and completed the study. Additionally, the 
diagram will show the number of subjects excluded from analysis populations by reason for exclusion.] 
Placeholder for Figure 2 – CONSORT Flow Diagram 
 


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14.3.1.2 Unsolicited Adverse Events 
Figure 3: 
Proportion of Subjects with Related Adverse Events by MedDRA SOC and Maximum 
Severity – All Dose Groups 
[Implementation Note: This figure includes serious and non-serious unsolicited adverse events related to the 
study product. Note that this figure will present the number of subjects with each type of SOC. A subject will 
only be counted once for the same SOC for the maximum severity  reported. Each figure panel will show 
counts for all SOCs observed in the Any Dose Group during the study (as a related AE). If the number of 
SOCs is too large to fit using 2 rows of panels, then the figure can be split with one row of 3 panels in each 
figure.  
Subjects who received VT-1598 in both Cohorts 3 and 6 will be summarized separately for each dose 
received in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 and 6 will be 
summarized separately for each dose received in the Placebo Dose Group. 
Order SOCs alphabetically.] 


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Figure 4: 
Number of Related Adverse Events by MedDRA SOC and Severity – All Dose Groups  
[Implementation Note: This figure includes serious and non-serious unsolicited adverse events related to the 
study product. Note that this figure will present the total counts of adverse events, a subject may contribute 
more than one count for the same type of adverse event. Each figure panel will show counts for all SOCs 
observed in any Dose Group during the study (as a related AE). If the number of SOCs is too large to fit using 
2 rows of panels, then the figure can be split with one row of 3 panels in each figure.  
Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately for each dose received in 
the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 and 6 will be included 
separately for each dose received in the Placebo Dose Group. 
Order SOCs alphabetically.] 
 
 


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14.3.5 
Displays of Laboratory Results 
14.3.5.1  
Chemistry Results 
Figure 5: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Albumin 
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dose received in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dose received in the Placebo Dose Group.] 
 


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Figure 6: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Glucose 
This figure will repeat Figure 5 for Glucose 
 
Figure 7: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Blood Urea Nitrogen 
This figure will repeat Figure 5 for Blood Urea Nitrogen 
 
Figure 8: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Potassium 
This figure will repeat Figure 5 for Potassium 
 
Figure 9: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Calcium 
This figure will repeat Figure 5 for Calcium 
 
Figure 10: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Sodium 
This figure will repeat Figure 5 for Sodium 
 
Figure 11: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Chloride 
This figure will repeat Figure 5 for Chloride 
 
Figure 12: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Total Protein 
This figure will repeat Figure 5 for Total Protein 
 


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Figure 13: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Creatinine 
This figure will repeat Figure 5 for Creatinine 
 
Figure 14: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Triglycerides 
This figure will repeat Figure 5 for Triglycerides 
 
Figure 15: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Total Cholesterol 
This figure will repeat Figure 5 for Total Cholesterol 
 
Figure 16: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Low-Density Lipoprotein 
This figure will repeat Figure 5 for Low-Density Lipoprotein 
 
Figure 17: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – High-Density Lipoprotein  
This figure will repeat Figure 5 for High-Density Lipoprotein 
 
Figure 18: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Total Carbon Dioxide 
This figure will repeat Figure 5 for Total Carbon Dioxide 
 
Figure 19: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Creatine Phosphokinase 
This figure will repeat Figure 5 for Creatine Phosphokinase 
 


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Figure 20: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Phosphorus 
This figure will repeat Figure 5 for Phosphorus 
Figure 21: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Alkaline Phosphatase 
This figure will repeat Figure 5 for Alkaline Phosphatase 
Figure 22: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Aspartate Aminotransferase 
This figure will repeat Figure 5 for Aspartate Aminotransferase 
Figure 23: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Alanine Aminotransferase 
This figure will repeat Figure 5 for Alanine Aminotransferase 
Figure 24: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Total Bilirubin 
This figure will repeat Figure 5 for Total Bilirubin 
Figure 25: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Direct Bilirubin 
This figure will repeat Figure 5 for Direct Bilirubin 
Figure 26: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Magnesium 
This figure will repeat Figure 5 for Magnesium 


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Figure 27: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Gamma-Glutamyl Transferase 
This figure will repeat Figure 5 for Gamma-Glutamyl Transferase 
 
Figure 28: 
Chemistry Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Serum Cortisol 
This figure will repeat Figure 5 for Serum Cortisol 
 


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14.3.5.2  
Hematology Results 
Figure 29: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Hemoglobin 
This figure will repeat Figure 5 for Hemoglobin 
 
Figure 30: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Hematocrit 
This figure will repeat Figure 5 for Hematocrit 
 
Figure 31: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Lymphocytes 
This figure will repeat Figure 5 for Lymphocytes 
 
Figure 32: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Neutrophils 
This figure will repeat Figure 5 for Neutrophils 
 
Figure 33: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Monocytes 
This figure will repeat Figure 5 for Monocytes 
 
Figure 34: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Eosinophils 
This figure will repeat Figure 5 for Eosinophils 
 
Figure 35: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Basophils 
This figure will repeat Figure 5 for Basophils 


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Figure 36: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Platelet Count 
This figure will repeat Figure 5 for Platelets  
 
Figure 37: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Red Blood Cell Count 
This figure will repeat Figure 5 for Red Blood Cell Count 
 
Figure 38: 
Hematology Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – White Blood Cell Count 
This figure will repeat Figure 5 for White Blood Cell Count 
 
 


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14.3.5.3  
Coagulation Results 
Figure 39: 
Coagulation Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Activated Partial Thromboplastin Time 
This figure will repeat Figure 5 for Activated Partial Thromboplastin Time 
 
Figure 40: 
Coagulation Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – Prothrombin Time 
This figure will repeat Figure 5 for Prothrombin Time 
 
Figure 41: 
Coagulation Laboratory Results by Scheduled Visits: Change from Baseline by 
Parameter, Dose Group, and Timepoint – International Normalized Ratio 
This figure will repeat Figure 5 for International Normalized Ratio 
 
 


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14.3.5.4  
Urinalysis Results 
Figure 42: 
Urinalysis Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – Specific Gravity 
This figure will repeat Figure 5 for Specific Gravity 
 
Figure 43: 
Urinalysis Laboratory Results by Scheduled Visits: Change from Baseline by Parameter, 
Dose Group, and Timepoint – pH  
This figure will repeat Figure 5 for pH 
 
 


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14.3.5.6 
Displays of Vital Signs 
Figure 44: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 40 
mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– Systolic Blood Pressure  
[Implementation note: the presented order of dose groups in this figure contradicts the specified order of 
section 3.3.2 due to constraints on the number of graphs that can be presented per page. The 160 mg 
Fasted and Fed and the Any Dose/Placebo graphs are kept together for ease of viewing.] 


