Clinical trial NCT03800173
Conditions: Marburg Virus Disease
Sponsor: BioCryst Pharmaceuticals
Start date: 2018-12-10; Completion date: 2019-04-30
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics of galidesivir following administration of single doses by IV infusion

Detailed description:
This single ascending dose study will evaluate the safety, tolerability, and PK of single doses of galidesivir vs. placebo administered as IV infusions in healthy subjects enrolled in up to four dose cohorts of 8 subjects each. A single dose of study drug will be administered per cohort: 6 subjects will receive galidesivir IV, and 2 subjects will receive matching placebo.

Arms: arm 1: Galidesivir IV infusion arm 2: Placebo IV infusion
Interventions: intervention 1: galidesivir intervention 2: placebo
Intervention descriptions: intervention 1: galidesivir IV infusion intervention 2: placebo IV infusion

Protocol documents:
Prot_000.pdf: 
Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
1  
BIOCRYST 
PHARMACEUTICALS, INC. 
GALIDESIVIR (BCX4430) 
BCX4430-106/DMID 18-0013 
IND NUMBER: 137,833 
DMID FUNDING MECHANISM: CONTRACT NO.: 
HHSN272201300017C  
A PHASE 1 DOUBLE-BLIND, 
PLACEBO-CONTROLLED, DOSE-RANGING STUDY 
TO EVALUATE THE SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF GALIDESIVIR (BCX4430) 
ADMINISTERED AS SINGLE DOSES VIA 
INTRAVENOUS INFUSION IN HEALTHY SUBJECTS 
 
Version 3.0: 11 Jan 2019 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Blvd., Suite 200 
Durham, NC 27703 
Phone: (919) 859-1302 
Fax: (919) 851-1416 
CONFIDENTIAL 
The information in this document contains proprietary and confidential information belonging to 
BioCryst Pharmaceuticals, Inc. As a result, no part of this document should be copied, referred to, 
released, published or otherwise disclosed in any manner or media without prior written approval 
from BioCryst Pharmaceuticals, Inc.  
 
 
 
 




Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
3  
STATEMENT OF COMPLIANCE 
The study 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), 21 CFR 812 (Investigational Device Exemptions) 
• 
International Conference on Harmonisation: 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 




Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
5  
KEY ROLES 
 
Table 1: 
Contact Information 
Role in Study 
Name 
Address and Telephone 
Number 
Principal Investigator 
Daniel Dickerson, MD, PhD 
PRA Health Sciences – Lenexa 
9755 Ridge Dr, Lenexa, KS 
66219 
(+1) 913-205-4397 
BioCryst Medical Monitor 
Diane Gesty-Palmer 
Senior Medical Director 
BioCryst Pharmaceuticals 
4505 Emperor Blvd, Suite 200 
Durham, NC 27703 
Mobile: (+1) 919-423-7444 
mmgalidesivir@biocryst.com 
safety@biocryst.com 
Clinical Pharmacologist 
Amanda Mathis, PhD 
Director, Clinical 
Pharmacology 
BioCryst Pharmaceuticals 
4505 Emperor Blvd, Suite 200 
Durham, NC 27703 
Office: (+1) 919-226-5811 
amathis@biocryst.com 
BioCryst Clinical Study Manager 
Lauren Sherwood 
Clinical Study Manager 
BioCryst Pharmaceuticals 
4505 Emperor Blvd, Suite 200 
Durham, NC 27703 
Office (+1) 919-859-7903 
lsherwood@biocryst.com 
Institutions 
 
 
      Clinical Unit 
PRA Health Sciences - 
Lenexa 
PRA Health Sciences – Lenexa 
9755 Ridge Dr 
Lenexa, KS 66219 
      Central Laboratory 
Quest Laboratories 
Quest Diagnostics 
10101 Renner Blvd 
Lenexa, KS 66219 
      Bioanalytical Laboratory 
Covance Laboratories 
Covance Laboratories 
3301 Kinsman Blvd 
Madison, WI 53704 


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
6  
1. 
SYNOPSIS 
Name of Sponsor/Company: 
BioCryst Pharmaceuticals, Inc. 
Name of Investigational Product: 
Galidesivir (BCX4430) 
Name of Active Ingredient: 
(2S, 3S, 4R, 5R)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine-3,4-
diol dihydrochloride 
Protocol Number: 
BCX4430-106/DMID 18-0013 
Phase: 1 
Country: US 
Title of Study:  
A Phase 1 double-blind, placebo-controlled, dose-ranging study to evaluate the safety, tolerability, 
and pharmacokinetics of galidesivir (BCX4430) administered as single doses via intravenous infusion 
in healthy subjects 
Study center: PRA Lenexa, Kansas  
Principal Investigator:  
Investigators: 
Studied period (years):  
Estimated date first subject enrolled: OCT 2018 
Estimated date last subject completed: JAN 2019 
Phase of development: 1 
 
Objectives:  
Primary: 
• 
To evaluate the safety and tolerability of single ascending doses (SAD) of galidesivir (BCX4430) 
administered by intravenous (IV) infusion in healthy subjects 
Secondary: 
• 
To characterize the plasma pharmacokinetic (PK) profile and urinary elimination of SAD of 
galidesivir administered by IV infusion in healthy subjects 
Endpoints: 
Primary: 
• 
Safety and tolerability parameters including adverse events (AEs) and serious adverse events 
(SAEs), laboratory abnormalities, vital signs, electrocardiograms (ECGs), echocardiograms 
(ECHOs), cardiac telemetry, and physical examination (PE)  
Secondary: 
• 
Plasma and urine PK parameters for galidesivir 
• 
Dose proportionality of galidesivir 
Methodology:  


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
7  
This SAD study will evaluate the safety, tolerability, and PK of single doses of galidesivir vs. placebo 
administered as IV infusions in healthy subjects enrolled in up to four dose cohorts of 8 subjects each. 
A single dose of study drug will be administered per cohort: 6 subjects will receive galidesivir IV, and 
2 subjects will receive matching placebo.   
The planned cohorts are as follows: 
• 
Cohort 1, Regimen A: 5 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• 
Cohort 2, Regimen B: 10 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• 
Cohort 3, Regimen C: 15 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• 
Cohort 4, Regimen D: 20 mg/kg galidesivir or placebo, IV infusion × 1 dose 
Study drug will be infused IV over 60 minutes at a maximum infusion rate of 8.33 mL/min.   
As a safety precaution, on the first day of dosing in all cohorts, only 2 subjects will be dosed (to be 
referred to as sentinel subjects). The randomization schedule will be constructed such that 1 of the 
sentinel subjects dosed on the first day will be randomized to receive galidesivir and 1 will be 
randomized to receive placebo. After review of the safety data from the 24-hour post-dose period for 
the sentinel subjects, which includes review of any AEs, any abnormalities in the bedside ECGs, 
safety laboratory assessments and vital signs as described in Section 7.6.1, the remainder of the cohort 
(5 subjects randomized to galidesivir; 1 randomized to placebo) will be dosed at least 2 days after the 
sentinel subjects. 
Following a 28-day screening period to determine eligibility, subjects in each cohort will be admitted 
to the Clinical Research Unit (CRU) on Day -1. Study eligibility will be confirmed upon admission to 
the CRU, and subjects will remain in the CRU overnight prior to dosing on Day 1. Following 
administration of study drug on Day 1, subjects will remain in the CRU for 96 hours to enable 
collection of PK samples and safety and tolerability data. Subjects will be discharged from the CRU 
on Day 5, 96 hours after the start of the infusion. Subjects will return to the CRU for a brief visit 
(approximately 1 to 2 hours) for PK sample collection on Day 6 (+ 1 day), Day 8 (+ 1 day), and Day 
14 (± 1 day). Subjects will return to the CRU for a final follow-up visit on Day 21 (+ 2 days). In the 
event that there are any unresolved safety findings that are ongoing at Day 21, the subject will be 
followed at additional study visits until the findings are resolved or stabilized. If it is determined that 
the median half-life is longer than anticipated following IV infusion, or if after obtaining PK data 
through 96 hours, the area under the concentration-time curve (AUC) extrapolated to infinity (AUCinf) 
estimate is > 25% of the AUC from time 0 to the last measurable concentration of drug (AUClast), 
serial PK sampling may be extended beyond 96 hours in subsequent cohorts, or additional samples 
may be added in the intervening period between discharge from the CRU and the final follow-up visit 
at Day 21 (+2 days).   
Safety and tolerability will be evaluated through assessments of AEs, laboratory analyses (clinical 
chemistry, hematology, coagulation, urinalysis, creatine kinase-MB [CK-MB], troponin), vital signs, 
ECGs, ECHOs, cardiac telemetry, and PE examination findings at the time points indicated in the 
schedule of assessments. PK parameters will be analyzed from the plasma and urine samples 
collected at the time points indicated in the schedule of assessments.  
Dose Escalation Decision Process: Enrollment of subjects in each sequential higher dose level cohort 
will occur only after completion of a clinical safety review of laboratory, AE, vital sign, ECG 
(12-lead and telemetry), and PE data for all subjects up through 96 hours post-dose and plasma PK 
data through 24 hours post-dose, by the Sponsor medical monitor, clinical pharmacologist, and 
principal investigator (PI) at a dose escalation review meeting. Safety data summaries will be 
prepared by the PI; PK analyses will be performed by the clinical pharmacologist; and the dose 
escalation safety review summary and decision will be documented by the PI and clinical 


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
8  
pharmacologist. Based upon safety review and evaluation of the data for each subject, adjustments in 
the dose escalation scheme for the next cohort may be made, including omission of higher dose 
cohorts in the event that the safety and PK parameters have been adequately characterized with lower 
dose cohorts. Where considered appropriate to meet the study objectives, adjustments in the protocol-
specified dose escalation for subsequent cohorts are permissible (i.e., an intermediate dose between 
the previous tolerable dose and the scheduled next higher dose). Dose escalation will be stopped if 
any one of the stopping criteria are met. The highest dose stated in the protocol will not be exceeded 
without a protocol amendment.   
Criteria for stopping dose escalation for review of the PK and safety data: 
• 
One or more subjects with a treatment-emergent QT interval corrected by Fridericia's 
formula (QTcF) > 480 ms (Grade 2 per the DMID scale) as determined from bedside 
ECGs (with repeat ECG). If this occurs, the SMC may consult with an independent 
cardiologist as needed.  If it is deemed acceptable to restart the study following review of 
the data and discussion with an independent cardiologist, if needed, dosing may resume. 
• 
One or more subjects experiences an increase in BP that requires acute treatment, or has a 
confirmed systolic BP > 160 mmHg, or a confirmed diastolic BP > 100 mmHg (Grade 3 
per DMID scale). Confirmed BP changes require at least 2 measurements at least 2 hours 
apart, each measured after at least 5 minutes of supine rest. 
• 
Anaphylactic reaction occurs in 1 subject. 
• 
One or more subjects experience a similar Grade 3 treatment-emergent laboratory 
abnormality or AE that is suspected to be drug-related as determined by the investigator. 
• 
One subject experiences an SAE. 
• 
A cohort’s median AUC from time 0 to 24 hours (AUC24) is ≥ 52,500 ng.h/mL, 
equivalent to the NOAEL exposure in cynomolgus monkeys.   
Sample Size Justification: 
No formal power or sample size calculations were used to determine cohort sizes. Cohort sizes were 
based upon experience in other SAD Phase 1 studies. A sample size of 6 subjects receiving active 
drug per cohort should provide adequate characterization of PK and safety assessments within this 
setting. 
Number of subjects (planned):  
32 subjects, with 8 subjects enrolled per cohort (6 receiving galidesivir and 2 receiving placebo) 
Criteria for inclusion:  
1. Able to provide written, informed consent. 
2. Males or non-pregnant, non-lactating females age 18–55 years. 
3. Body mass index of 19.0 to 32.0 kg/m2, inclusive 
4. Weight ≥ 50 kg (110 lb.) and ≤ 100 kg (220 lb.) 
5. Male and female subjects must agree to the contraception requirements and must meet the 
inclusion criteria regarding contraception as outlined in the protocol.  
6. Has normal vital signs at screening visit at rest, after 10 minutes in a supine position: 
‒ 
Oral temperature < 38°C; no recent hot or cold beverages  


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
9  
‒ 
Resting heart rate is between 60–100 beats per minute (bpm). If a subject is a young 
healthy volunteer without cardiac disease or symptomatology, heart rate 45–59 bpm 
will be allowed.  
‒ 
BP: systolic ≥ 90 mmHg and ≤ 140 mmHg, diastolic ≥ 40 mmHg and ≤ 90 mmHg 
‒ 
Respiratory rate < 20 respirations per minute 
7. Suitable veins for cannulation/multiple venipunctures as assessed by the investigator or 
designee at screening. 
8. In the opinion of the investigator, the subject is able and willing to adequately comply with 
all required study procedures and restrictions for the duration of the study. 
Criteria for exclusion:       
1. Any clinically significant medical conditions or medical history that, in the opinion of the 
investigator or Sponsor, would interfere with the subject’s ability to participate in the study or 
increase the risk of participation for that subject*.  
*Note:  Significant medical history would include, but not be limited to, kidney disease with creatinine clearance < 
90 mL/min/1.73m2, known active liver disease (including steatosis), ischemic heart disease, cardiac conduction 
disorder, chronic intestinal disease, hypertension (including treated), arrhythmia requiring treatment, diabetes 
requiring insulin, neuropathy, myopathy, and malignancy (not including squamous cell skin cancer, basal cell skin 
cancer, or cervical low-grade squamous intraepithelial lesions).    
2. Any clinically significant psychiatric condition or history of psychiatric condition that, in the 
opinion of the Investigator or Sponsor, would interfere with the subject’s ability to participate 
in the study or increase the risk of participation for that subject. 
3. Abnormal ECG at the screening visit*.  
*Note:  Abnormalities include but are not limited to, a QTcF > 450 ms in men or >460 ms in women, a PR > 220 
ms, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or 
higher in grouping, second or third degree heart block, or long QT syndrome.   
4. Clinically significant abnormalities found on the screening echocardiogram*.  
*Note: abnormalities include but are not limited to:  ejection fraction < 55% or structural 
abnormalities such as valvular and septal defects. Incident mitral valve prolapse with none-to-trace 
regurgitation is not an exclusion. 
5. Known family history of sudden death or long QT syndrome, or family or personal history of 
QT prolongation or poison/drug-induced arrhythmia that required medical intervention. 
6. History of or current implanted defibrillator or pacemaker. 
7. Any inclusion laboratory test performed at screening with an abnormal result that is DMID 
Grade 1 or greater. The inclusion tests are defined to be: alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), total bilirubin, creatinine, urine protein, hemoglobin, 
serum potassium, and white blood cell count.  
8. Any other screening laboratory test (other than the above stated inclusion tests) with an 
abnormal result that is DMID Grade 2 or higher.  
9. Current participation in any other investigational drug study or participation in an 
investigational drug study within 30 days of the Screening visit, or 5.5 half-lives of the 


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
10  
investigational drug.  Eligible subjects should not have more than 100 mL of blood 
withdrawn in an investigational study in the 30 days prior to participation in this study. 
10. Subject use of prescription, over-the-counter medications, or herbal supplements*, is 
prohibited during the study. 
*Note: an exception is the use of any contraceptive medication allowed under this protocol and 2 g/day 
of acetaminophen, for a period of 7 days prior to and during the study.  Over-the-counter medication 
including herbal products not otherwise excluded per Section 9.12 must be stopped 7 days prior to the 
study. 
11. History of alcohol or drug abuse in the year prior to the screening visit, or current evidence of 
drug dependence*.   
*Note: A positive result for any drug listed in Table 8 on the urine drug screen is exclusionary.   
12.  Self-reported alcohol intake > 3 drinks/day or a positive alcohol test at screening. 
13. A positive cotinine test 
14. Positive serology for human immunodeficiency virus or active infection with hepatitis B virus 
or hepatitis C virus. 
15. Pregnant, lactating, or has plans to become pregnant during the study or within 30 days of 
dosing. 
16. Donation or loss of > 400 mL of blood in the 3 months prior to screening. 
17. History of serious adverse reaction to or known serious hypersensitivity to any drug.  
18. Presence or history of severe allergic reaction with generalized urticaria, angioedema, or 
anaphylaxis requiring treatment, as judged by the Investigator.   
19. Employment by the study site, or an immediate family relationship to either study site 
employees or Sponsor employee. 
20. Male subjects with pregnant female partners. 
Investigational product, dosage and mode of administration:  
Galidesivir for IV infusion: galidesivir is dissolved in Sterile Water for Injection United States 
Pharmacopeia (USP) with a pH adjusted to 3.0. For the 60-minute IV infusion the drug product will 
be further diluted in Lactated Ringer’s (LR) solution (USP) to achieve a solution with pH of 
approximately 4.0 to 5.0.   
Duration of treatment:  
Single dose administration of galidesivir via a 60-minute infusion.   
For each cohort, a subject’s participation is anticipated to be approximately 7 weeks, including 
screening and the follow-up period. 
Reference therapy, dosage and mode of administration:  
Matched placebo for IV infusion to match active treatment. The placebo will be LR solution (USP).  
Criteria for evaluation: 
Safety: AEs, laboratory analyses (clinical chemistry, hematology, coagulation, urinalysis, CK-MB, 
troponin), vital signs, ECGs, ECHOs, cardiac telemetry, and physical examinations. 