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Figure 45: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 160 
mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– Systolic Blood Pressure  
[Implementation note: the presented order of dose groups in this figure contradicts the specified order of 
section 3.3.2 due to constraints on the number of graphs that can be presented per page. The 160 mg Fasted 
and Fed and the Any Dose/Placebo graphs are kept together for ease of viewing.] 
  
 


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Figure 46: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, Any 
Dose and Placebo Dose Groups– Systolic Blood Pressure  
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dose received in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dose received in the Placebo Dose Group. The presented order of 
dose groups in this figure contradicts the specified order of section 3.3.2 due to constraints on the number of 
graphs that can be presented per page. The 160 mg Fasted and Fed and the Any Dose/Placebo graphs are kept 
together for ease of viewing.] 
 
 


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Figure 47: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 40 
mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– Diastolic Blood Pressure  
This figure will repeat Figure 43 for Diastolic Blood Pressure 
 
Figure 48: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 160 
mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– Diastolic Blood Pressure  
This figure will repeat Figure 44 for Diastolic Blood Pressure in 160 mg Fasted, 160 mg Fed, and 640 mg 
Fasted Dose Groups 
 
Figure 49: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, Any 
Dose and Placebo Dose Groups– Diastolic Blood Pressure  
This figure will repeat Figure 45 for Diastolic Blood Pressure in the Any Dose Group and Placebo Dose 
Group 
 
Figure 50: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 40 
mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– Pulse 
This figure will repeat Figure 43 for Pulse 
 
Figure 51: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 160 
mg Fasted, SAD 160 mg Fed, and 640 mg Fasted Dose Groups – Pulse  
This figure will repeat Figure 44 for Pulse in 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups 
 
Figure 52: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, Any 
Dose and Placebo Dose Groups– Pulse  
This figure will repeat Figure 45 for Pulse in the Any Dose Group and Placebo Dose Group 
 
Figure 53: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 40 
mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– Respiratory Rate 
This figure will repeat Figure 43 for Respiratory Rate 
 


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Figure 54: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 160 
mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups – Respiratory Rate  
This figure will repeat Figure 44 for Respiratory Rate in 160 mg Fasted, 160 mg Fed, and 640 mg Fasted 
Dose Groups 
 
Figure 55: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, Any 
Dose and Placebo Dose Groups– Respiratory Rate  
This figure will repeat Figure 45 for Respiratory Rate in the Any Dose Group and Placebo Dose Group 
 
Figure 56: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 40 
mg Fasted, 80 mg Fasted, and 320 mg Fasted Dose Groups– Temperature 
This figure will repeat Figure 43 for Temperature 
 
Figure 57: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, 160 
mg Fasted, 160 mg Fed, and 640 mg Fasted Dose Groups– Temperature  
This figure will repeat Figure 44 for Temperature in 160 mg Fasted, 160 mg Fed, and 640 mg Fasted Dose 
Groups 
 
Figure 58: 
Vital Signs by Scheduled Visits: Change from Baseline by Parameter and Timepoint, Any 
Dose and Placebo Dose Groups– Temperature  
This figure will repeat Figure 45 for Temperature in the Any Dose Group and Placebo Dose Group 
 


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14.3.5.7  
Displays of ECG Measurements 
Figure 59: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group – PR 
Interval  
[Implementation Note: Subjects who received VT-1598 in both Cohorts 3 and 6 will be included separately 
for each dose received in the Any Dose Group. Similarly, subjects who received placebo in both Cohorts 3 
and 6 will be included separately for each dose received in the Placebo Dose Group.] 


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Figure 60: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group – QRS 
Duration  
This figure will repeat Figure 58 for QRS Duration 
 
Figure 61: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group – QT 
Interval  
This figure will repeat Figure 58 for QT Interval  
 
Figure 62: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group – QTcF  
Interval  
This figure will repeat Figure 58 for QTcF Interval 
 
Figure 63: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group – RR 
Interval  
This figure will repeat Figure 58 for RR Interval 
 
Figure 64: 
ECG by Scheduled Visits: Change from Baseline by Parameter and Dose Group –Mean 
Ventricular Heart Rate  
This figure will repeat Figure 58 for Mean Ventricular Heart Rate 
 
 


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14.3.5.6  
Displays of PK Results and Parameters  
Figure 65: 
Individual VT-1598 Concentration in Plasma Profiles,  0 h to 72 h Post Dose – 40 mg, 80 
mg, 320 mg, and 640 mg Fasted Dose Groups 


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Figure 66: 
Individual VT-1598 Concentration in Plasma Profiles,  0 h to 72 h Post Dose – 160 mg 
Fasted and 160 mg Fed Dose Groups 
 
 


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Figure 67: 
Individual VT-1598 Concentration in Plasma Profiles, All Timepoints Post Dose – 40 mg, 
80 mg, 320 mg, and 640 mg Fasted Dose Groups 
 
 


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Figure 68: 
Individual VT-1598 Concentration in Plasma Profiles, All Timepoints Post Dose – 160 mg 
Fasted and 160 mg Fed Dose Groups 
 
 


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Figure 69: 
Individual VT-11134 Concentration in Plasma Profiles by Dose Group, 0 h to 72 h Post 
Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
This figure will repeat Figure 64 for VT-11134 in Plasma 
 
Figure 70: 
Individual VT-11134 Concentration in Plasma Profiles by Dose Group, 0 h to 72 h Post 
Dose – 160 mg Fasted and 160 mg Fed Dose Groups 
This figure will repeat Figure 65 for VT-11134 in Plasma 
 
Figure 71: 
Individual VT-11134 Concentration in Plasma Profiles by Dose Group, All Timepoints 
Post Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
This figure will repeat Figure 66 for VT-11134 in Plasma 
 
Figure 72: 
Individual VT-11134 Concentration in Plasma Profiles by Dose Group, All Timepoints 
Post Dose – 160 mg Fasted and 160 mg Fed Dose Groups 
This figure will repeat Figure 67 for VT-11134 in Plasma 


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Figure 73: 
Individual Cumulative Amount of VT-1598 Excreted into Urine – 40 mg, 80 mg, 320 mg, 
and 640 mg Fasted Dose Groups 
 
 


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Figure 74: 
Individual Cumulative Amount of VT-1598 Excreted into Urine – 160 mg Fasted and 160 
mg Fed Dose Groups 
 
 


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Figure 75: 
Individual Cumulative Amount of VT-11134 Excreted into Urine by Dose Group – 40 
mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
This figure will repeat Figure 72 for VT-11134 in Urine 
 
Figure 76: 
Individual Cumulative Amount of VT-11134 Excreted into Urine by Dose Group – 160 
mg Fasted and 160 mg Fed Dose Groups 
This figure will repeat Figure 73 for VT-11134 in Urine 


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Figure 77: 
Semi-Log Individual VT-1598 Concentration Profiles in Plasma, 0 h to 72 h Post Dose – 
40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
 
 


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Figure 78: 
Semi-Log Individual VT-1598 Concentration Profiles in Plasma, 0 h to 72 h Post Dose – 
160 mg Fasted and 160 mg Fed Dose Groups 
 
 


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Figure 79: 
Semi-Log Individual VT-1598 Concentration Profiles in Plasma, All Timepoints –  40 mg, 
80 mg, 320 mg, and 640 mg Fasted Dose Groups 
 
 


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Figure 80: 
Semi-Log Individual VT-1598 Concentration Profiles in Plasma, All Timepoints – 160 mg 
Fasted and 160 mg Fed Dose Groups 
 
 


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Figure 81: 
Semi-Log Individual VT-11134 Concentration Profiles in Plasma, 0 h to 72 h Post Dose – 
40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
This figure will repeat Figure 76 for VT-11134 in plasma 
 
Figure 82: 
Semi-Log Individual VT-11134 Concentration Profiles in Plasma, 0 h to 72 h Post Dose – 
160 mg Fasted and 160 mg Fed Dose Groups 
This figure will repeat Figure 77 for VT-11134 in plasma 
 
Figure 83: 
Semi-Log Individual VT-11134 Concentration Profiles in Plasma, All Timepoints Post 
Dose – 40 mg, 80 mg, 320 mg, and 640 mg Fasted Dose Groups 
This figure will repeat Figure 78 for VT-11134 in plasma 
 
Figure 84: 
Semi-Log Individual VT-11134 Concentration Profiles in Plasma, All Timepoints Post 
Dose – 160 mg Fasted and 160 mg Fed Dose Groups 
This figure will repeat Figure 79 for VT-11134 in plasma 


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Figure 85: 
Mean VT-1598 Concentration in Plasma Profiles by Dose Group – 0 h to 72 h Post Dose 
 
 


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Figure 86: 
Mean VT-1598 Concentration in Plasma Profiles by Dose Group – All Timepoints Post 
Dose 
 
 
 


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Figure 87: 
Mean VT-11134 Concentration in Plasma Profiles by Dose Group – 0 h to 72 h Post Dose 
This figure will repeat Figure 84 for VT-11134 in plasma 
 
Figure 88: 
Mean VT-11134 Concentration in Plasma Profiles by Dose Group – All Timepoints Post 
Dose 
This figure will repeat Figure 85 for VT-11134 in plasma 


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Figure 89: 
Mean Cumulative Amount of VT-1598 Excreted into Urine by Dose Group 


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Figure 90: 
Mean Cumulative Amount of VT-11134 Excreted into Urine by Dose Group 
This figure will repeat Figure 88 for VT-11134 in urine 
 


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Figure 91: 
Mean Semi-Log VT-1598 Concentration in Plasma Profiles by Dose Group – 0 h to 72 h 
Post Dose 
 
 


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Figure 92: 
Mean Semi-Log VT-1598 Concentration in Plasma Profiles by Dose Group – All 
Timepoints Post Dose 
 
 


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Figure 93: 
Mean Semi-Log VT-11134 Concentration in Plasma Profiles, by Dose Group – 0 h to 72 h 
Post Dose 
This figure will repeat Figure 90 for VT-11134 in plasma 
 
Figure 94: 
Mean Semi-Log VT-11134 Concentration in Plasma Profiles, by Dose Group – All 
Timepoints Post Dose 
This figure will repeat Figure 91 for VT-11134 in plasma 
 


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Figure 95: 
Mean Concentration in Plasma by Analyte – 40 mg and 80 mg Fasted Dose Groups 
 
 


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Figure 96: 
Mean Concentration in Plasma by Analyte – 160 mg Fasted and Fed Dose Groups 
This figure will repeat Figure 94 for the 160 mg Fasted and Fed Dose Groups 
 
Figure 97: 
Mean Concentration in Plasma by Analyte – 320 mg and 640 mg Fasted Dose Groups 
This figure will repeat Figure 94 for the 320 and 640 mg Dose Groups 


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Figure 98: 
Mean of Cumulative Amount Excreted into Urine by Analyte – 40 mg and 80 mg Fasted 
Dose Groups 
  
 


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Figure 99: 
Mean of Cumulative Amount Excreted into Urine by Analyte – 160 mg Fasted and Fed 
Dose Groups 
This figure will repeat Figure 97 for the 160 mg Fasted and Fed Dose Groups 
 
Figure 100: 
Mean of Cumulative Amount Excreted into Urine by Analyte – 320 and 640 mg Fasted 
Dose Groups 
This figure will repeat Figure 97 for the 320 mg and 640 mg Fasted Dose Groups 


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Figure 101: 
Dose Proportionality, Fasted Cmax, VT-1598 in Plasma 
 
 


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Figure 102: 
Dose Proportionality, Fasted AUC0-last, VT-1598 in Plasma  
This figure will repeat Figure 100 from for AUC0-last for VT-1598 in plasma 
 