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
11  
PK: Venous blood samples will be collected via an indwelling cannula or by venipuncture at regular 
intervals throughout the study. The plasma concentration data for galidesivir will be analyzed using 
non-compartmental techniques to obtain estimates of standard non-compartmental PK parameters, 
including:  maximum concentration (Cmax), last measurable concentration of drug (Clast), time to 
maximum concentration (Tmax), AUClast, AUCinf, clearance (CL), volume of distribution (Vz), 
percentage of AUC extrapolated between AUClast and AUCinf (AUCextrap), λz, and half-life (t1/2), and 
other parameters, where appropriate. 
Plasma Sampling: 
Samples will be collected pre-dose, 30 min (halfway through the infusion), 1 h (end of the infusion), 
1.25 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h,16 h, 24 h, 36 h, 48 h, 60 h, 72 h, and 96 h following 
the start of the infusion.  All sampling times are in relation to the start of the infusion.   
After discharge from the CRU, subjects will return to the CRU for a brief visit (approximately 1-2 
hours) for PK sample collection on Day 6 (+ 1 day), Day 8 (+ 1 day) and Day 14 (± 1 day). A PK 
sample will also be collected at the Day 21 (+ 2 days) follow-up visit or early termination visit (if 
applicable).   
Urine Sampling: 
Predose, 0–12 h, 12–24 h, 24–48 h, 48–72 h, 72–96 h.    
Statistical methods: 
Safety: 
AEs will be mapped to a Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
(PT) and system organ classification (SOC). Any event reported on the subject’s study record that 
occurs on or after the initiation of study drug is defined as treatment emergent. Additionally, it is 
assumed that an AE that is reported to have started on Day 1 of a given treatment period without an 
associated onset time may have occurred after the initiation of study drug. Hence, AEs occurring on 
Day 1 with no associated onset time will be assumed to be treatment emergent. The occurrence of 
treatment-emergent AEs will be summarized by cohort and treatment assignment using MedDRA PT, 
SOC, and severity.  Separate summaries of treatment-emergent SAEs and AEs considered to be 
related to study drug will be generated. All AEs will be listed for individual subjects showing both 
verbatim and preferred terms.  
Descriptive summaries of vital signs, ECG parameters (12-lead and telemetry), ECHOs, and clinical 
laboratory results will be presented separately for each cohort by study visit and treatment 
assignment. Laboratory abnormalities will be graded according to the modified DMID criteria (2014) 
in APPENDIX A. 
Physical examination results will be presented in listings.   
Concomitant medications will be coded using the World Health Organization Dictionary. These data 
will be summarized by cohort and treatment assignment. 
Pharmacokinetics: 
Concentrations of galidesivir will be determined by validated plasma and urine assays and will be 
summarized by treatment and displayed in figures. Plasma PK parameters for each subject will be 
estimated over the sampling interval using noncompartmental analysis (Phoenix WinNonlin 
Version 7.0 or higher, Certara) and summarized by treatment group using descriptive statistics. The 
amount and percentage of galidesivir excreted in the urine will be assessed at all doses.  


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
12  
Dose proportionality will be evaluated over all doses and will be based upon AUCinf, AUC from time 0 
to time “t” (AUCt), and Cmax using both the power model and the analysis of variance method. 


Protocol BCX4430-106/DMID 18-0013 
Galidesivir, Version 3.0 
13 
2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF
FIGURES
SIGNATURE PAGE .......................................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................4 
KEY ROLES ....................................................................................................................................5 
1.
SYNOPSIS ...................................................................................................................6 
2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
3.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................20 
4.
INTRODUCTION ......................................................................................................23 
4.1. 
Background .................................................................................................................23 
4.2. 
Nonclinical Findings ...................................................................................................23 
4.2.1. 
Nonclinical Pharmacology ..........................................................................................23 
4.2.2. 
Nonclinical Pharmacokinetics ....................................................................................24 
4.2.3. 
Nonclinical Toxicology ..............................................................................................24 
4.3. 
Clinical Findings .........................................................................................................25 
4.3.1. 
Study BCX4430-101 ..................................................................................................25 
4.3.1.1. 
BCX4430-101: Study Design .....................................................................................25 
4.3.1.2. 
Study BCX4430-101: Pharmacokinetic Results .........................................................26 
4.3.1.3. 
Study BCX4430-101: Safety and Tolerability ...........................................................27 
4.4. 
Rationale for Study .....................................................................................................28 
4.4.1. 
Study and Population ..................................................................................................28 
4.4.2. 
Rationale for Route of Administration .......................................................................29 
4.4.3. 
Rationale for Study Doses ..........................................................................................29 
4.5. 
Benefit-Risk Analysis .................................................................................................29 
4.5.1. 
Risks/Safety Signals Observed in the First-in-Human Intramuscular 
Injection Study with Galidesivir .................................................................................31 
4.5.2. 
Risks of Potential Adverse Events with Study-Mandated Procedures .......................32 
4.5.3. 
Risks Associated with Infusions .................................................................................32 
4.5.4. 
Known Potential Benefits ...........................................................................................32 
5.
STUDY OBJECTIVES AND PURPOSE ..................................................................33 
5.1. 
Primary Objective .......................................................................................................33 
5.2. 
Secondary Objectives .................................................................................................33 
6.
ENDPOINTS ..............................................................................................................33 


Protocol BCX4430-106/DMID 18-0013 
 
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14  
6.1. 
Primary Endpoints ......................................................................................................33 
6.2. 
Secondary Endpoints ..................................................................................................33 
7. 
INVESTIGATIONAL PLAN .....................................................................................33 
7.1. 
Overall Study Design ..................................................................................................33 
7.2. 
Number of Subjects ....................................................................................................39 
7.3. 
Treatment Assignment ................................................................................................39 
7.4. 
Randomization Procedures .........................................................................................39 
7.5. 
Masking Procedures ....................................................................................................39 
7.6. 
Dose Escalation and Continuation Criteria .................................................................40 
7.6.1. 
Criteria for Continuing to Dose Within a Cohort after Sentinel Subjects 
Have Been Dosed .......................................................................................................40 
7.6.2. 
Dose Escalation Criteria .............................................................................................41 
7.6.3. 
Study Drug and Study Halting Rules..........................................................................41 
7.6.3.1. 
Infusion Halting Rules ................................................................................................41 
7.6.3.2. 
Study Halting Rules ....................................................................................................42 
7.7. 
Criteria for Study Termination ...................................................................................42 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................43 
8.1. 
Subject Inclusion Criteria ...........................................................................................43 
8.2. 
Subject Exclusion Criteria ..........................................................................................44 
8.3. 
Additional Study Restrictions .....................................................................................46 
8.4. 
Subject Withdrawal Criteria .......................................................................................47 
8.4.1. 
Withdrawal from Study Drug and Study ....................................................................47 
8.5. 
Replacement of Subjects .............................................................................................47 
9. 
TREATMENT OF SUBJECTS ..................................................................................48 
9.1. 
Treatments Administered ............................................................................................48 
9.2. 
Description of Investigational Medicinal Product ......................................................48 
9.3. 
Description of Placebo ................................................................................................49 
9.4. 
Study Drug Packaging and Labeling ..........................................................................49 
9.5. 
Study Drug Storage .....................................................................................................49 
9.6. 
Study Drug Preparation ..............................................................................................50 
9.7. 
Administration ............................................................................................................50 
9.8. 
Treatment Compliance ................................................................................................50 
9.9. 
Study Drug Accountability .........................................................................................51 


Protocol BCX4430-106/DMID 18-0013 
 
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15  
9.10. 
Study Drug Handling and Disposal ............................................................................51 
9.11. 
Concomitant Medications ...........................................................................................51 
9.12. 
Prohibited Medications ...............................................................................................51 
9.13. 
Food and Drink ...........................................................................................................52 
10. 
STUDY CONDUCT ...................................................................................................52 
10.1. 
Schedule of Assessments ............................................................................................52 
10.1.1. 
Screening ....................................................................................................................52 
10.1.2. 
Study Procedures ........................................................................................................53 
10.1.3. 
Follow-up/Early Termination Visit ............................................................................55 
11. 
ASSESSMENTS.........................................................................................................55 
11.1. 
Investigator-Completed Assessments .........................................................................55 
11.2. 
Pharmacokinetic Assessments ....................................................................................56 
11.2.1. 
Blood Sample Collection ............................................................................................56 
11.2.2. 
Urine Sample Collection .............................................................................................56 
11.2.3. 
Sample Analysis .........................................................................................................56 
11.3. 
Assessment of Safety ..................................................................................................57 
11.3.1. 
Safety Parameters .......................................................................................................57 
11.3.1.1. 
Vital Signs ..................................................................................................................57 
11.3.1.2. 
Weight/Height/Body Mass Index ...............................................................................57 
11.3.1.3. 
Physical Examination .................................................................................................57 
11.3.1.4. 
12-Lead Electrocardiogram ........................................................................................57 
11.3.1.5. 
Cardiac Telemetry ......................................................................................................58 
11.3.1.6. 
Echocardiogram ..........................................................................................................58 
11.3.1.7. 
Clinical Laboratory Screening and Safety Assessments ............................................59 
11.4. 
Adverse Events and Serious Adverse Events .............................................................62 
11.4.1. 
Definition of Adverse Events .....................................................................................62 
11.4.1.1. 
Adverse Event .............................................................................................................62 
11.4.1.2. 
Serious Adverse Event ................................................................................................63 
11.4.1.3. 
Adverse Events of Special Interest .............................................................................64 
11.4.2. 
Relationship to Study Drug ........................................................................................65 
11.4.3. 
Recording Adverse Events .........................................................................................65 
11.4.4. 
Reporting Adverse Events ..........................................................................................65 
11.4.5. 
Regulatory Reporting ..................................................................................................66 


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11.4.6. 
Periodic Reporting ......................................................................................................67 
11.4.7. 
Reporting of Pregnancy ..............................................................................................67 
11.4.8. 
Urgent Safety Measures ..............................................................................................68 
11.4.9. 
Reporting of Urgent Safety Issues ..............................................................................69 
11.4.10. 
Serious Breaches .........................................................................................................69 
11.5. 
Safety Oversight .........................................................................................................69 
11.5.1. 
Independent Safety Monitor .......................................................................................69 
11.5.2. 
Dose Escalation Committee ........................................................................................69 
11.5.3. 
Safety Monitoring Committee ....................................................................................71 
12. 
STATISTICS ..............................................................................................................71 
12.1. 
Study Hypothesis ........................................................................................................71 
12.2. 
Sample Size Considerations .......................................................................................71 
12.3. 
Final Analysis Plan .....................................................................................................72 
12.3.1. 
Statistical Methods ......................................................................................................72 
12.3.1.1. 
Analysis Populations ..................................................................................................72 
12.3.1.2. 
Subject Demographic and Disposition Data ...............................................................72 
12.3.1.3. 
Analysis of Safety Variables ......................................................................................72 
12.3.1.4. 
Pharmacokinetic Analysis ..........................................................................................73 
12.3.1.5. 
Dose Proportionality of Galidesivir ............................................................................74 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................74 
13.1. 
Study Monitoring ........................................................................................................75 
13.2. 
Audits and Inspections ................................................................................................75 
13.3. 
Institutional Review Board .........................................................................................76 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................76 
15. 
ETHICS ......................................................................................................................76 
15.1. 
Ethics Review .............................................................................................................76 
15.2. 
Ethical Conduct of the Study ......................................................................................77 
15.3. 
Written Informed Consent ..........................................................................................77 
15.3.1. 
Informed Consent/Assent Process (in Case of a Minor) ............................................78 
15.4. 
Exclusion of Women, Minorities, and Children (Special Populations) ......................78 
15.5. 
Subject Confidentiality ...............................................................................................78 
15.6. 
Study Discontinuation ................................................................................................78 
15.7. 
Future Use of Stored Specimens .................................................................................78 


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15.8. 
Costs, Subject Compensation, and Research Related Injuries ...................................79 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................79 
16.1. 
Data Management Responsibilities ............................................................................79 
16.2. 
Data Capture Methods ................................................................................................79 
16.3. 
Types of Data ..............................................................................................................79 
16.4. 
Timing/Reports ...........................................................................................................80 
16.5. 
Inspection of Records .................................................................................................80 
16.6. 
Retention of Records ..................................................................................................80 
16.7. 
Protocol Deviations ....................................................................................................80 
17. 
PUBLICATION POLICY ..........................................................................................81 
18. 
LIST OF REFERENCES ............................................................................................82 
APPENDICES ...............................................................................................................................83 
APPENDIX A:  TOXICITY TABLE – MODIFIED DMID ADULT TOXICITY 
TABLE, 2014 .............................................................................................................84 
 
 


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LIST OF TABLES 
Table 1: 
Contact Information ......................................................................................................5 
Table 2: 
Abbreviations and Specialist Terms ...........................................................................20 
Table 3:  
Study BCX4430-101 Part 1: Summary of Select Plasma Pharmacokinetic 
Parameters Following Single Ascending Intramuscular Galidesivir Doses ...............26 
Table 4:  
Study BCX4430-101 Part 3: Summary of Select Plasma Pharmacokinetic 
Parameters Following 7-Day, Multiple Ascending Intramuscular Galidesivir 
Regimens (Days 1 and 7) ............................................................................................27 
Table 5: 
Schedule of Assessments ............................................................................................36 
Table 6:    Screening and Inclusion Laboratory Tests ...................................................................46 
Table 7: 
Dosing per Cohort .......................................................................................................48 
Table 8: 
Clinical Safety Laboratory Evaluations ......................................................................61 
Table 9: 
Pharmacokinetic Parameters .......................................................................................73 
 


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LIST OF FIGURES 
Figure 1: 
BCX4430-106 Study Design ......................................................................................35 
 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANOVA 
Analysis of variance 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC24 
area under the concentration-time curve from time 0 to 
24 hours  
AUCinf  
area under the concentration-time curve extrapolated to 
infinity  
AUCt  
area under the concentration-time curve from time 0 to 
time “t” 
AUCtau 
area under the concentration-time curve from time 0 to the 
end of the dosing interval 
BCX4430 
galidesivir 
BCX6870 
triphosphate active drug anabolite of galidesivir 
BMI 
body mass index 
BP 
blood pressure 
BQL 
below the quantitation limit 
CI 
confidence interval 
CK 
creatine kinase 
CK-MB 
creatine kinase-MB fraction 
Cmax 
maximum concentration 
CRF 
case report form  
CRU 
clinical research unit 
CSR 
clinical study report 
CV 
coefficient of variation  
DEC 
Dose Escalation Committee 
DMID 
Division of Microbiology and Infectious Diseases 


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Abbreviation or Specialist Term 
Explanation 
DSUR 
development safety update report 
EBOV 
Ebola virus 
ECG 
electrocardiogram  
ECHO 
Echocardiogram 
ECRF 
electronic case report form 
EF 
ejection fraction 
EVD 
Ebola virus disease 
FDA 
US Food and Drug Administration 
FSH 
follicle stimulating hormone  
GCP 
Good Clinical Practice 
GD 
gestational day 
GLP 
Good Laboratory Practice 
GLS 
geometric least squares 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus  
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IM 
intramuscular  
IMP 
investigational medicinal product 
IMPD 
investigational medicinal product dossier  
IND 
Investigational New Drug 
IP 
intraperitoneal  
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IV 
intravenous  
LR 
Lactated Ringer’s  
MAD 
multiple ascending dose  
MARV 
Marburg virus 
MedDRA 
Medical Dictionary for Regulatory Activities  
MTD 
maximum-tolerated dose 


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Abbreviation or Specialist Term 
Explanation 
MVD 
Marburg virus disease 
MVP 
mitral valve prolapse  
NGAL 
neutrophil gelatinase-associated lipocalin 
NHP 
non-human primate 
NIAID 
National Institute of Allergy and Infectious Diseases  
NIH 
National Institutes of Health 
NOAEL 
no observed adverse effect level 
NZW 
New Zealand White 
pc  
post-coitum  
PE 
physical examination  
PI 
principal investigator 
PK 
pharmacokinetic  
QD 
once daily 
QTcF 
QT interval corrected using Fridericia’s method 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information  
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard  
SMC 
Safety Monitoring Committee 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
Tmax 
time to Cmax 
UACR 
urine albumin to creatinine ratio 
USP 
United States Pharmacopeia 
 


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4. 
INTRODUCTION 
4.1. 
Background 
Marburg virus (MARV) belongs to the Filoviradae family of viruses.  Diseases caused by 
filoviruses are among the most lethal of primate pathogens (Changula, Kajihara et al. 2014). 
MARV is the causative agent of Marburg Virus disease (MVD), which was first discovered in 
1967 with a simultaneous outbreak in Marburg and Frankfurt, Germany and Belgrade, Serbia 
that was tied to use of nonhuman primates that were imported from Uganda. The natural host for 
the virus is thought to be fruit bats, with transmission to humans occurring from fruit bats, and 
then subsequent human-to-human transmission. Since that initial outbreak, outbreaks of MVD 
infections in humans have been sporadic and unpredictable, similar to outbreaks of other 
filovirus diseases. Mortality from MVD is high; case-fatality rates range from 23% to 88% 
(Kuhn, Dodd et al. 2011, CDC 2014, WHO 2017).   
No specific treatments are currently available for filovirus diseases.  In recent filovirus 
outbreaks, such as the Sudan Ebola virus disease (EVD) outbreak in 2014, both vaccines and 
direct antivirals have been investigated in clinical studies (Cross, Mire et al. 2018). After the 
outbreak, vaccines have been a focus for prevention of EVD, with several vaccines in 
development. Both medical countermeasures and vaccines that are effective against multiple 
filoviruses, are of interest for MVD.   
Galidesivir (also referred to as BCX4430 in study titles, study reports and supporting documents) 
is an adenosine analog that inhibits viral ribonucleic acid (RNA)-dependent RNA polymerase 
activity, and is being developed by BioCryst Pharmaceuticals Inc. (BioCryst, the Sponsor of this 
study) as a direct-acting antiviral drug (Julander, Bantia et al. 2012, Warren, Wells et al. 2014). 
The drug is currently being developed as an intravenous (IV) formulation as a post-exposure 
prophylaxis and for the treatment of confirmed or suspected MVD. 
4.2. 
Nonclinical Findings 
The results of nonclinical pharmacology, pharmacokinetics (PK), and toxicology studies of 
galidesivir are described briefly below; details can be found in the Investigator’s Brochure (IB). 
Nonclinical in vivo safety pharmacology and PK studies and in vitro safety pharmacology 
studies detailed in the IB support clinical studies with galidesivir as a parenterally administered 
antiviral drug. 
4.2.1. 
Nonclinical Pharmacology 
Galidesivir is a novel adenosine nucleoside analog, which inhibits viral RNA polymerase activity 
indirectly through non-obligate RNA chain termination. This mechanism involves anabolism of 
galidesivir to BCX4430 triphosphate (BCX6870). Galidesivir has broad-spectrum antiviral 
activity against bunyaviruses, arenaviruses, paramyxoviruses, picornaviruses, coronaviruses, and 
flaviviruses (Warren, Wells et al. 2014). In MARV-infected HeLa cells, galidesivir reduced 
production of intracellular MARV RNA, and reduced production of infectious virus (inhibitory 
concentration 90% value of 5.4 µM). Galidesivir decreased expression of MARV glycoprotein 
on the cell surface in virus-infected cells (effective concentration 50% values of 4.4, 6.7, and 
5.0 µM for MARV Musoke, Ci67, and Angola variants, respectively) (Warren, Wells et al. 
2014). 


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Galidesivir has been administered parenterally (intramuscular [IM], IV, or intraperitoneal [IP]) in 
multiple experiments conducted in nonclinical filovirus disease models. Reproducible evidence 
of efficacy was observed in the established mouse model that utilizes an Ebola Zaire Mayinga 
variant, adapted for pathogenicity in mice by serial passage (Bray, Davis et al. 1999, Warfield, 
Bradfute et al. 2009), with clear dose-related effects and statistically significant protection when 
dosing is delayed up to 96 hours post-infection. Similarly, galidesivir administration in 
nonclinical species infected with either mouse-adapted MARV (in mice), guinea pig-adapted 
MARV (in guinea pig), or wild-type MARV (in non-human primates [NHPs]) has shown 
reproducible evidence of efficacy. Statistically significant protection from mortality in 
experimental MVD models was observed when dosing was begun up to 48 hours post-infection 
in the NHP (Warren, Wells et al. 2014) and guinea pigs, and up to 96 hours post-infection in 
mice. Experiments in hamsters infected with the Jimenez variant of rodent-adapted yellow fever 
virus provide additional nonclinical evidence of efficacy of IP administered galidesivir in 
hemorrhagic fevers (Julander, Bantia et al. 2014).  
4.2.2. 
Nonclinical Pharmacokinetics 
The PK of galidesivir administered by IV bolus, IM injection, or oral gavage have been 
evaluated in several studies in mice, rats, guinea pigs, and non-human primates (NHP). A 
summary of the PK of galidesivir across species following IV bolus, IM injection, and oral 
administration can be found in the IB. 
In summary, when galidesivir is administered by IV bolus and IM injection routes, PK profiles 
are very similar and exposures (maximum concentration [Cmax] and area under the concentration-
time curve [AUC]) are indistinguishable. After IV infusion over 30 min, Cmax is lower compared 
to after IV bolus or IM injection. The PK profile in plasma in all species examined is 
characterized by a rapid distribution phase followed by a slow terminal clearance phase; the 
volume of distribution is high, indicating extensive tissue uptake. Exposure is approximately 
linearly proportional to dose. 14C-Galidesivir is rapidly distributed, with a tissue distribution 
profile in the rat that is not different for IV bolus and IM injection. The highest concentrations of 
administered radioactivity were seen in the liver. Mean dose-adjusted exposure to BCX6870 in 
liver was approximately 30- to 200-fold higher than that of parent drug in plasma. Metabolism of 
galidesivir is insignificant with no metabolites over 2% of dose. Galidesivir is excreted in the 
urine in the rat and monkey. 
4.2.3. 
Nonclinical Toxicology 
The nonclinical safety and toxicological evaluation of galidesivir has been conducted in vitro and 
in vivo in both a rodent species (rat) and NHP species (Cynolomolgus macaque) to support 
administration of IV infusions (and IM injections) to humans. Full details of these studies can be 
found in the IB.  
In vitro studies with galidesivir showed that galidesivir has a low concern for genotoxicity, is not 
toxic to mitochondrial function, did not inhibit human DNA polymerases, and has limited 
toxicity, compared with other antiviral compounds, on the proliferation of myeloid, erythroid and 
megakaryocyte progenitors, suggesting a low potential for bone marrow toxicity. 
Secondary and safety pharmacology studies suggest that galidesivir has a low potential to lead to 
unwanted cellular toxicities or effects in key mammalian functions, such as respiratory, central 


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nervous system (CNS), or electrocardiology. Increases in blood pressure (BP) and heart rate 
were observed at IM doses greater than 10 mg/kg in nonclinical studies in conscious monkeys. In 
vitro, galidesivir is compatible with human blood and does not cause hemolysis at 15 mg/mL, the 
highest concentration tested. Animal safety studies performed to support the IV infusion route of 
administration have used galidesivir formulated in Lactated Ringer’s (LR). 
Toxicity studies of galidesivir in the cynomolgus monkey and rat used the IV infusion 
(30  minutes) and IM administration routes. The systemic toxicologic profile for each route is 
similar. The primary target organs of toxicity in the rat were the kidney and liver, with toxicities 
also observed in the spleen, testes, thymus, heart, hematopoietic system, and IM injection sites. 
Target organs of toxicity in the monkey were kidney, liver, lymphoid system, and IM injection 
sites. Toxicities in both species were dose related. Microscopic changes in liver and kidney were 
correlated to monitorable changes in relevant clinical chemistry analytes, and reversible.   
4.3. 
Clinical Findings 
One study is complete in human subjects with data available (BCX4430-101). A brief 
description of the study, as well as a general summary of the safety and PK is described below; 
details can be found in the BCX4430-101 Clinical Study Report (CSR) and the IB. 
4.3.1. 
Study BCX4430-101 
4.3.1.1. 
BCX4430-101: Study Design  
Study BCX4430-101 was a 3-part, Phase 1, dose-ranging study of galidesivir administered by 
IM injection. In all parts of the study, safety and tolerability were evaluated through assessments 
of treatment-emergent adverse events (TEAEs), laboratory analyses (clinical chemistry, 
hematology, and urinalysis), vital signs, electrocardiograms (ECG; 12 lead and telemetry), 
echocardiograms (ECHOs), injection site assessments, and physical examinations (Pes). Subjects 
used a visual analog scale (VAS; 0–100 mm) to measure injection site pain following IM 
injection(s). In addition, study personnel performed clinical assessments at injection sites for 
erythema, pain, swelling, and tenderness.   
For the evaluation of galidesivir plasma PK parameters, blood samples were collected at multiple 
time points during the study. Dose proportionality was evaluated (power model and analysis of 
variance [ANOVA]) following single (Part 1) and multiple (Part 3) ascending galidesivir doses. 
The effect of lidocaine on the PK of galidesivir was evaluated (geometric least squares [GLS] 
mean ratios and 90% confidence intervals [CI]) in Part 2. Additionally, dose accumulation was 
evaluated (ANOVA) in Part 3.    
In Part 1, 6 ascending dose levels (0.3, 0.75, 1.8, 4.0, 7.0, and 10.0 mg/kg) were administered to 
separate cohorts of subjects in a double-blind, placebo-controlled fashion. Eight subjects 
received a single dose of study drug per cohort (6 subjects received galidesivir; 2 subjects 
received matching placebo). Subject dosing was staggered as a safety precaution.    
In parallel with Part 1 Cohort 6, 14 subjects in Part 2 completed a 2-period crossover evaluation 
of the effect of lidocaine on IM injections of galidesivir. Subjects received 4.0 mg/kg galidesivir 
with and without 20 mg lidocaine administered IM.  A summary of this part of the study, which 
is not relevant to IV infusion administration, can be found in the IB. 


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In Part 3, three ascending dose levels (2.5, 5.0, and 10.0 mg/kg) were administered to separate 
cohorts of subjects in a double-blind, placebo-controlled, sequential manner. Ten subjects 
received a 7-day course of study drug per dose cohort (8 subjects received galidesivir and 
2 subjects received placebo). Lidocaine was administered with all IM injections in Part 3.   
4.3.1.2. 
Study BCX4430-101: Pharmacokinetic Results 
The plasma PK concentration-time profile of galidesivir at all doses was characterized by rapid 
absorption, an initial rapid distribution and clearance phase, and a slow terminal clearance phase. 
Time to maximum concentration (Tmax) after IM administration of galidesivir was typically 
15 minutes (the first PK sample was drawn at 5 minutes). PK results from Part 1 of the study are 
presented in Table 3. Following single doses, galidesivir Cmax, AUC from time 0 to time “t” 
(AUCt), and AUC extrapolated to infinity (AUCinf) values increased in a slightly more than 
dose-proportional manner over the entire range of 0.3–10.0 mg/kg. The inter-subject variability 
in exposure (Cmax and AUC) was low, as reflected in the geometric mean coefficients of 
variation (CVs) on these parameters.   
 