Figure 103: 
Dose Proportionality, Fasted AUC0-inf, VT-1598 in Plasma 
This figure will repeat Figure 100 from for AUC0-inf for VT-1598 in plasma 
 
Figure 104: 
Dose Proportionality, Fasted Cmax, VT-11134 in Plasma 
This figure will repeat Figure 100 from for Cmax for VT-11134 in plasma 
 
Figure 105: 
Dose Proportionality, Fasted AUC0-last, VT-11134 in Plasma  
This figure will repeat Figure 100 from for AUC0-last for VT-11134 in plasma 
 
Figure 106: 
Dose Proportionality, Fasted AUC0-inf, VT-11134 in Plasma  
This figure will repeat Figure 100 from for AUC0-inf for VT-11134 in plasma 
 


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APPENDIX 3. LISTINGS MOCK-UPS 
LISTINGS 
Listing 1: 16.1.6: Listing of Subjects Receiving Investigational Product .................................169 
Listing 2: 16.2.1: Early Terminations or Discontinued Subjects ..............................................170 
Listing 3: 16.2.2.1: Subject-Specific Protocol Deviations ........................................................171 
Listing 4: 16.2.2.2: Non-Subject-Specific Protocol Deviations ................................................172 
Listing 5: 16.2.3: Subjects Excluded from Analysis Populations .............................................173 
Listing 6: 16.2.4.1: Demographic Data .....................................................................................174 
Listing 7: 16.2.4.2: Pre-Existing and Concurrent Medical Conditions .....................................175 
Listing 8: Prior Medications ......................................................................................................176 
Listing 9: 16.2.10: Concomitant Medications ...........................................................................177 
Listing 10: 16.2.5: Compliance Data ..........................................................................................178 
Listing 11: 16.2.7.3: Unsolicited Adverse Events .......................................................................179 
Listing 12: 16.2.8.1: Clinical Laboratory Results – Chemistry ..................................................180 
Listing 13: 16.2.8.2: Clinical Laboratory Results – Hematology ...............................................181 
Listing 14: 16.2.8.3: Clinical Laboratory Results – Coagulation ...............................................182 
Listing 15: 16.2.8.3: Clinical Laboratory Results – Urinalysis...................................................183 
Listing 16: 16.2.9.1: Screening Laboratory Results – Serology .................................................184 
Listing 17: 16.2.9.1: Screening Laboratory Results – Urine Toxicology ...................................185 
Listing 18: 16.2.9.1: Screening Laboratory Results – Serum hCG and FSH Tests ....................186 
Listing 19: 16.2.9.1: Vital Signs .................................................................................................187 
Listing 20: 16.2.9.2: Abnormal Physical Exam Findings ...........................................................188 
Listing 21: 16.2.9.1: Listing of ECG Interval Measurements .....................................................189 
Listing 22: 16.2.9.1: Listing of ECG Overall Interpretation and Comments ..............................190 
Listing 23: 16.2.9.1: Listing of ECG Findings............................................................................191 
Listing 24: 16.2.11.1: Pregnancy Reports – Maternal Information ............................................192 
Listing 25: 16.2.11.2: Pregnancy Reports – Gravida and Para ...................................................193 
Listing 26: 16.2.11.3: Pregnancy Reports – Live Birth Outcomes .............................................194 
Listing 27: 16.2.11.4: Pregnancy Reports – Still Birth Outcomes ..............................................195 
Listing 28: 16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic 
Abortion Outcomes ...................................................................................................196 


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Listing 29: 16.2.11.6: Birth Control Listing ...............................................................................197 
Listing 30: 16.2.10: Subject Level VT-1598 and VT-11134 Concentrations – Plasma .............198 
Listing 31: 16.2.10: Subject Level VT-1598 and VT-11134 Concentrations – Urine ................199 
Listing 32: Subject Specific VT-1598 Plasma PK Parameters ...................................................200 
Listing 33: Subject Specific VT-11134 Plasma PK Parameters .................................................200 
Listing 34: Subject Specific VT-1598 Urine Inpatient Period PK Parameters ...........................201 
Listing 35: Subject Specific VT-1598 Urine Nominal Collection Time Interval PK 
Parameters .................................................................................................................202 
Listing 36: Subject Specific VT-11134 Urine Inpatient Period PK Parameters .........................202 
Listing 37: Subject Specific VT-11134 Urine Nominal Collection Time Interval PK 
Parameters .................................................................................................................202 
 


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Listing 1: 
16.1.6: Listing of Subjects Receiving Investigational Product 
(not included in SAP, but this is a placeholder for the CSR)  
 


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2: 
16.2.1: Early Terminations or Discontinued Subjects 
[Implementation Note: Category will either be “Early Termination” or “Treatment Discontinuation”. In the “Reason” column, concatenate any “specify” 
fields, including AE number and DV number.  
Sort order: Dose Group, Subject ID, Category (in the case that a subject both terminates early and discontinues treatment).] 
Dose Group 
Subject ID 
Category 
Reason for Early Termination or Treatment Discontinuation 
Study Day 
40 mg Fasted 
PH2.00123 
Early Termination 
Lost to Follow-up 
7 
 
 
 
 
 
 
 


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16.2.2 Protocol Deviations 
Listing 3: 
16.2.2.1: Subject-Specific Protocol Deviations 
[Implementation Note: In the “Deviation” column, concatenate any and all “specify” fields (including visit number, etc.). If  “Reason for Deviation is 
“Other,” concatenate the “specify” fields, separated by a colon, e.g., “Other: Subject refusal.” If deviation resulted in AE or subject termination, or 
affected product stability, indicate which of those events occurred in the listing row since those 3 columns were concatenated. 
Review the site comments carefully. Replace any occurrences of the PATID in the comments with the USUBJID.  
Sort order: Dose Group, Subject ID, DV Number.] 
Dose 
Group 
Subject 
ID 
DV 
Number 
Deviation 
Deviation 
Category 
Study 
Day 
Reason for 
Deviation 
Deviation Resulted in AE or Subject 
Termination, or Affected Product Stability? 
Deviation Resolution 
Comments 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
 
  
 
 