The geometric mean (CV%) cumulative fraction of the dose appearing unchanged in the urine 
over 48 hours after single doses ranged from 23.7% (42.2%) to 34.3% (16.5%). 
Table 3:  
Study BCX4430-101 Part 1: Summary of Select Plasma Pharmacokinetic 
Parameters Following Single Ascending Intramuscular Galidesivir Doses 
 
PK 
Parameter 
Galidesivir 
0.3 mg/kg 
(N = 6)a 
0.75 mg/kg 
(N = 6) 
1.8 mg/kg 
(N = 6) 
4.0 mg/kg 
(N = 6) 
7.0 mg/kg 
(N = 6) 
10 mg/kg 
(N = 6) 
Cmax (ng/mL)a 
167 (30.5) 
n = 6 
562 (37.0) 
n = 6 
1000 (28.6) 
n = 6 
2760 (31.2) 
n = 6 
5760 (25.7) 
n = 6 
7980 (30.6) 
n = 6 
Tmax (h)b 
0.75 
(0.25, 1.05) 
n = 6 
0.25 
(0.25, 0.50) 
n = 6 
0.25 
(0.08, 0.25) 
n = 6 
0.25 
(0.25, 0.50) 
n = 6 
0.25 
(0.25, 0.25) 
n = 6 
0.375 
(0.25, 0.50) 
n = 6 
AUCt 
(ng.h/mL)a 
518 (18.6) 
n = 6 
1340 (7.0) 
n = 6 
3890 (8.0) 
n = 6 
10100 (12.1) 
n = 6 
18900 (12.0) 
n = 6 
27100 (17.7) 
n = 6 
AUCinf 
(ng.h/mL)a 
527 (9.9) 
n = 5c,d 
1650 (11.3) 
n = 4c,e 
4770 (6.4) 
n = 3f 
11900 (8.7) 
n = 3f 
24000 (13.7) 
n = 6 
32900 (21.0) 
n = 4e 
t1/2 (h)a 
4.44 (74.8) 
n = 5c 
48.1 (44.8) 
n = 5c 
81.4 (25.9) 
n = 6 
85.4 (28.2) 
n = 6 
77.9 (12.1) 
n = 6 
73.2 (27.5) 
n = 6 
Abbreviation: AUCinf = area under the concentration-time curve extrapolated to infinity; AUCt = area under the 
concentration-time curve from time 0 to time “t”; Cmax = maximum concentration; CV = coefficient of variation; 
max = maximum; min = minimum; PK = pharmacokinetic; t½ = half-life; Tmax = time to Cmax.  
a Data reported as geometric mean (CV% of geometric mean)  
b  Tmax reported as median (min, max) 
c  Data from 1 subject were excluded from summary statistics because R2 was < 7 
d  Data from 1 subject were excluded from summary statistics because the extrapolated portion of AUC was ≥ 25% 
e  Data from 2 subjects were excluded from summary statistics because the extrapolated portion of AUC was ≥ 25% 
f  Data from 3 subjects were excluded from summary statistics because the extrapolated portion of AUC was ≥ 25% 
Note: Study medication was administered IM. 
 


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PK parameters for Part 3 are presented in Table 4. On Days 1 and 7, over the multiple dose range 
of 2.5 to 10.0 mg/kg, AUC from time 0 to the end of the dosing interval (AUCtau) demonstrated 
dose proportionality; the increase in Cmax with dose was modestly greater than dose proportional 
with the power model and consistent with dose proportionality with the ANOVA model.  
Overall, there was an approximately 1.5-fold increase in exposure (AUC) with repeat dosing 
over 7 days. Assessment of trough concentrations of galidesivir suggested that steady state had 
not been achieved by Day 7.   
Table 4:  
Study BCX4430-101 Part 3: Summary of Select Plasma Pharmacokinetic 
Parameters Following 7-Day, Multiple Ascending Intramuscular Galidesivir 
Regimens (Days 1 and 7) 
PK Parameter 
2.5 mg/kg Galidesivir 
N = 7 
5.0 mg/kg Galidesivir 
N = 8 
10.0 mg/kg Galidesivir 
N = 8 
Day 1 
Day 7 
Day 1 
Day 7 
Day 1 
Day 7 
Cmax (ng/mL)a 
1820 (18.7) 
n = 7 
2390 (39.0) 
n = 7 
6840 (12.6) 
n = 8 
6900 (17.4) 
n = 8 
11400 (25.3) 
n = 8 
17500 (83.3) 
n = 7 
Tmax (h)b 
0.25 
(0.08, 0.50) 
n = 7 
0.25 
(0.10, 0.52) 
n = 7 
0.25 
(0.25, 0.50) 
n = 8 
0.25 
(0.08, 0.25) 
n = 8 
0.25 
(0.25, 0.25) 
n = 8 
0.25 
(0.08, 0.50) 
n = 7 
Ctau (ng/ mL)a 
33.6 (23.9) 
n = 7 
138 (19.1) 
n = 7 
68.4 (15.9) 
n = 8 
280 (17.8) 
n = 8 
134 (15.7) 
n = 8 
494 (16.6) 
n = 7 
AUCt (ng.h/mL)a 
4830 (16.9) 
n = 7 
15100 (16.1) 
n = 7 
12100 (11.6) 
n = 8 
32500 (11.5) 
n = 8 
21600 (10.1) 
n = 8 
62100 (13.9) 
n = 7 
AUCtau (ng.h/mL)a 
4830 (17.0) 
n = 7 
7620 (17.0) 
n = 7 
12100 (11.6) 
n = 8 
17600 (10.3) 
n = 8 
21700 (10.1) 
n = 8 
34500 (13.6) 
n = 7 
t1/2 (h)a 
NR 
104 (15.9) 
n = 7 
NR 
85.7 (17.3) 
n = 8 
NR 
113 (26.4) 
n = 7 
Abbreviations: AUCt = area under the concentration-time curve from time 0 to time “t”; AUCtau = area under the 
concentration-time curve from time 0 to the end of the dosing interval; Cmax = maximum concentration; Ctau = trough 
concentration; CV = coefficient of variation; max = maximum; min = minimum; IM = intramuscular; NR = not 
reported; PK = pharmacokinetic; QD once daily; t½ = half-life; Tmax = time to Cmax.  
a  Data reported as geometric mean (CV% of geometric mean)  
b  Tmax reported as median (min, max) 
Note: Galidesivir was administered QD IM with 20 mg of lidocaine over 7 days.  NR = not calculated due to 
24 hours not being a reliable time frame from which to estimate half-life and any related parameters. Lambda-based 
calculations truncated at the dosing interval were not summarized for Day 1. 
4.3.1.3. 
Study BCX4430-101: Safety and Tolerability  
Galidesivir was generally safe and well tolerated following single (0.3 to 10.0 mg/kg) and repeat 
(2.5 to 10.0 mg/kg) IM dosing in healthy subjects. No safety signals were detected. No subject 
experienced a serious adverse event (SAE) or a Grade 3 TEAE. No TEAE led to study 
discontinuation in Parts 1 or 2 of the study. Although study drug dosing was discontinued in 
1 subject (10.0 mg/kg galidesivir + 20 mg lidocaine) on Day 4 of Part 3 after the subject 
experienced nausea, vomiting, and abdominal pain, the Investigator made the decision to 
discontinue the subject due to an intercurrent illness (injection anxiety).   


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The primary TEAE reported by subjects randomized to galidesivir was injection site pain; 
injection site pain was reported more often by subjects receiving galidesivir without lidocaine 
(Part 1: 13 subjects [36.1%] and Part 2: 10 subjects [66.7%]) vs. subjects receiving galidesivir 
with lidocaine (Part 2: 2 subjects [12.5%] and Part 3: 5 subjects [21.7%]). Investigator-assessed 
erythema, swelling, pain, and tenderness were infrequently reported, with little or no evidence of 
a dose relationship.   
A Grade 2 TEAE (injection site pain) definitely related to galidesivir was reported by 6 subjects 
randomized to 4.0 mg/kg galidesivir alone in Part 2. Two subjects experienced Grade 2 TEAEs 
possibly related to galidesivir: liver enzyme elevation (ALT, Part 2: 4.0 mg/kg galidesivir alone) 
and nausea, vomiting, and abdominal pain (Part 3: 10.0 mg/kg); the events resolved. As was 
expected with IM administration, Grade 2 and 3 treatment-emergent CK abnormalities were 
reported in all three parts of the study; however, these CK abnormalities were observed more 
often in subjects who received higher galidesivir doses administered without lidocaine. Four 
subjects from Part 1, Cohort 4 experienced Grade 2 or 3 elevations in potassium. A safety 
evaluation of the potassium elevations found the elevations not to be associated with clinical 
evidence of hyperkalemia; there were no ECG changes at time points that coincided with the 
elevated results, and the subjects were clinically well with no TEAEs at these time points. It was 
determined that the elevated potassium values were likely due to pseudohyperkalemia.      
No clinically significant dose-related trends in laboratory values, vital signs, ECGs, or ECHOs 
were noted. 
4.4. 
Rationale for Study 
Galidesivir is being developed as a parenterally administered nucleoside analog antiviral drug 
designed to inhibit the activity of a range of viruses associated with high morbidity or mortality, 
including MARV by disrupting formation of viral RNA by virally-encoded RNA-dependend 
RNA polymerase enzyme (RdRp). Galidesivir shows concentration-dependent inhibition of viral 
replication in mammalian cell lines in vitro (Warren, Wells et al. 2014).   
Study BCX4430-101, as described in Section 4.3.1, evaluated the exposure of galidesivir 
following single and multiple dose administration by IM injection. With the IM route of 
administration, in order to give doses over 10 mg/kg, subjects will have to be given more than 4 
injections per day.  The IV infusion route of administration will allow the administration of 
higher doses of galidesivir without numerous injections.  This is important because the target 
population for this drug are patients with bleeding tendencies due to viral hemorrhagic fever.   
This Phase 1 study will evaluate the exposure to galidesivir (plasma drug levels) achieved with a 
range of doses after administration by IV infusion over 60 minutes, will identify a safe dose 
range of galidesivir administered after a single dose, and will assist in evaluating the therapeutic 
window of galidesivir.  Additionally, this study will provide information about exposure of 
galidesivir for future studies with multiple dose administration.  
4.4.1. 
Study and Population 
Healthy subjects have been selected to minimize variability in factors that may affect the safety, 
tolerability, and PK profile of galidesivir. In MVD outbreaks, both sexes are affected; therefore, 
both men and women will be enrolled in the study.  It is considered imperative to characterize 
the safety and PK of galidesivir in women, including those of reproductive age, at this early stage 


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of development, and therefore considered acceptable to include women in this study, using the 
strict contraception requirements that are specified in Section 8.1. Both genders will be enrolled 
in the study. 
Reproductive toxicology studies have been conducted (Section Section 4.2.3).  Women of 
childbearing potential may be enrolled in this study if they meet the contraceptive and pregnancy 
test requirements listed in the inclusion and exclusion criteria. 
4.4.2. 
Rationale for Route of Administration 
In nonclinical experiments, galidesivir plasma exposures (AUC) after IM and IV bolus 
administration were very similar in mice, rats, and cynomolgus monkeys, with 
concentration-time profiles that were nearly superimposable comparing the two routes across 
species. Additionally, exposure following IV and IM administration was largely dose 
proportional in nonclinical species. Although both IM and IV administrations are theoretically 
feasible routes of administration for galidesivir, based on the effective dose in NHP models of 
filovirus diseases, the solubility profile of galidesivir requires that multiple daily IM injections 
would be needed for treatment of MVD and other viral hemorrhagic fevers.  The IV route of 
administration may be more useful for outbreak situations, because it will require fewer needle 
sticks than multiple IM injections, thus helping to reduce the risk of needle-stick transmission of 
filovirus infection to health care providers. Therefore, the IV route of administration is being 
explored in this study. 
4.4.3. 
Rationale for Study Doses 
The initial dose levels for galidesivir in this study were selected on the basis of the PK and safety 
data from Study BCX4430-101 together with target exposures effective in animal models of 
MVD. The PK of galidesivir was well characterized in Study BCX4430-101 after both single 
and multiple ascending doses; this enabled the dose selection for this study to be made on the 
basis of simulated efficacious exposures in models of MVD and other filovirus infections.  The 
simulations of MVD model efficacious exposures were based on pharmacokinetic studies in 
cynomolgus macaques and corresponding effective doses in the same species in a model of 
MVD.  Simulations of human exposure after IV infusion administration have suggested that 
exposure will be similar to the observed following the IM administration of galidesivir.  The 
5 mg/kg dose selected as the starting dose for this study is anticipated to have a Cmax of 
approximately 3000 ng/mL and an AUC from time 0 to 24 hours (AUC24) of approximately 
10,000 ng.h/mL.  The proposed maximum dose for this study, a single dose of 20 mg/kg, is also 
supported by the nonclinical safety and TK data for IV administration in monkeys and rats, with 
a no adverse effect level (NOAEL) in monkeys of 30 mg/kg/day with an associated AUC24 of 
52,500 ng.h/mL; the expected human exposure at a 20 mg/kg dose is approximately 
47,000 ng.h/mL. 
All planned proposed doses for the study are in Section 7.1. The choice of higher doses to be 
studied may be modified depending on emerging PK results from the lower dose cohorts.   
4.5. 
Benefit-Risk Analysis 
Galidesivir is a parenterally available small molecule nucleoside analog inhibitor of viral RNA 
polymerase activity, mediated through non-obligate RNA chain termination. Nucleoside analogs 


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have a proven mode of action in the treatment of multiple human viral infections. As a class, 
some nucleoside analogs have been associated with serious adverse reactions, including 
peripheral neuropathy, myopathy, pancreatitis, and lactic acidosis with hepatic steatosis, 
resulting from mitochondrial toxicity following chronic dosing (Lund, Peterson et al. 2007). 
There is no evidence in the literature of acute severe adverse reactions resulting from treatment 
with nucleoside analogs following single doses or up to 1 week of dosing. 
• Toxicity studies in the cynomolgus monkey and rat have been conducted with IV 
infusion administration. Although Cmax and AUC are lower following IV infusion 
compared with IM injection, no new findings have been identified from IV infusion 
toxicology studies. Therefore, the IM studies provide useful toxicological information 
to develop appropriate monitoring in an IV study. 
• Toxicology studies in rats and monkeys summarized in the IB suggest that the 
primary target organs of galidesivir toxicity following IM administration in the rat 
were the kidney and liver, with toxicities also observed in the spleen, testes, thymus, 
heart, hematopoietic system, and injection sites. Target organs of systemic toxicity in 
the monkey were kidney, liver, lymphoid system, and injection sites. The principal 
target organ of systemic toxicity in rats and monkeys following IV infusion was the 
kidneys (Section 4.2.3). Microscopic changes in liver and kidney correlated to 
monitorable changes in relevant clinical chemistry analytes and were reversible. The 
large intestine was also a target in rats at the highest dose examined; minimal-to-mild 
single cell necrosis/degeneration in the cecum (with colon and rectum less frequently 
affected), with or without concurrent mucosa crypt epithelium 
hyperplasia/hypertrophy and/or mucosa inflammation. Galidesivir is compatible with 
human blood and does not cause hemolysis at concentration up to and including 15 
mg/mL.   
• Clinical chemistry monitoring will be conducted as part of the safety assessments in 
this study and will include neutrophil gelatinase-associated lipocalin (NGAL), a novel 
marker for tubular injury, and cystatin C, a biomarker of renal function. The 
lymphoid system is monitorable via routine blood counts. Testosterone levels will be 
monitored in male subjects.  Although the risk of cardiomyopathy is not clear from 
animal studies, this study will use laboratory (creatine kinase MB fraction [CK-MB], 
troponin I), ECG (both 12-lead and telemetry), and radiographic (ie, ECHOs) 
methods to assess and monitor cardiac health.  
• Secondary and safety pharmacology studies summarized in the IB suggest that 
galidesivir has a low potential to lead to unwanted cellular toxicities or effects in key 
mammalian functions, such as respiratory, central nervous system, or 
electrocardiology. Increases in BP and heart rate were observed at IM doses 
> 10 mg/kg in nonclinical studies in conscious monkeys. Subjects with hypertension 
will be excluded from the study, and subjects who are enrolled will be monitored for 
vital signs in addition to the assessments of cardiac health mentioned above.   
Given the above considerations, there appears to be a relatively low risk of severe adverse 
reactions resulting from single dose administration of galidesivir. All cohorts will rely upon the 
use of sentinel dosing (1 subject receives active drug and 1 subject receives placebo until the 