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Listing 4: 
16.2.2.2: Non-Subject-Specific Protocol Deviations 
[Implementation Note: In the “Deviation” column, concatenate any and all “specify” fields (including visit number, etc.). If “Reason for Deviation” is 
“Other,” concatenate “specify” field, separate by a colon, e.g., “Other: Subject refusal.”  
Review the site comments carefully. Replace any occurrences of the PATID in the comments with the USUBJID.  
Sort order: Start Date, Deviation.] 
Start Date  
Deviation 
End Date 
Reason for 
Deviation 
Deviation Resulted in 
Subject Termination? 
Deviation Affected 
Product Stability? Deviation Category 
Deviation Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.3 Subjects Excluded from the Efficacy Analysis 
Listing 5: 
16.2.3: Subjects Excluded from Analysis Populations 
[Implementation Note: This data in this listing should be congruent with the “Analysis Populations by Dose Group” table. If a subject was not excluded 
from any analysis population, the subject will not appear in the listing. If the subject was excluded from multiple analysis populations, they will have one 
row per analysis population excluded from in the listing. 
If no specifications are required for a reason for exclusion, then exclude the last column “Reason Subject Excluded Specification”. 
Sort order: Dose Group, Subject ID, Analysis from which Subject is Excluded (order: Safety, PK Analysis Population, PK Analysis Subset).] 
Dose Group 
Subject ID 
Analysis from which Subject is Excluded 
Results Available? 
Reason Subject Excluded 
Reason Subject Excluded Specification 
40 mg Fasted 
PH2.00123 
PK Analysis Subset 
Yes 
Has protocol deviations that 
potentially impact PK. 
Subject consumed food 1 hour prior to dosing. 
 
 
 
 
 
 
Note: "Yes" in the "Results Available" column indicates that available data were removed from the analysis. "No" indicates that no data were available for inclusion in the analysis. 
 
 


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16.2.4 Demographic Data 
Listing 6: 
16.2.4.1: Demographic Data 
[Implementation Note: If a subject is multi-racial, in “Race” column, note “Multiple: (list races, separated by a comma).” 
Sort order: Dose Group, Subject ID.] 
Dose Group 
Subject ID 
Sex 
Age at Enrollment (years) 
Ethnicity 
Race 
Weight at Screening (kg) 
Height at Screening (cm) 
BMI at Screening (kg/m2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 7: 
16.2.4.2: Pre-Existing and Concurrent Medical Conditions 
[Implementation Note: “Condition Start Day” and “Condition End Day” are relative to enrollment (which is Day 1, day before enrollment is  
Day -1). Rather than use exact study days, categorize as follows: 
• 5 years prior to enrollment 
• 1-5 years prior to enrollment 
• 1-12 months prior to enrollment 
• Within 1 month of enrollment 
• During study 
• If ongoing, display “Ongoing” in the “Condition End Day” column 
It may be appropriate to add another category, based on exclusion criteria that restrict conditions within a particular time period (e.g., within 3 years prior 
to enrollment). In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-identification.  
Sort order: Dose Group, Subject ID, MH Number.] 
Dose Group 
 Subject ID 
MH Number 
Medical History Term 
MedDRA System Organ Class 
MedDRA Preferred Term 
Condition Start Day 
Condition End Day 
40 mg Fasted 
PHU.00123 
1 
NUT ALLERGY 
IMMUNE SYSTEM DISORDERS 
FOOD ALLERGY 
>5 years prior to enrollment 
Ongoing 
 
 
 
 
 
 
 
 
 
 


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16.2.10 Concomitant Medications 
Listing 8: 
Prior Medications 
[Implementation Note: Include prior medications (medications with an end date prior to dosing) only. If the medication was taken for a Medical History 
condition, then include the MH description and the MH number in parentheses in the “Taken for a condition on the Medical History” column. If the start 
date is more than 30 days before enrollment, then categorize as follows:  
• 5 years prior to enrollment 
• 1-5 years prior to enrollment 
• 1-12 months prior to enrollment 
Sort order: Dose Group, Subject ID, and CM Number]. 
Dose 
Group 
Subject ID 
CM 
Number 
Medication 
Medication 
Start Day 
Medication 
End Day 
Indication 
Taken for a condition on Medical 
History? (MH Description; MH Number) 
ATC Level 1  
(ATC Level 2) 
40 mg 
Fasted 
PHU.00123 
001 
BENADRYL 
1-12 months 
prior to 
enrollment 
1-12 months 
prior to 
enrollment 
ITCHING 
No 
DERMATOLOGICALS (ANTIPRURITICS, 
INCL. ANTIHISTAMINES, ANESTHETICS, 
ETC.) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 


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Listing 9: 
16.2.10: Concomitant Medications 
[Implementation Note: “Medication Start Day” and “Medication End Day” are relative to enrollment (which is Day 1, day before enrollment is Day -1). 
For medication start dates that are > 30 days prior to enrollment, rather than use exact study days, categorize as follows: 
5 years prior to enrollment 
1-5 years prior to enrollment 
1-12 months prior to enrollment 
If ongoing, display “Ongoing” in the “Medication End Day” column. If taken for an AE or MH, display “Yes” with the AE or MH description and 
number in parentheses, e.g., “Yes (AE/MH Description; 007)”. In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-
identification.  
Sort order: Dose Group, Subject ID, and CM Number.] 
Dose 
Group Subject ID 
CM 
Number 
Medication 
Medication 
Start Day 
Medication 
End Day 
Indication 
Taken for an AE? 
(AE Description; Number) 
Taken for a condition on Medical History? 
(MH Description; Number) 
ATC Level 1  
(ATC Level 2) 
40 mg 
Fasted 
PHU.00123 
001 
BENADRYL 
2 
2 
ITCHING 
Yes (MACULAR RASH; 
001) 
No 
DERMATOLOGICALS 
(ANTIPRURITICS, 
INCL. 
ANTIHISTAMINES, 
ANESTHETICS, ETC.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.5 Compliance and/or Drug Concentration Data (if available) 
Listing 10: 
16.2.5: Compliance Data 
[Implementation Note: If not dosed according to protocol, details will be given in the Comments column (manually written, not programmed). If dose is 
not applicable for the subject, the date and time columns for those doses will be N/A. For planned doses that did not occur, the date and time columns for 
those doses will be “not dosed.” 
Sort Order: Dose Group, Subject ID 
Dose Group 
Subject ID 
Dosed According to Protocol? 
Dose Date 
Dose Time 
Vomited After Receiving Study Product? 
Comments 
40 mg Fasted 
PHU.0123 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
  