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acute safety profile of the investigational drug can be defined). Appropriate safety monitoring for 
observed nonclinical safety risks will be employed.   
4.5.1. 
Risks/Safety Signals Observed in the First-in-Human Intramuscular Injection 
Study with Galidesivir 
In Study BCX4430-101, healthy volunteers received IM injections of galidesivir, with 6 single 
ascending dose (SAD) cohorts ranging from 0.3 to 10 mg/kg, and 4 multiple ascending dose 
(MAD) cohorts (2.5, 4.0 and 10 mg/kg once daily [QD] x 7 days). Subjects received one to four 
injections, depending on dose.  
• In the SAD cohorts, none of the nonclinical toxicology safety risks were confirmed as 
clinical safety signals.  
• The most common adverse events (AEs) were injection site pain (13/48 subjects 
[27.1%]), headache (8/48 [16.7%]), and presyncope (3/48 [6.3%]). No other AEs 
were reported in more than a single subject.  
• No significant laboratory abnormalities were noted, although there were several 
instances of pseudohyperkalemia. These elevated potassium levels were not 
confirmed upon retest and had no associated symptoms or ECG changes and were 
determined to be laboratory artifact.  
• There were no changes in cardiac enzymes, ECGs, or ECHOs.  
The second part of the study evaluated lidocaine co-administration with galidesivir IM 
injections. 
• In the lidocaine 4.0 mg/kg BCX4430 single dose cohort, none of the nonclinical 
toxicology safety risks were confirmed as clinical safety signals. 
In the MAD portion of the study, subjects received 2.5, 5.0 and 10.0 mg/kg of galidesivir along 
with 20 mg lidocaine in each injection intramuscularly for 7 days. Subjects received 1 to 4 
injections daily in order to deliver the complete dose. 
• In the MAD cohorts, none of the nonclinical toxicology safety risks were confirmed 
as clinical safety signals.  
• The most common AEs were injection site pain (5 subjects [17.2%]), injection site 
discomfort (2 [6.9%]), injection site reaction (2 [6.9%]), vessel puncture site bruise 
(2 [6.9%]), and headache (3 [10.3%]). No other AEs were reported in more than a 
single subject.  
• No significant laboratory abnormalities were noted other than CK elevations 
consistent with multiple IM injections. In a few subjects, the elevated CK was 
accompanied by mildly elevated CK-MB without any evidence of cardiac injury, and 
mildly elevated aspartate aminotransferase (AST), also consistent with IM injections. 
Also noted were subjects in all 3 MAD cohorts with activated partial thromboplastin 
time (aPTT) and prothrombin time abnormalities. In Cohort 3, 1 subject had Grade 3, 
6 subjects had Grade 2, and 1 subject had Grade 1 aPTT abnormalities. In 4 of 8 
subjects, the prothrombin time was also abnormal. In most cases there was no 
international normalized ratio abnormality and no subject had any clinical symptoms 


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or bleeding. These results were considered not clinically significant and the cause was 
considered to be laboratory artifact.  
Overall, no safety risks were identified during the Phase 1 study with galidesivir IM injection 
other than injection site pain, which will not be a concern during IV administration of galidesivir. 
Given the lack of any injection site changes, such as significant erythema, edema, nodules, 
necrosis, after IM injection, extravasation of galidesivir infused IV is unlikely to cause injury; 
however, infusion sites will be closely monitored.  
4.5.2. 
Risks of Potential Adverse Events with Study-Mandated Procedures 
Blood will be drawn from study participants for safety and PK assessments, which imparts a 
small risk of venipuncture injury, infection, and hypotension. To reduce the risk of anemia, 
< 500 mL of blood will be drawn from any subject during the study (screening through last 
scheduled follow-up visit), and anemic subjects will not be allowed to enroll in the study or 
continue participation if they become anemic during the study. The total blood collected for this 
study for both PK and safety laboratory assessments will be approximately 300 mL.   
Venipuncture may cause transient discomfort and may result in fainting. Fainting is usually 
transient and managed by having the subject lie down and elevate his/her legs. Bruising at the 
site of the venipuncture may occur but may be prevented or lessened by applying pressure to the 
site for several minutes. Venipuncture may also cause infection. The use of aseptic (sterile) 
technique will make infection at the site where blood will be drawn extremely unlikely. 
4.5.3. 
Risks Associated with Infusions 
Galidesivir at a concentration of 100 mg/mL will be diluted to a maximum concentration of 
5 mg/mL using an LR solution. IV doses of galidesivir will be infused over 60 minutes via an IV 
catheter at a maximum rate of 8.33 mL/min. Nonclinical local tolerability studies in the rabbit 
showed that intra-arterial injection of 30 mg/kg and perivascular injection of 7.5 mg/animal 
caused severe erythema with no microscopic correlate. In Study BCX4430-101, there were no 
injection site changes such as erythema, edema, nodules, necrosis, etc., after IM injection. Taken 
together, these findings indicate that it is unlikely that extravasation of galidesivir-infused IV 
would cause injury; however, infusion sites will be closely monitored.  
The pH of the diluted drug in LR that will be infused will be approximately 4.0 to 5.0 (Alcami 
2016), which should buffer to a physiologic pH rapidly, making peripheral veins appropriate for 
infusion. General risks associated with IV infusions include pain, bruising, phlebitis, thrombosis 
of the cannulated vein, and leaking IV fluid into the tissues near the injection. Careful inspection 
of the site, including visualization of blood return at the catheter site and an infusion time of 
60 minutes (ie, maximum rate of 8.33 mL/minute), will minimize this risk. There is a risk of 
infection; however, this is a small risk as aseptic technique will be employed to reduce this risk.  
4.5.4. 
Known Potential Benefits 
Apart from receiving a medical assessment during the screening process, there is no benefit to 
the subjects from taking part in this study. The development of galidesivir may be of benefit to 
the broader population as a potential therapeutic medical countermeasure for the treatment of 
MVD and other filovirus infections.  


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5. 
STUDY OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
• To evaluate the safety and tolerability of SAD of galidesivir administered by IV 
infusion in healthy subjects 
5.2. 
Secondary Objectives 
• To characterize the plasma PK profile and urinary elimination of SAD of galidesivir 
administered by IV infusion in healthy subjects 
6. 
ENDPOINTS 
6.1. 
Primary Endpoints 
• Safety and tolerability parameters including AEs and SAEs, laboratory abnormalities, 
vital signs, ECGs, ECHOs, cardiac telemetry, and PE findings 
6.2. 
Secondary Endpoints 
• Plasma and urine PK parameters for galidesivir 
• Dose proportionality of galidesivir 
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This SAD study will evaluate the safety, tolerability, and PK of single doses of galidesivir vs. 
placebo administered as IV infusions in healthy subjects in up to four dose cohorts. A single dose 
of study drug will be administered to 8 subjects per cohort: 6 subjects will receive galidesivir IV, 
and 2 subjects will receive matching placebo.   
The planned cohorts are as follows: 
• Cohort 1, Regimen A: 5 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• Cohort 2, Regimen B: 10 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• Cohort 3, Regimen C: 15 mg/kg galidesivir or placebo, IV infusion × 1 dose 
• Cohort 4, Regimen D: 20 mg/kg galidesivir or placebo, IV infusion × 1 dose 
Study drug will be infused IV via a calibrated infusion pump over 60 minutes at a maximum rate 
of 8.33 mL/min. 
As a safety precaution, on the first day of dosing in all cohorts, only 2 subjects will be dosed (to 
be referred to as sentinel subjects). The randomization schedule will be constructed such that 1 of 
the sentinel subjects dosed on the first day will be randomized to receive galidesivir and 1 will be 
randomized to receive placebo. The remainder of the cohort (5 subjects receiving galidesivir: 


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1 receiving placebo) will be dosed at least 2 days after the sentinels, contingent upon satisfactory 
results from safety assessments of the sentinel subjects. 
Following a screening period to determine eligibility, subjects in each cohort will be admitted to 
the clinical research unit (CRU) on Day -1. Study eligibility will be confirmed upon admission to 
the CRU, and subjects will remain in the CRU overnight prior to dosing on Day 1. Following 
administration of the study drug on Day 1, subjects will remain in the CRU for 96 hours to 
enable collection of PK samples and safety and tolerability data. Subjects will be discharged 
from the CRU on Day 5, 96 hours after the start of the infusion. Subjects will return to the CRU 
for PK samples on Day 6 (+1 day), Day 8 (+1 day), and Day 14 (± 1 day). Subjects will return to 
the CRU for a final follow-up visit on Day 21 (+ 2 days). The study design is shown in Figure 1. 
In the event that there are any unresolved safety findings that are ongoing at Day 21, the subject 
will be followed at additional study visits until the findings are resolved or stabilized. If it is 
determined that the median half-life is longer than anticipated following IV infusion, or if after 
obtaining PK data through 96 hours, the AUCinf estimate is > 25% of the AUC from time 0 to the 
last measurable concentration of drug (AUClast), serial PK sampling may be extended beyond 
96 hours in subsequent cohorts, or additional samples may be added in the intervening period 
between discharge from the CRU and the final follow-up visit (Day 21).  
Safety and tolerability will be evaluated through assessments of AEs, laboratory analyses 
(clinical chemistry, hematology, coagulation, urinalysis, CK-MB, troponin), vital signs, ECGs, 
ECHOs, cardiac telemetry, and PEs at the time points indicated in the schedule of assessments. 
PK parameters will be analyzed from the plasma and urine samples collected at the time points 
indicated in the schedule of assessments (Table 5).  
Enrollment of subjects in each sequential higher dose level cohort will occur only after 
completion of a clinical safety review of laboratory, AE, vital sign, ECG (12-lead and telemetry), 
and PE data for all subjects up through 96 hours post-dose and plasma PK data through 24 hours, 
by the Sponsor medical monitor, clinical pharmacologist, and principal investigator (PI) at a dose 
escalation review meeting. Rules for halting the escalation to the next dose will be followed as 
defined in Section 7.6.3.2.   
Safety and PK data for each cohort will be submitted to the US Food and Drug Administration 
(FDA) after each cohort is complete. Escalation to the next planned dose may proceed as long as 
the halting rules are not triggered as defined in Section 7.6.3.2.   


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Figure 1: 
BCX4430-106 Study Design 
 
 
 
Abbreviations: D = day; PK = pharmacokinetic.  
 


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Table 5: 
Schedule of Assessments 
Assessment 
Screening 
In Clinic (CRU) Study Period 
Return to 
CRU for PK 
Sample 
Follow-up or 
Early 
Termination 
Visit 
Day −28  
to −2 
Day −1 
(Admission) 
Day 1 
Baseline  
(Pre-
dose) 
Day 1 
(Post 
dose) 
Day 2 
Day 3 
Day 4 
 
Day 5 
(Discharge 
Day 6, Day 
8, Day 14n 
Day 21 + 2  
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusio
n 
criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
Weight/height/BM
I 
X 
Xa 
 
 
 
 
 
 
 
 
Drugs of abuse 
screen/urine 
alcohol test/urine 
cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
HIV/HCV/HBV 
serology 
X 
 
 
 
 
 
 
 
 
 
Physical 
examinationb 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
Xc 
 
Xc 
Xd 
Xd 
Xd 
Xd 
Xd 
 
Xd 
Cardiac telemetry 
 
 
Xe 
Xe 
 
 
 
 
 
 
ECHOf 
Xf 
 
 
 
 
Xf 
 
 
 


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Assessment 
Screening 
In Clinic (CRU) Study Period 
Return to 
CRU for PK 
Sample 
Follow-up or 
Early 
Termination 
Visit 
Day −28  
to −2 
Day −1 
(Admission) 
Day 1 
Baseline  
(Pre-
dose) 
Day 1 
(Post 
dose) 
Day 2 
Day 3 
Day 4 
 
Day 5 
(Discharge 
Day 6, Day 
8, Day 14n 
Day 21 + 2  
 
Vital signs 
X 
X 
Xg 
Xg 
Xg 
X 
X 
X 
 
X 
Pregnancy testh 
X 
X 
 
 
 
 
 
 
 
X 
FSHi 
X 
 
 
 
 
 
 
 
 
 
Clinical chemistry/ 
hematology 
X 
Xm 
 
X 
X 
X 
X 
X 
 
X 
Urinalysis 
X 
Xm 
 
 
X 
X 
X 
X 
 
X 
aPTT/PT 
X 
Xm 
 
 
 
 
 
X 
 
X 
Testosteronej 
 
Xm 
 
 
 
 
 
X 
 
X 
Troponin I 
 
Xm 
 
 
 
 
 
X 
 
X 
CK-MB 
 
Xm 
 
 
 
 
 
X 
 
X 
Cystatin C and 
NGAL 
 
Xm 
 
 
 
 
 
X 
 
X 
UACR 
X 
Xm 
 
 
 
 
 
X 
 
X 
Plasma for 
galidesivir PK 
analysisk 
 
 
Xk 
Xk 
X 
X 
X 
X 
X 
X 
Urine for 
galidesivir PK 
analysisl 
 
 
X 
X 
X 
X 
X 
X 
 
 
AE assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug dosing 
 
 
 
X 
 
 
 
 
 
 


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Abbreviations: AE = adverse event; aPTT = activated partial thromboplastin time; BMI = body mass index; CK-MB = creatine kinase-MB; CRU = clinical 
research unit; ECG = electrocardiogram; ECHO = echocardiogram; FSH = follicle-stimulating hormone; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV 
= human immunodeficiency virus; NGAL = neutrophil gelatinase-associate lipocalin; PK = pharmacokinetic; PT = prothrombin time; UACR = urine 
albumin-to-creatinine ratio. 
a. 
Weight only. 
b. 
A physical examination consisting of the head and neck, skin, chest (lungs and heart), abdomen (gastrointestinal tract, liver, spleen and kidneys), back, 
musculoskeletal system, and neurologic system should be conducted at screening and on Day 5 prior to discharge. Breast and genitourinary system do not 
require examination unless the potential subject indicates a complaint or comorbidity that could result in exclusion.  All other physical exams will be 
symptom directed. The site of infusion should be checked for any changes in skin.   
c. 
Three (3) serial ECGs will be performed at screening and baseline 1–3 minutes apart. Pre-dose ECG should be collected within ≤ 2 hours of the first dose. 
d. 
12-lead ECGs will be conducted on Day 1 at 2 and 4 hours post dose (post start of the infusion) and on Day 2 at 24 hours post dose (post start of the 
infusion). An acceptable window is ± 10 minutes from the nominal time point. All subsequent ECGs are daily.  
e. 
Cardiac telemetry will be initiated ≥ 2 hours prior to administration of the dose and will continue for 24 hours after the infusion is started. Subjects may be 
disconnected for bathroom, hygiene needs, and for 20-minute periods 3 times a day for meals. In addition, subjects may be disconnected for 10 minutes 
every 2 hours while awake for mild physical exercise such as walking or calf exercises.  
f. 
The ECHO may be performed at any time from screening to Day -2 for eligibility determination. An ECHO should also be performed on Day 4. An 
acceptable window for the Day 4 ECHO is up until Day 5 discharge. 
g. 
Vital signs (except temperature) will be obtained pre-dose (within 2 hours of dosing) 1, 2, 4, and 8 hours post dose (post start of the infusion) on Day 1, at 
24 hours post dose on Day 2 and once per day where indicated. Oral temperature will be obtained at 8 hours post dose on Day 1 and at 24 hours post dose 
on Day 2. Subjects should be rested for 10 minutes in the supine position prior to vital sign measurements.  All times are from the start of the infusion. 
h. 
A serum pregnancy test will be administered at screening to all women; all other pregnancy tests performed during the study may be urine pregnancy tests. 
i. 
An FSH level will be measured in women who report that they have been postmenopausal ≤ 2 years. 
j. 
Free testosterone will be measured in male subjects. 
k. 
Plasma for PK galidesivir analysis will be collected pre-dose, 30 min (halfway through the infusion), 1 h (end of the infusion), 1.25 h, 1.5 h, 2 h, 3 h, 4 h, 6 
h, 8 h, 10 h, 12 h,16 h, 24 h, 36 h, 48 h, 60 h, 72 h, and 96 h following the start of the infusion. The pre-dose PK sample must be collected within ≤ 1 hour 
of the dose. Assessment windows around each PK draw will be ± 2 minutes for sampling times up to 2-hour post dose and from 2-hour post dose onward, 
± 10 minutes while subject is confined in the unit. All sample times are from the start of the infusion.   
l. 
For the analysis of urinary excretion of galidesivir, an aliquot of urine will be collected pre-dose (0 hour) and all urine will be collected for the following 
post dose intervals: 0–12 hours, 12–24 hours, 24–48 hours, 48–72 hours, and 72–96 hours. All sample times are from the start of the infusion.   
m. 
Baseline for study post dose comparisons. NGAL, cystatin C, UACR, testosterone, troponin I, and CK-MB can be collected on Day -1 or Day 1 (pre-dose). 
n. 
Subjects will return to the CRU to have a plasma PK sample collected on Day 6 (+1), Day 8 (+1), and Day 14 (±1). This visit is intended to be a short visit 
(approximately 1-2 hours) and can take place at any time during the specified window.  A plasma PK sample will also be collected at the follow-up visit on 
Day 21. 
  
 


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7.2. 
Number of Subjects 
It is planned that 32 subjects will be enrolled in the study, with 8 subjects enrolled per cohort. In 
each cohort, 6 subjects will receive galidesivir and 2 subjects will receive placebo.   
Subjects may be replaced as noted in Section 8.5. 
7.3. 
Treatment Assignment 
Following confirmation of eligibility, subjects will be identified by a unique 5-digit subject 
identifier (eg, 11001) in which the first digit indicates the study site identifier, the second digit 
indicates the cohort number and the final 3 digits indicate the subject number. Any replacement 
subjects will be identified by replacing the third digit “0” with “9”. For example, if 
Subject 11005 withdraws from the study early, the replacement subject will be numbered 11905 
and will receive the same study treatment (ie, active or placebo) as Subject 11005. 
Subject numbers will be as follows:  
Cohort 
Subject Numbers 
Replacement Subject Numbers 
1 
11001 to 11008 
11901 to 11908 
2 
12001 to 12008 
12901 to 12908 
3 
13001 to 13008 
13901 to 13908 
4 
14001 to 14008 
14901 to 14908 
7.4. 
Randomization Procedures 
The randomization schedules will be generated by an unblinded study statistician. Masking 
procedures will be as outlined in Sections 7.5 and 9.6 and will be used to blind study drug.   
A computer-generated randomization schedule will be used to randomly assign subjects to 
galidesivir or placebo. Subjects in each of the Cohorts 1 to 4 will be randomized to galidesivir or 
placebo in a 3:1 ratio (ie, 6 subjects per cohort will be randomly assigned to receive galidesivir 
and 2 subjects per cohort will be randomly assigned to receive placebo). 
As a safety precaution, on the first day of dosing in all cohorts, 2 sentinel subjects will be 
initially dosed. The randomization schedule will be generated so that in each cohort 1 sentinel 
subject is randomly assigned to receive galidesivir and 1 is randomly assigned to receive 
placebo. Contingent upon satisfactory results as determined by the PI from safety assessments 
24 hours post-dosing (e.g., AEs, ECGs, etc. as described in Section 7.6) of the sentinel subjects, 
the remainder of the cohort may be dosed at least 2 days later (with 5 subjects randomly assigned 
to receive galidesivir and 1 subject randomly assigned to receive placebo). 
7.5. 
Masking Procedures 
This is a double-blind study; treatment assignment within a cohort will be blinded to the PI, 
clinical staff, study subjects, and the data management team, with the exception of the unblinded 


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dosing team, if required. As described in Section 9.6, once infusion bags are prepared and 
labeled, the research pharmacist will mask the IV bag and tubing (ie, with the use of an overlay 
or masking tape) to blind the color of the solution in the IV bag and in the IV line. 
An unblinded dosing team may be utilized in this study if required.  Members of the unblinded 
dosing team will not be involved in any assessments on the study and will only be utilized for 
dose administration.    
The PI or designee(s) will confirm subject eligibility. The unblinded pharmacist at the clinical 
site will receive a copy of the final randomization schedule from the unblinded statistician for 
preparation of the study drug. The laboratory performing bioanalytical analysis will also be 
provided this randomization scheme. The clinical pharmacologist will receive a copy of the 
randomization scheme to prepare interim PK summaries for dose escalation review meetings. 
The unblinded clinical pharmacologist will attend all dose escalation review meetings. 
Prior to database lock and unblinding, all original randomization materials will be held by 
quality assurance personnel and blinded staff will not have access to the randomization schedule 
during this time. Disclosure envelopes are held in a locked cabinet in the clinical unit and will be 
used in the event of an emergency by the PI.  
Access to study drug assignment will be immediately available if the PI deems it necessary to 
break the study blind in the interest of a subject’s medical safety, in case of a medical 
emergency, to meet regulatory safety reporting obligations, or if warranted during scheduled 
safety reviews. The PI must contact the medical monitor within 24 hours following disclosure of 
study drug assignment.  
Any request for information on the randomization schedule after initial issue must be made using 
a randomization disclosure form, except in the case of emergency unblinding, which must be 
recorded on the emergency unblinding form. Details of any disclosure of the randomization 
schedule will be documented and filed appropriately.  
Breaking the blind for a single subject (or the 2 sentinel subjects) will not affect the blind for the 
remaining subjects; however, the site must appropriately document the process. Data may be 
unblinded, if required, for an interim review of PK and safety data. 
7.6. 
Dose Escalation and Continuation Criteria 
7.6.1. 
Criteria for Continuing to Dose Within a Cohort after Sentinel Subjects Have 
Been Dosed 
In each cohort, 2 sentinel subjects will be dosed initially. The randomization schedule will be 
constructed such that 1 of the sentinel subjects dosed on the first day will be randomized to 
receive galidesivir and 1 will be randomized to receive placebo. After review of the safety data 
from the 24-hour post-dose period for the sentinel subjects, which includes review of any AEs, 
any abnormalities in the bedside ECGs, safety laboratory assessments and vital signs, the 
remainder of the cohort (5 subjects randomized to galidesivir; 1 randomized to placebo) will be 
dosed at least 2 days after the sentinel subjects.   


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7.6.2. 
Dose Escalation Criteria  
As described in Section 11.5.2, at the completion of each cohort, the Dose Escalation Committee 
(DEC) will meet to review the safety and PK data from the cohort. Dose escalation to the 
subsequent cohort may proceed without consult with the Safety Monitoring Committee (SMC) as 
long as none of the following criteria are met: 
• One or more subjects with a treatment-emergent QT interval corrected by Fridericia's 
formula (QTcF) > 480 ms (Grade 2 per the National Institutes of Health [NIH] 
Division of Microbiology and Infectious Diseases [DMID] scale) as determined from 
bedside ECGs (with repeat ECG). If this occurs, the SMC may consult with an 
independent cardiologist as needed.  If it is deemed acceptable to restart the study 
following review of the data and discussion with an independent cardiologist, if 
needed, dosing may resume. 
• One or more subjects experiences an increase in BP that requires acute treatment, or 
has a confirmed systolic BP > 160 mmHg, or a confirmed diastolic BP > 100 mmHg 
(Grade 3 per DMID scale). Confirmed BP changes require at least 2 measurements at 
least 2 hours apart, each measured after at least 5 minutes of supine rest. 
• Anaphylactic reaction occurs in 1 subject. 
• One or more subjects experience a similar Grade 3 treatment-emergent laboratory 
abnormality or AE that is suspected to be drug-related as determined by the 
Investigator. 
• One subject experiences an SAE. 
• A cohort’s median AUC24 is ≥ 52,500 ng.h/mL, equivalent to the NOAEL exposure 
in cynomolgus monkeys.   
If one of the above safety criteria are met, the SMC will be called to review the safety data from 
the study. The SMC may make one of two recommendations: to halt the study for further review, 
or to modify the planned dose escalation to the next dose level. Additionally, the dose escalation 
may be modified based on review of emerging PK data from any cohort, if needed, in order to 
refine the escalation to achieve exposure that will not exceed the NOAEL. This review of data 
may include modeling of planned doses to predict exposure from subsequent cohorts.   
7.6.3. 
Study Drug and Study Halting Rules 
7.6.3.1. 
Infusion Halting Rules 
For any individual subject, an infusion must be stopped for the following non-drug related 
events: the IV line is lost, there is extravasation, or the IV pump malfunctions such that the dose 
cannot be given in a controlled manner.  A 10-minute window is allowed for the infusion, in 
order to allow for infusion issues to be resolved.   
For any individual subject, the infusion must be stopped for any suspected drug-related event 
such as hypersensitivity (Grade 1 or higher) during infusion.  
For any individual subject, the infusion must be stopped for any suspected severe (Grade 3) or 
serious adverse event during infusion. 


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The reason for subject discontinuation from the infusion will be recorded in the source 
documents and electronic Case Report Form (eCRF). In all cases, subjects who discontinue study 
drug should remain in the study and have all protocol defined study safety assessments 
performed.  
7.6.3.2. 
Study Halting Rules 
Further dosing of other subjects in any cohort will be halted if any of the following criteria are 
met cumulatively across cohorts; dosing may not recommence unless recommended by the study 
SMC during the SMC review process: 
• The death of a dosed subject for any reason. 
• One galidesivir-treated subject experiences an SAE that is considered to be at least 
possibly related to study drug.   
• Two or more subjects experience a Grade 3 AE in the same organ class (systemic 
toxicity, confirmed clinical laboratory tests, or vital signs) regardless of relatedness to 
study drug. 
• An anaphylactic reaction occurs in 2 subjects. 
• One or more subjects experience a confirmed Grade 3 QTcF (QTcF > 500 ms or 
QTcF increase > 60 ms), or two or more subjects cumulatively have experienced a 
Grade 2 change in QTcF (>480 msec). If following discussion with an independent 
cardiologist, it is deemed acceptable to restart the study, dosing will resume. All 
relevant data will be submitted to the regulatory authorities and Institutional Review 
Board (IRB).   
• Two or more subjects experiences an increase in BP which requires acute treatment, 
or has a confirmed systolic BP > 160 mmHg, or a confirmed diastolic BP 
> 100 mmHg. Confirmed BP changes require at least two measurements at least 
2 hours apart, each measured after at least 5 minutes of supine rest. 
If, following review by the SMC (Section 11.5.3) it is deemed acceptable to restart the study, all 
relevant data will be submitted to the regulatory authorities and the IRB. 
7.7. 
Criteria for Study Termination 
BioCryst reserves the right to terminate the study prior to inclusion of the intended number of 
subjects but intends only to exercise this right for valid scientific or administrative reasons. Valid 
scientific reasons may include the development of unacceptable safety or PK findings that do not 
support continuation of the study. After such a decision, the PI must contact all ongoing subjects 
immediately after notification. As directed by BioCryst, all study materials must be collected and 
all (eCRFs completed to the greatest extent possible. Subjects enrolled at the time of study 
termination would continue to undergo all scheduled assessments as defined in Section 10.   
After the start of protocol activities but prior to the commencement of dosing, the study may be 
terminated by the Sponsor or PI without consultation with the FDA and IRB. Notification of 
early termination should be provided to the FDA and IRB within 15 days, clearly explaining the 
reasons for the termination. 


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If the study is abandoned prior to commencement of any protocol activities, the PI or Sponsor 
must notify the FDA and IRB by letter outlining the reasons for abandonment of the study. 
Once dosing has begun, the study will be completed as planned unless the following criteria are 
satisfied that require early termination of the study: 
• Study halting rules are met and continuing the study would pose an unreasonable risk 
to subject safety. 
• New information regarding the safety of the investigational medicinal product (IMP) 
that indicates an unreasonable risk for subjects participating in the study. 
• Significant violation of Good Clinical Practice (GCP) that compromises the ability to 
achieve the primary study objectives or compromises subject safety. 
If it becomes necessary to consider termination of the study after dosing has begun, dosing may 
be suspended pending discussion between the Sponsor and PI. Dosing may be suspended 
immediately on safety grounds. 
The study may be terminated or suspended at the request of the FDA, SMC, National Institute of 
Allergy and Infectious Diseases (NIAID), or IRB. 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study: 
1. Able to provide written, informed consent.  
2. Males and non-pregnant, non-lactating females aged 18–55 years.  
3. BMI of 19.0 to 32.0 kg/m2, inclusive.  
4. Subject weight ≥ 50 kg (110 lb.) and ≤ 100 kg (220 lb.). 
5. Contraception requirements: 
 
All female subjects must have a negative serum pregnancy test at screening and a 
negative urine test at Day -1 upon admission to the CRU.  Female subjects must meet one 
of the following requirements: 
 
a. If the female subject is of childbearing potential, she must agree to practice 
abstinence, exclusively have female partners, or use acceptable contraception during 
the study and for 30 days after the infusion ends on Day 1. 
 
Note: a woman is considered of child bearing potential unless post-menopausal (without menses) for 
(> 2 years, postmenopausal for ≤ 2 years and has a follicle-stimulating hormone (FSH) >40 mIU/mL at 
the screening visit, or surgically sterilized via bilateral oophorectomy, or hysterectomy or bilateral 
tubal ligation or successful Essure placement with documented confirmation test at least 3 months after 
the procedure. 