… 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 


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16.2.6 Adverse Events 
Listing 11: 
16.2.7.3: Unsolicited Adverse Events 
[Implementation Note: If the event is ongoing (no stop date), indicate “ongoing” in the duration column. In the “Relationship to Study Treatment 
(Alternate Etiology)” column, merge the data fields for relationship to study treatment and alternate etiology, separated by a colon. This listing includes 
all unsolicited adverse events.  
Sort Order: Dose Group, Subject ID, AE Number.] 
Adverse 
Event 
MedDRA 
System Organ 
Class 
MedDRA 
Higher Level 
Group Term 
MedDRA 
Preferred Term 
Number 
of Days 
Post Dose 
Duration 
of AE in 
Days 
Severity 
SAE? 
Relationship to 
Study Treatment 
(Alternate Etiology) 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Dose Group: , Subject ID: , AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
Comments: 
Dose Group: , Subject ID: , AE Number:  
  
  
  
  
  
  
  
  
  
  
  
  
Comments:  
 
 


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16.2.7 Individual Laboratory Measurements 
Listing 12: 
16.2.8.1: Clinical Laboratory Results – Chemistry 
[Implementation Note: These listings (for hematology, chemistry, coagulation, and urinalysis) include all laboratory results, scheduled and unscheduled. 
These listings are not color-coded, but the severity should be included in parentheses after the result for abnormal results, e.g., 16.2 (Mild). The “extra” 
fields that are completed for abnormal results are not included in this listing; they are included in the listing of abnormal laboratory results that is 
included in the table shells document. Results outside of the reference range but not graded as Mild, Moderate, or Severe, should have ONR shown as 
the Severity Grade. Change from Baseline column will be blank for parameters that are not numeric. 
Sort order: Parameter, Dose Group, Subject ID, and Timepoint.] 
Dose Group 
Subject ID 
Timepoint 
Date of 
Assessment 
Sex 
Laboratory Parameter 
(Units) 
Result 
(Severity Grade) 
Change from 
Baseline 
Reference Range 
40 mg Fasted 
PHU.00123 
Day 4 
 
Female 
Sodium (mEq/L) 
132 (Mild) 
-7 
131-132 
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
 
 


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Listing 13: 
16.2.8.2: Clinical Laboratory Results – Hematology 
[Implementation Note: 
Sort order: Parameter, Dose Group, Subject ID, Timepoint, and Date of Assessment.] 
Dose Group 
Subject ID 
Timepoint 
Date of 
Assessment 
Sex 
Laboratory Parameter 
(Units) 
Result 
(Severity Grade) 
Change from 
Baseline 
Reference Range 
 
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
 
 


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Listing 14: 
16.2.8.3: Clinical Laboratory Results – Coagulation 
[Implementation Note:  
Sort order: Parameter, Dose Group, Subject ID, Timepoint, and Date of Assessment.] 
Dose Group 
Subject ID 
Timepoint 
Date of 
Assessment 
Sex 
Laboratory Parameter 
(Units) 
Result 
(Severity Grade) 
Change from 
Baseline 
Reference Range 
 
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
 
 


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Listing 15: 
16.2.8.3: Clinical Laboratory Results – Urinalysis 
[Implementation Note: Change from baseline will not be calculated for character results. The change from baseline cell should be “-“ for those rows.  
Sort order: Parameter, Dose Group, Subject ID, Timepoint, Date of Assessment.] 
Dose Group 
Subject ID 
Timepoint 
Date of 
Assessment 
Sex 
Laboratory Parameter 
(Units) 
Result 
(Severity Grade) 
Change from 
Baseline 
Reference Range 
 
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
 


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16.2.9 Individual Screening Measurements 
Listing 16: 
16.2.9.1: Screening Laboratory Results – Serology 
[Sort Order: Dose Group, Subject ID, Visit (visit order: Screening, Admission, Unscheduled).] 
Dose Group 
Subject ID 
Visit 
HIV Antibodies 
HCV Antibodies  
HBsAg 
40 mg Fasted 
PHU.00123 
Screening 
Negative 
Negative 
Negative 
40 mg Fasted 
PHU.00123 
Unscheduled (Day 4) 
Negative 
Negative 
Negative 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 


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Listing 17: 
16.2.9.1: Screening Laboratory Results – Urine Toxicology  
[Implementation Note: If there are results for urine toxicology or alcohol breathalyzer tests on an Unscheduled visit, then the Study Day will be included 
in parentheses for the Visit. 
Sort order: Dose Group, Subject ID, Visit (visit order: Screening, Admission, Unscheduled).] 
Dose Group 
Subject ID 
Visit 
Cannabinoids 
Amphetamines 
Barbituates 
Cocaine 
Opiates 
Benzodiazepines 
Phencyclidine 
Alcohol  
Cotinine 
40 mg 
Fasted 
PHU.00123 
Screening 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
40 mg 
Fasted 
PHU.00123 
Admission 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
40 mg 
Fasted 
PHU.00123 
Unschedule
d (Day 4) 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
 
 


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Listing 18: 
16.2.9.1: Screening Laboratory Results – Serum hCG and FSH Tests 
[Implementation Note: If there are results for serum hCG on an Unscheduled visit, then the Study Day will be included in parentheses for the Visit. If 
obtained, FSH testing results will be shown in this listing.] 
Sort order: Dose Group, Subject ID, Visit (visit order: Screening, Admission, Unscheduled).] 
Dose Group 
Subject ID 
Visit 
Serum HCG Result 
FSH Test Result 
40 mg Fasted 
PHU.00123 
Screening 
Negative 
ND 
  
  
  
  
 
  
  
  
  