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Note:  Acceptable contraception methods are restricted to the following: an intrauterine device (IUD) 
or intrauterine system (IUS) (implanted any time prior to or during screening), any form of hormonal 
contraception, use of male or female condom with or without spermicidal 
foam/gel/film/cream/suppository, use of an occlusive cap (diaphragm, or cervical/vault caps) with 
spermicidal (foam/gel/film/cream/suppository), or monogamous relationship with a vasectomized 
partner. 
 
b. If the female subject reports being postmenopausal for ≤ 2 years and has a FSH 
≤ 40 mIU/mL at screening visit, she must agree to using acceptable contraception (as 
proposed above) during the study and for 30 days after the infusion ends on Day 1. 
Female subjects with a FSH > 40 mIU/mL and history of being postmenopausal 
≤ 2 years will not be considered to be of childbearing potential. 
Male subjects must comply with the following requirements through the study and for 
90 days post dose:  
a. If the male subject has female partners of childbearing potential, he must agree to not 
father a child by using at least one acceptable effective contraceptive method as 
defined above.  
b. Male subjects who declare themselves as sexually abstinent or who exclusively have 
male partners do not have to comply with contraceptive requirements.  
c. Male subjects will agree to not donate sperm for the purposes of reproduction during 
the study and for 90 days after the dose is administered 
6. Has normal vital signs at screening visit at rest, after 10 minutes in the supine position: 
a. Oral temperature < 38℃; no recent hot or cold beverages 
b. Resting heart rate is between 60 and 100 bpm. If a subject is a young, healthy volunteer 
without cardiac disease or symptomatology, heart rate 45 to 59 bpm will be allowed.   
c. BP: systolic ≥ 90 mm Hg and ≤ 140 mm Hg; diastolic ≥ 40 mm Hg and ≤ 90 mm Hg.  
d. Respiratory rate < 20 respirations per minute 
7. Suitable veins for cannulation/multiple venipunctures as assessed by the Investigator or 
designee at screening.  
8. In the opinion of the Investigator, the subject is able and willing to adequately comply 
with all required study procedures and restrictions for the duration of the study. 
8.2. 
Subject Exclusion Criteria 
Subjects must not meet any of the following exclusion criteria to be eligible for participation in 
this study: 
1. Any clinically significant medical conditions or medical history that, in the opinion of the 
Investigator or Sponsor, would interfere with the subject’s ability to participate in the 
study or increase the risk of participation for that subject*.   
*Note: Significant medical history would include, but not be limited to, kidney disease with creatinine 
clearance < 90 mL/min/1.73m2, known active liver disease (including steatosis), ischemic heart disease, 
cardiac conduction disorder, chronic intestinal disease, hypertension (including treated), arrhythmia 
requiring treatment, diabetes requiring insulin, neuropathy, myopathy, and malignancy (not including 
squamous cell skin cancer, basal cell skin cancer, or cervical low-grade squamous intraepithelial lesions).    


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2. Any clinically significant psychiatric condition or history of psychiatric condition that, in 
the opinion of the Investigator or Sponsor, would interfere with the subject’s ability to 
participate in the study or increase the risk of participation for that subject.  
3. Abnormal ECG at the screening visit*.  
*Note: Abnormalities include, but are not limited to, a QTcF > 450 ms in men or > 460 ms in 
women, a PR > 220 ms, or ventricular and/or atrial premature contractions that are more frequent 
than occasional, and/or as couplets or higher in grouping, second or third degree heart block, or 
long QT syndrome. 
4. Clinically significant abnormalities found on the screening echocardiogram*.   
*Note: Abnormalities include but are not limited to: ejection fraction (EF) <55% or structural 
abnormality including valvular and septal defects.  Incident mitral valve prolapse (MVP) with 
none-to-trace regurgitation is not an exclusion. 
5. Known family history of sudden death or long QT syndrome, or family or personal 
history of QT prolongation, or poison/drug induced arrhythmia that required medical 
intervention. 
6. History of or current implanted defibrillator or pacemaker. 
7. Any inclusion laboratory test performed at screening with an abnormal result that is 
DMID Grade 1 or greater. The inclusion tests are defined to be: alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, urine protein, 
hemoglobin, serum potassium, and white blood cell count (Table 6).  
8. Any other screening laboratory test (other than the above stated inclusion tests) with an 
abnormal result that is DMID Grade 2 or higher (Table 6).  
9. Current participation in any other investigational drug study or participation in an 
investigational drug study within 30 days of the Screening visit, or 5.5 half-lives of the 
investigational drug.  Eligible subjects should not have more than 100 mL of blood 
withdrawn in an investigational study in the 30 days prior to participation in this study. 
10. Subject use of any prescription, over-the-counter medications, or herbal supplements* is 
prohibited during the study.  Use of any of the medications specified in Section 9.12 are 
prohibited in the 30 days prior to the study. 
*Note: an exception is the use of any contraceptive medication allowed under the protocol and up to 2 
g/day of acetaminophen for a period of 7 days prior to and during the study.  Over-the-counter medications 
including herbal products not otherwise excluded per Section 9.12 must be stopped 7 days prior to the 
study.   
11. History of drug abuse within the year prior to the screening visit, or current evidence of 
drug dependence.   
Note: A positive result for any drug listed in Table 8 on the drug screen is exclusionary.   
12. Self-reported alcohol intake > 3 drinks/day or a positive alcohol test.  
13. A positive cotinine test.   


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14. Positive serology for human immunodeficiency virus (HIV) or active infection with 
hepatitis B virus (HBV) or hepatitis C virus (HCV).   
15. Pregnant, lactating, or planning to become pregnant during the study or within 30 days of 
dosing. 
16. Donation or loss of > 400 mL of blood within the 3 months prior to screening. 
17. History of severe adverse reaction to or known serious hypersensitivity to any drug.   
18. Presence or history of severe allergic reaction with generalized urticaria, angioedema, or 
anaphylaxis requiring treatment, as judged by the Investigator.   
19. Employment by the study site, or an immediate family relationship to either study site 
employees or Sponsor employees. 
20. Male subjects with pregnant female partners 
Table 6:    Screening and Inclusion Laboratory Tests 
DMID 2014* Grade ≥ 1 value is exclusionary1 
DMID 2014* Grade ≥ 2 value is exclusionary1 
Chemistry 
Hematology 
Chemistry 
Hematology 
Alanine aminotransferase 
(ALT)  
Aspartate aminotransferase 
(AST)  
Bilirubin (total) 
Serum Potassium 
creatinine 
Hemoglobin  
White blood cell count2 
 
Albumin  
Amylase 
Blood glucose 
Blood urea nitrogen (BUN) 
Creatine Phosphokinase 
(CPK) 
Electrolytes (calcium, 
sodium, phosphorus) 
Total serum protein 
Alkaline phosphatase (ALP) 
Eosinophils 
Lymphocytes 
Platelets 
Urinalysis 
Urinalysis 
Coagulation 
Protein on dipstick (1+ or 
higher is exclusionary) 
 
Blood (microscopic) 
 
Prothrombin time (PT) 
Activated partial 
thromboplastin time (aPTT) 
 
1 Laboratory values that are outside the range of eligibility but are thought to be due to an acute condition or due to laboratory 
error may be repeated once. 
2  Subjects who are of African (e.g., African American) or Middle Eastern descent may have a white blood cell count and/or an 
absolute neutrophil count that is in the DMID Grade 1 toxicity range and still be eligible for the study if all other study criteria 
are met.   
*Modified DMID 2014 toxicity table 
8.3. 
Additional Study Restrictions  
Other protocol restrictions that will occur during their confinement in the CRU are listed below: 
• Subjects will abstain from all bergamottin-containing fruits and fruit juices (e.g., 
Seville oranges, grapefruit, grapefruit juice, pomelos, pomegranate or pomegranate 


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juice, cranberry or cranberry juice, caffeine or other xanthine-containing foods and 
beverages from Day -1 until discharge from the CRU on Day 5, 96 hours post dose. 
• Subjects should refrain from eating food containing poppy seeds for 2 days prior to 
Day -1 admission until discharge from the CRU on Day 5, 96 hours post dose.  
• Subjects will abstain from alcohol consumption for 2 days prior to Day -1 admission 
through the follow-up visit on Day 21. 
• Subjects will be asked to avoid strenuous exercise from 7 days prior to Day 1 through 
the last follow-up visit on Day 21.  
Protocol restrictions should be reviewed at screening and Day -1 admission to the CRU. 
8.4. 
Subject Withdrawal Criteria 
8.4.1. 
Withdrawal from Study Drug and Study 
Reasons for study drug withdrawal (ie, halting of the infusion) are described in Section 7.6.3.1.   
Participation in the study is strictly voluntary. Subjects have the right to withdraw from the study 
at any time, including during the infusion, and for any reason. A subject’s participation in the 
study will be terminated only for the following reasons: 
• Subject request to discontinue his or her participation in the study for any reason 
• Subject noncompliance, such as a significant protocol deviation 
• Discontinuation at the request of the Sponsor, regulatory authority, or IRB 
Subjects who withdraw or are withdrawn from the study who received any amount of the study 
product will be encouraged to continue follow-up (with subjects’ consent) for safety.   Subjects 
who withdraw will be asked to complete a final termination visit if they do not wish to be 
followed per protocol. 
8.5. 
Replacement of Subjects 
Replacement subjects may be enrolled as needed for the study to obtain the required number of 
evaluable subjects. An evaluable subject is defined as a subject who has sufficient PK samples 
collected to determine PK parameters through 24 hours post-dose and has sufficient safety data 
(including ECGs, ECHOs, vital signs, PE findings, and clinical lab data) through 24 hours post-
dose to allow for the evaluation of the primary objective.  At least 5 evaluable subjects who 
received galidesivir are required per cohort. Replacement subjects will be allowed if PK 
parameters (through 24 hours post-dose) cannot be determined due to a subject’s early 
discontinuation from the study drug or study.   
Subjects who have an IV infusion stopped for non-drug related issues, as described in 
Section 7.6.3.1, will not continue with dosing but will have all scheduled safety assessments 
made.  These subjects may be replaced as needed. Subjects who have an IV infusion stopped for 
a safety related issued will not continue with dosing and will be followed as per Section 8.4.1. 
These subjects may be replaced if needed to fulfill the required number of evaluable subjects.    


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Subjects who withdraw due to a galidesivir-related AE will not be replaced. Subjects who 
withdraw for other reasons may be replaced at the discretion of the Investigator and Sponsor to 
ensure a sufficient number of evaluable subjects at the end of the clinical study.  
Following the infusion, one subject per cohort may withdraw prior to the completion of Day 5 
without being replaced.  Should more than 1 subject from the same cohort who did not meet the 
above criteria voluntarily withdraw from the study, those subjects may be replaced. 
In the event that a replacement subject withdraws, the subject will not be replaced.   
9. 
TREATMENT OF SUBJECTS 
9.1. 
Treatments Administered 
Subjects will be administered a single dose of study drug or placebo per dose cohort as shown 
below: 
Table 7: 
Dosing per Cohort 
Cohort/ 
Regimen 
Dose 
(mg/kg) 
Calculated Dose 
Rangea 
(mg) 
Galidesivir 
Concentrationb/Placebo 
 
Galidesivir/ 
Placebo Dose 
Volume (mL) 
1/ A 
5 
250-500 
1.0 mg/mL or placebo 
250–500 
2/ B 
10 
500–1000  
1.0–2.0 mg/mL or placebo 
500  
3/ C 
15 
750–1500  
1.5–3.0 mg/mL or placebo 
500  
4/ D 
20 
1000–2000  
2.0–4.0 mg/mL or placebo 
500  
a Based on inclusion criterion No. 4 in Section 8.1, subjects must weigh ≥ 50 kg (110 lb.) and ≤ 100 kg (220 lb.). 
b  Maximum concentration is 4 mg/mL. The lowest concentration of drug used in this study will be 1.0 mg/mL. Rate 
of infusion and volume infused will be adjusted as required for different concentrations, but the total length of the 
infusion will remain 60 minutes. Details on calculating infusion volume will be provided in a separate Pharmacy 
Manual. 
 
Based on PK and safety data emerging from the cohorts, subsequent cohort doses may be 
modified. Modifications to the planned dose escalation schema may be implemented without 
modification of the protocol according to the halting/cohort modification rules described in 
Section 7.6.3. If more than 4 cohorts are required for the SAD, a protocol amendment will be 
implemented to enable enrollment of further cohorts 
9.2. 
Description of Investigational Medicinal Product 
Galidesivir for IV infusion is a sterile, nonpyrogenic solution with a concentration of 100 mg per 
1 mL (100 mg/mL) and a pH adjusted to 3.0. The 100 mg/mL solution may appear clear to 
colorless to brownish. Excipients include Sterile Water for Injection USP/EP, Hydrochloric Acid 
NF/EP or Sodium Hydroxide NF/EP may be used for pH adjustment. Galidesivir for IV infusion 
is supplied by BioCryst in 2 mL single-use amber glass vials fitted with rubber stoppers and 
aluminum flip-off seals. Each 2-mL vial contains a fill volume of 1.2 mL.   


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The study drug, including IV lines will be masked, as described in Section 7.5 in order to 
maintain the study blind.  Additional details can be found in the study-specific Pharmacy 
Manual. 
Stability of diluted concentrations of galidesivir in 250 mL injection bags has been established 
for concentrations between 1 and 15 mg/mL. The IV solution is stored at room temperature 
(15˚C to 25˚C) for up to 24 hours as described in Section 9.5.  The pH of the galidesivir solution 
in LR is between 4.0 and 5.0 (Alcami 2016).   
Additional details for the chemical and physical characteristics of galidesivir may be found in the 
IB. 
9.3. 
Description of Placebo 
LR Solution for Injection, USP will be used as the placebo. The volume for infusion should 
match the volume used in the active treatment in the respective cohort. 
LR solution will be provided by PRA Health Sciences.   
9.4. 
Study Drug Packaging and Labeling 
Study drug will be labeled with the following information: 
• Sponsor name and contact information 
• Study protocol number and name of PI 
• Lot number 
• Description of the contents of the container 
• Route of administration 
• Conditions for storage 
• Statement regarding the investigational (clinical study) use of the drug, which will 
state “Caution: New Drug – Limited by Federal (United States) law to investigational 
use.”  
9.5. 
Study Drug Storage 
Galidesivir vials (100 mg/mL) are stored at 15˚C to 25˚C (59˚F to 77˚F). 
Galidesivir in LR solution is stored at 15˚C to 25˚C (59˚F to 77˚F) for up to 24 hours. 
LR solution (placebo) must be stored as per package insert (room temperature [25˚C]). Avoid 
excessive heat. Protect from freezing. 
Study drug will be reconciled and destroyed (or returned) in accordance with the study 
monitoring plan. 