 
Note: ND=Test not performed 
 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 19: 
16.2.9.1: Vital Signs 
[Implementation Note: This listing includes all vital sign assessments, scheduled and unscheduled. All height, weight, and BMI measurements will also 
be included in this listing. These listings are not color-coded, but the severity should be included in parentheses after the result for abnormal assessments, 
e.g., 100.7 (Mild).  
Sort order: Dose Group, Subject ID Parameter (order: Height, Weight, BMI, Systolic Blood Pressure, Diastolic Blood Pressure, Pulse, Respiratory Rate, 
Temperature), Timepoint, Date of Assessment, Time of Assessment.] 
Dose Group 
Subject ID 
Parameter (units) 
Timepoint 
Date of 
Assessment 
Time of 
Assessment  
Result (Severity) 
Change from 
Baseline 
Reason for 
Repeat 
40 mg Fasted 
PHU.00123 
Systolic Blood Pressure 
(mmHg) 
Day 1, 1 h Post 
Dose 
ddMMMyyy 
hh:mm 
142 (Mild) 
10 
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
 
 
 


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Listing 20: 
16.2.9.2: Abnormal Physical Exam Findings 
[Implementation Note: This listing includes all physical exam findings, scheduled and unscheduled. If a subject does not have any findings upon 
examination, they will not be included in this listing. If reported as an AE, display “Yes” with the AE description and number in parentheses, e.g., “Yes 
(AE Description; 007)”.  
Sort order: Dose Group, Subject ID, Timepoint, Date of Assessment, Time of Assessment, Body System, and Finding.] 
Dose Group 
Subject ID 
Timepoint 
Date of 
Assessment 
Time of 
Assessment  
Body System 
Abnormal 
Findings 
Reported as an AE? (AE 
Description; Number) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 


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16.2.9 Individual ECG Results 
Listing 21: 
16.2.9.1: Listing of ECG Interval Measurements 
[Implementation Note: This listing includes all ECG assessments, scheduled and unscheduled. These listings are not color-coded, but the severity should 
be included in parentheses after the result for abnormal assessments, e.g., 100.7 (Mild). For the mean of triplicate readings, no assessment time should be 
presented and the replicate number should specify “Mean”.  
Sort order: Dose Group, Subject ID, Parameter, Date of Assessment, Time of Assessment.] 
Dose 
Group 
Subject ID 
Sex 
Parameter 
Timepoint 
Assessment Date 
Assessment Time 
Result 
(Severity) 
Change from 
Baseline 
Replicate 
Number 
Reason for 
Repeat 
40 mg  
Fasted 
PHU.00123 
Male 
PR Interval 
Day 4 
ddMMMyyy  
hh:mm 
450 (Mild) 
25 
1 
 
  
  
  
  
 
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
 
 


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Listing 22: 
16.2.9.1: Listing of ECG Overall Interpretation and Comments 
[Implementation Note: This listing includes all ECG assessments, scheduled and unscheduled.  
Sort order: Dose Group, Subject ID, Date of Assessment, Time of Assessment.] 
Dose Group 
Subject ID 
Sex 
Timepoint 
Assessment Date 
Interpretation 
Comments 
Reason for Repeat 
40 mg Fasted 
PHU.00123 
Male 
Day 4 
ddMMMyyy 
Abnormal NCS 
Sinus Bradycardia 
 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
 


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Listing 23: 
16.2.9.1: Listing of ECG Findings 
[Implementation Note: This listing will contain observations of the EG domain, subset to contain observations where EGCAT=“FINDING” and 
EGTESTCD^=“INTP”. The Category column will be based on EG.EGTEST and the Finding column will be based on EG.EGORRES.  
Sort order: Dose Group, Subject ID, Date of Assessment, Time of Assessment, Category (EGTEST), and Finding (EGSTRESC).] 
 Dose Group 
Subject ID 
Timepoint 
Date of Assessment 
Category 
Finding 
40 mg Fasted 
PHU.00123 
Day 4 
ddMMMyyy 
Sinus Node Rhythms and Arrhythmias 
SINUS ARRHYTHMIA 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 


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16.2.11 Pregnancy Reports 
Listing 24: 
16.2.11.1: Pregnancy Reports – Maternal Information 
[Implementation Note: Only include the “Pregnancy Number” column if a subject has more than 1 pregnancy. Date of Conception will be calculated 
based on estimated delivery date. BMI will be calculated based on pre-pregnancy height and weight. Mother’s weight gain will be calculated based on 
pre-pregnancy weight and end of pregnancy weight. If a major congenital anomaly with previous pregnancy, display “Yes” and the text from the 
“specify” field, separated by a colon. If any substance use is reported, include a listing of substance use. If autopsy revealed an alternate etiology, display 
“Yes” and the text from the “specify” field, separated by a colon. If abnormality in product of conception, display “Yes” and the text from the “specify” 
field, separated by a colon. In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-identification. Sort order: Dose Group, Subject 
ID, Pregnancy Number.] 
Dose 
Group  
Subject 
ID  
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications Listing. 
 


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Listing 25: 
16.2.11.2: Pregnancy Reports – Gravida and Para 
Live Births 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PBa 
Very 
Early 
PBa 
Early 
PBa 
Late 
PBa 
Early 
TBb 
Full 
TBb 
Late 
TBb 
Post 
TBb 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly 
with 
Previous 
Pregnancy? 
Note: Gravida includes the current pregnancy, para events do not. 
a Preterm Birth 
b Term Birth 
     Extremely PB: <25 weeks 
     Very Early PB: 25 0/7-31 6/7 weeks 
     Early PB: 32 0/7-33 6/7 weeks 
     Late PB: 34 0/7-36 6/7 weeks 
     Early TB: 37 0/7-38 6/7 weeks 
     Full TB: 39 0/7-40 6/7 weeks 
     Late TB: 41 0/7-41 6/7 weeks 
     Post TB: ≥42 0/7 weeks 


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Listing 26: 
16.2.11.3: Pregnancy Reports – Live Birth Outcomes 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 1 
minute 
Apgar 
Score, 5 
minutes 
Cord pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month of 
Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital Anomalies are included in the Adverse Event listing. 
 


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Listing 27: 
16.2.11.4: Pregnancy Reports – Still Birth Outcomes 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome (for 
this Fetus) 
Fetal Distress 
During Labor 
and Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, Etiology 
for Still Birth 
Identified? 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 28: 
16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Subject 
ID 
Date of Initial 
Report 
Fetus Number 
Pregnancy Outcome 
(for this Fetus) 
Gestational Age at 
Termination 
Abnormality in Product of Conception? 
Reason for Therapeutic 
Abortion 
 
 
 
 
 
 
 
 


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Listing 29: 
16.2.11.6: Birth Control Listing 
[Implementation Note: If subject is not of childbearing potential, indicate the reason that the subject is not of childbearing potential in parentheses in the 
“Childbearing Potential” column.  
Sort order: Dose Group, Subject ID, and Birth Control Start Day.] 
Dose Group 
Subject ID 
Sex 
Childbearing Potential 
Birth Control Method 
Birth Control Start Day 
Birth Control End Day 
40 mg Fasted 
PHU.00123 
Female 
Yes 
Hormonal Injections 
-100 
Ongoing 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 


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16.2.10 Subject Level PK Concentrations 
Listing 30: 
16.2.10: Subject Level VT-1598 and VT-11134 Concentrations – Plasma 
[Implementation Note: Units of nominal time and actual timepoint vary by timepoint and will be provided for each time rather than in the column 
heading. Laboratory Reported Concentration will give verbatim value reported by lab (with minimal formatting, as needed) and will use a character 
value such as PC.PCORRES. Analysis Concentration will report the value actually used for analysis and will use a numeric variable such as 
ADNCA.AVAL. If one or more samples are excluded from NCA, two additional columns will be provided in the PK report listing: Excluded from NCA 
(Yes/No) and Reason for Exclusion from NCA.  
In the actual time column, mark out of window times with one asterisk (*), mark substantially out of window times with two asterisks (**), and mark 
imputed times with three asterisks (***) 
Sort order: Dose Group, Subject ID, Analyte (VT-1598 then VT-11134), and Actual Time.] 
Dose Group 
Analyte 
Subject ID 
Nominal Timea  
Actual Timea  
Laboratory Reported 
Concentration (ng/mL) 
Analysis Concentrations 
(ng/mL) 
Used in λz 
Calculations 
40 mg  Fasted 
VT-1598 
PHU.00123 
0 h 
0 h 
0 
0 
No 
  
 
  
  
  
  
  
  
a Times are relative to time of dosing. For actual time, out of window times are indicated by an asterisk (*), substantially out of window times are indicated by two asterisks (**) and imputed times are 
indicated by three asterisks (***).  
BQL=Below the Limit of Quantification 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
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Listing 31: 
16.2.10: Subject Level VT-1598 and VT-11134 Concentrations – Urine 
[Implementation Note: Units of nominal time and actual timepoint vary by timepoint and will be provided for each time rather than in the column 
heading. Laboratory Reported Concentration will give verbatim value reported by lab (with minimal formatting, as needed) and will use a character 
value such as PC.PCORRES. Analysis Drug Concentration will report the value actually used for analysis and will use a numeric variable such as 
ADNCA.AVAL. If one or more samples are excluded from NCA, two additional columns will be provided in the PK report listing: Excluded from NCA 
(Yes/No) and Reason for Exclusion from NCA.  
In the actual time column, mark out of window times with one asterisk (*) and mark imputed times with three asterisks (***). 
Sort order: Dose Group, Analyte (VT-1598 then VT-11134), Subject ID, and Actual Time.] 
Dose Group 
Analyte 
Subject ID 
Nominal Collection 
Intervala 
Actual Collection 
Intervala 
Laboratory Reported 
Concentration (ng/mL) 
Urine Volume (mL) 
Analysis 
Concentrations 
(ng/mL) 
Total Amount 
Excreted From 
Urine (mg) 
40 mg  Fasted 
VT-1598 
PHU.00123 
0-6 h 
0-6 h 
0 
100 
0 
No 
  
 
  
  
  
  
 
  
  
aTimes are relative to time of dose. For actual time, out of window times are indicated by an asterisk (*) and imputed times are indicated by three asterisks (***). 
BQL=Below Quantitative Limit 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Listing 32: 
Subject Specific VT-1598 Plasma PK Parameters 
[Implementation Note: Sort order: Dose Group, Subject ID.] 
Dose 
Group 
Subject 
ID 
Cmax 
(ng/mL) 
Cmax/Dose 
(ng/mL/mg) 
Tmax 
(h) 
AUC0-last 
(ng*h/mL) 
AUC0-last/Dose 
((ng*h/mL)/mg) 
AUC(0-inf) (ng*h/mL) 
AUC(0-inf)/Dose 
((ng*h/mL)/mg) 
λz 
(1/h) 
t1/2 
(h) 
CL/F 
(L/h) 
Vd/F 
(L) 
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
  
  
  
  
 
Listing 33: 
Subject Specific VT-11134 Plasma PK Parameters 
This listing will repeat Listing 32 for VT-11134 PK parameters in plasma.  
 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
-- 201 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Listing 34: 
Subject Specific VT-1598 Urine Inpatient Period PK Parameters 
[Sort Order: Dose Group (40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted), Subject ID.] 
Dose Group 
Subject ID 
Aelast (mg) 
Ae%Dose (%) 
CLR (mL/min) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 17-0087 
 Version 1.0 
05JAN2022 
-- 202 - 
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Listing 35: 
Subject Specific VT-1598 Urine Nominal Collection Time Interval PK Parameters 
[Sort Order: Dose Group (40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted), Subject ID.] 
Dose Group 
Subject ID 
Ae0-6 (mg) 
Ae6-12 (mg) 
Ae12-24 (mg) 
Ae24-36 (mg) 
Ae36-48 (mg) 
Ae48-60 (mg) 
Ae60-72 (mg) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Listing 36: 
Subject Specific VT-11134 Urine Inpatient Period PK Parameters  
[Sort Order: Dose Group (40 mg Fasted, 80 mg Fasted, 160 mg Fasted, 160 mg Fed, 320 mg Fasted, 640 mg Fasted), Subject ID.] 
Dose Group 
Subject ID 
Aelast (mg) 
CLR (mL/min) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Listing 37: 
Subject Specific VT-11134 Urine Nominal Collection Time Interval PK Parameters 
This table will repeat Listing 35 for VT-11134 in urine.