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9.6. 
Study Drug Preparation 
Study drug preparation will be performed by a research pharmacist on the same day of study 
drug administration and must be prepared in a sterile environment (eg, biological safety cabinet 
or laminar flow hood) using aseptic technique.   
Prior to opening the study drug vial, it should be gently mixed by inverting several times and 
inspected under a bright light to ensure there are no particulates in the vial. Using aseptic 
technique, an appropriately sized sterile needle and syringe must be used to draw the appropriate 
dose and volume of galidesivir or placebo. The syringe must not any individual vial more than 
once. The appropriate dose and volume of galidesivir or placebo will be added to the appropriate 
amount of LR solution in an infusion bag.    
To maintain blinding, once prepared and labeled, the research pharmacist will mask the IV bag 
and tubing (ie, with the use of an overlay or masking tape) to blind the color of the solution in 
the IV bag. In addition, the calculated volume for the placebo must match the corresponding 
calculated volume for the active drug. Additional details can be found in the study-specific 
Pharmacy Manual.  
9.7. 
Administration 
Galidesivir or placebo in LR solution will be administered IV via a peripheral venous catheter 
inserted into the arm of the subject. Study drug will be infused over 60 minutes via 
programmable infusion pump. The maximum rate expected for infusion is 8.33 mL/min. The 
catheter will be maintained and replaced as per institutional policies at the CRU. 
An unblinded dosing team may be utilized in this study if required in order to prevent any 
inadvertent unblinding of study drug while connecting the masked IV bags with the infusion 
pumps (eg, any drips of the dosing solution during connection of the bag to the infusion pump or 
a temporary need to remove part of the masking tape or overlay on the IV tubing to make the 
connection).  Members of the unblinded dosing team will not be involved in any assessments on 
the study and will only be utilized for dose administration.  The unblinded dosing team should 
ensure that the study drug product is blinded to the subject and rest of the study personnel.   
In the event that an infusion must be stopped in the middle of dosing for a subject, the subject 
will not contribute to the PK population, and will be removed from further dosing but will 
continue to be followed for safety assessments per protocol (Section 7.6.3). If the infusion is 
stopped for a non-drug related issue such as pump failure, asymptomatic extravasation, then the 
subject may be replaced as needed.  
A physician must be present at the time of study drug administration and present in the unit for a 
minimum of 4 hours after completion of the infusion.  
9.8. 
Treatment Compliance 
IV infusions of galidesivir or matching placebo in LR solution will be administered by the PI or 
qualified designee licensed to administer study medications. Compliance will be directly 
observed by study staff. Details of doses administered and dosing times will be recorded by 
study staff in the subject’s source documentation/eCRF. Any episodes of incomplete study drug 
administration will be recorded. 


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9.9. 
Study Drug Accountability 
The Investigator must maintain accurate records of the disposition of all study drugs received 
from the Sponsor, and directly administered to the subject on a drug accountability form 
(including date and time). The site PI may delegate to the site research pharmacist the 
responsibility for study product accountability. The site research pharmacist will be responsible 
for maintaining complete records and documentation of product receipt, accountability, 
dispensation, temperature and storage conditions, and final disposition of study product. Each 
investigational product will have a separate drug accountability form. At the end of the study, 
information describing study drug supplies (eg, lot numbers) and disposition of supplies must be 
provided, signed by the Investigator or designee, and collected by the study monitor.  
9.10. 
Study Drug Handling and Disposal 
At the end of the study, all medication that was not administered and used packaging materials 
will be returned to the Sponsor or destroyed on site as instructed by the Sponsor following IMP 
accountability by the study monitor and abiding by appropriate Standard Operating Procedure at 
the participating institution. 
9.11. 
Concomitant Medications 
Any medications used will be recorded in the source document and eCRF.  
Emergency equipment and drugs will be available within the CRU as per current standard 
procedures. In the unlikely event that they are required, their use will be documented. 
9.12. 
Prohibited Medications 
Use of the following medications is prohibited 30 days prior to dosing through the Day 21 
follow-up visit: 
• Medications that are clinically known to induce or inhibit metabolic enzymes or 
transporters according to the FDA Drug Interaction Guidance (DHHS 2017).   
− A list of metabolic and transporter inducers and inhibitors can be found at: 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResource
s/DrugInteractionsLabeling/ucm093664.htm  
• Medications that are clinically known or suspected to prolong the QT interval 
− Medications falling into the category of drugs with a risk of torsades de pointes 
and drugs with a possible risk of torsades de pointes are listed at:  
https://crediblemeds.org/ 
Both lists will be provided to the study site by the Sponsor. 
In addition, use of investigational agents is prohibited within 90 days of screening through the 
follow-up visit. 


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9.13. 
Food and Drink 
Following check-in procedures on Day -1, subjects will be provided with appropriate meals and 
will fast from all food for approximately 8 hours overnight prior to the morning of Day 1, when 
subjects will receive a standardized light breakfast 1 hour prior to dosing (standardized means 
the same breakfast will be administered to all subjects in all cohorts). Water or another beverage 
will be allowed during the meal prior to dosing.  Approximately 4 hours after dosing, a 
standardized lunch will be served. Dinner should be served approximately 9 hours after the start 
of dosing. Meals and snacks following dinner on Day 1 may be administered per routine clinic 
practice.  
Water will be provided ad libitum up to 2 hours prior to and 2 hours post the start of dosing. 
10. 
STUDY CONDUCT 
10.1. 
Schedule of Assessments 
The schedule of assessments in this study is summarized in Table 5 and described in more detail 
in Section 11.   
Screening procedures are presented in Section 10.1.1.  Study procedures are presented in Section 
Section 10.1.2 .  Follow-up procedures conducted on Day 21 will be the same as any early 
termination visit procedures and are presented together in Section 10.1.3. 
10.1.1. 
Screening 
Prospective subjects should be screened within 28 days prior to Day 1. Written informed consent 
must be obtained from each subject before initiation of any screening assessments or procedures. 
Each subject will receive a copy of the signed and dated study-specific Informed Consent Form 
(ICF). Prospective subjects who have signed an ICF and who are interested in participation in the 
study will then undergo assessments at a screening visit to determine eligibility.  
The Investigator (or designee) will conduct the following assessments at the screening visit: 
• Review inclusion and exclusion criteria for study eligibility 
• Collect demographic data  
• Review medical and medication history  
• Height, weight, and BMI  
• Drug screen, urine alcohol and urine cotinine test 
• Blood collection for screening labs (see Table 6 for list of labs), HBV/HIV/HCV 
serology, FSH (for women who declare that they have been post-menopausal ≤ 2 years) 
• Serum pregnancy test for all women  
• Urinalysis  
• Determine urine albumin to creatinine ratio (UACR) 
• Vital signs (heart rate, BP, temperature) 


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• Physical examination including vein assessment 
• 12-lead ECG 
• ECHO (Note: ECHO may be performed at any time from screening to Day-2.  The 
ECHO should be done after a subject is otherwise deemed eligible for the study.  The 
ECHO is required to determine eligibility, so it must be conducted prior to Day -1 CRU 
check-in).   
For height and weight measurements, subjects will be allowed to wear indoor clothing, without 
shoes.  
Demographic data will include date of birth, sex, race and ethnicity. 
All screening data must be obtained within 28 days prior to administration of study medication, 
as stipulated above. 
Rescreening of ineligible subjects, where there is a reasonable expectation that the subject will 
become eligible, will be approved or denied on a case-by-case basis by the Investigator. In the 
case of rescreening, the Investigator may request all or a subset of the required assessments to be 
redone. Subjects may only be rescreened once and all assessments must be performed/drawn 
within the required screening window.  If a subject is rescreened, the subject must be re-
consented.   
If a subject has completed all assessments for screening including the ECHO, but are not dosed 
as part of the cohort (ie, they are a backup subject), the subject may be eligible for a subsequent 
cohort.  For any subsequent cohort that the subject screens for, the subject must complete all 
screening assessments within the appropriate 28-day window, with the exception of the ECHO, 
which does not need to be repeated.  The ECHO from the original screening may be utilized for 
eligibility purposes.  However if a subject failed screening based on the ECHO, they are not 
eligible to repeat screening in a later cohort in the hopes they will have a suitable ECHO.   
10.1.2. 
Study Procedures 
Subjects will check into the clinic on Day -1 and will remain in the clinic until discharge on 
Day 5, 96 hours post dose. Subjects will return to the clinic for brief (1 to 2 h duration) visits for 
PK sampling on Day 6, 8 and 14 and for a final follow-up visit on Day 21.   
Subject identity will be confirmed at check-in.   
Upon check-in on Day-1, subjects will have the following procedures conducted as outlined in 
Table 5: 
• Review of inclusion and exclusion criteria and prohibited medications 
• Medical and medication history   
• Weight 
• Drug screen, urine alcohol and urine cotinine test 
• Urine pregnancy test for all women  
• Safety laboratory assessments (clinical chemistry, aPTT/PT, hematology, coagulation) 


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• Blood drawn for testosterone, troponin I, CK-MB, NGAL, Cystatin C 
• Urinalysis 
• Determine UACR 
• Vital signs (blood pressure and heart rate)  
• Physical examination 
• Review of AEs and concomitant medications 
Note: Testosterone, troponin I, CK-MB, NGAL, Cystatin C samples can be collected on Day-1 
or Day 1 prior to dosing; results are not required prior to dosing. 
On Day 1, the following procedures will be performed as outlined in Table 5 prior to 
administration of galidesivir: 
• Pre-dose urine and blood samples collected for analysis of galidesivir in urine and plasma 
• 12-lead ECG pre-dose in triplicate  
• Cardiac telemetry will be initiated at least 2 hours prior to infusion with telemetry data 
collected for 24 hours post dose  
• Vital signs (BP, and heart rate)  
• Physical examination 
• Review of AEs and concomitant medications  
Galidesivir or placebo infusion is administered over one hour with the following procedures 
performed: 
• Blood samples collected for analysis of galidesivir concentrations at the timepoints 
described in Section 11.2.1 
• Urine samples collected for analysis of galidesivir concentrations at the intervals 
described in Section 11.2.2 
• Daily safety laboratory assessments (clinical chemistry and hematology) 
• 12-lead ECG post dose at specified timepoints noted in Section Section 11.3.1.4 
• Vital Signs (BP, oral temperature, and heart rate)  
• Physical examination  
• Review of AEs and concomitant medications  
Subjects will be discharged on Day 5 96 hours post dose after all assessments and procedures are 
completed as denoted in Table 5. 
Subjects will be asked to return to the clinic for brief visits for collection of PK samples on 
Days 6 (+1), 8(+1), and 14 (±1). The following procedures will be performed at those visits: 
• Blood sample collected for analysis of galidesivir concentrations  


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• Review of AEs and concomitant medications. If any reported AEs require additional 
assessments (PE, vital signs, laboratory tests), the required assessments to evaluate the 
AE should be completed at these visits.  
10.1.3. 
Follow-up/Early Termination Visit 
Subjects will return to the clinic on Day 21 +2 for a follow-up visit.  If a subject terminates from 
the study at any point prior to the scheduled follow-up visit, the assessments listed below should 
be performed at that time.   
The following procedures will be performed at the follow-up visit: 
• Safety laboratory assessments (clinical chemistry, aPTT/PT, hematology, coagulation) 
• Blood drawn for testosterone, troponin I, CK-MB, NGAL, Cystatin C 
• Urinalysis 
• Determine UACR 
• 12-lead ECG  
• Vital Signs (blood pressure and heart rate)  
• Physical examination 
• Review of AEs and concomitant medications 
• Blood sample collected for analysis of galidesivir concentrations  
• Urine pregnancy test for all women  
11. 
ASSESSMENTS 
11.1. 
Investigator-Completed Assessments 
Demographic information, including year of birth, sex, race or ethnicity, and medical and 
medication history will be captured for each subject participating in the study at the Screening 
visit. Medical history, medication review, and review of inclusion and exclusion criteria and 
prohibited medications will also be rechecked as outlined in Table 5.  
There are times where the protocol requires more than one procedure to be completed at the 
same time point. In these instances, the following will apply to post dose time points:  
• PK samples will take precedence over other procedures and will therefore be collected at 
the nominal time. An exception to this is the collection of chemistry lab samples which 
should be collected in the order listed in Section 11.3.1.7. 
• Vital signs will be recorded after the nominal time 
• ECG recordings will be taken prior to the nominal time (prior to the PK sample) 
The Investigator, or a qualified designee, should complete the assessments listed in the protocol. 


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11.2. 
Pharmacokinetic Assessments 
11.2.1. 
Blood Sample Collection 
Twenty-three blood samples for the measurement of plasma concentrations of galidesivir will be 
collected at the following time points:  
• Pre-dose, halfway through the infusion (30 minutes), 1 hour (end of the infusion) 1.25, 
1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, and 96 hours post dose. 
• Day 6 (+1 day), Day 8 (+1 day), Day 14 (± 1 day) 
• Day 21 (+ 2 days) or early termination 
Subjects will have a cannula placed for administration of the infusion in one arm, and blood 
samples for PK will be collected from the other arm, either through direct venipuncture or an 
indwelling cannula. All cannulas placed will be maintained according to the policies of the unit 
while in use.  All samples are timed from the start of the infusion. 
The PK sample collection time points may be modified based on the concentration-time course 
found in the early cohorts. For subjects randomized to placebo, only the 5-minute post-infusion 
sample will be analyzed. The pre-dose PK sample must be collected within ≤ 1 hour of the dose. 
Within the first 2 hours post-dose, an acceptable window around each PK draw is ± 2 minutes. 
After 2 hours, an acceptable window is ± 10 minutes while the subject is in the unit. For the 
samples collected when the subjects return to the CRU post-discharge, the appropriate window is 
as noted above. 
11.2.2. 
Urine Sample Collection 
For the analysis of galidesivir, an aliquot of urine will be collected pre-dose (0 hour) and all 
urine will be collected for the following post-dose intervals: 0–12, 12–24, 24–48, 48–72, and 72–
96 hours. A window of ± 30 minutes at the end of each interval is acceptable. For timing of the 
intervals, time 0 starts at the time of dosing.  For the pre-dose sample collection, the urine sample 
should be collected within 2 hours prior to dosing.   
The total volume of all urine collected during each time interval will be recorded in the source 
documentation/eCRF. For subjects who are randomized to placebo, no urine will be analyzed for 
galidesivir concentrations. 
11.2.3. 
Sample Analysis 
All plasma and urine determination of galidesivir will be analyzed using a validated liquid 
chromatography-tandem mass spectroscopy assay. Instructions for collection, processing, 
storage, and shipment of PK samples will be provided to the clinical site in a separate Clinical 
Sample Processing Manual. 


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11.3. 
Assessment of Safety 
11.3.1. 
Safety Parameters 
11.3.1.1. Vital Signs 
Vital signs include measurements of heart rate, BP, and temperature. BP (systolic and diastolic), 
pulse rate, and temperature should be taken after the subject has rested in the supine position for 
at least 10 minutes. Respiratory rate is a required vital sign at Screening for eligibility and should 
be taken after the subject has rested in the supine position for at least 10 minutes.  BP 
measurements must be obtained with an appropriate cuff size and with the subject’s arm 
supported at the level of the heart. It is acceptable to obtain a pulse rate from the BP or ECG 
machine. Grade 2 or higher vitals will be repeated in 30 minutes if abnormal. 
Pre-dose vital signs must be collected within 2 hours of the IV infusion. Post dose vital signs 
may be obtained within 10 minutes of the nominal time point. Any abnormality should be graded 
on a scale from 0 (none) to 3 (severe) using the modified 2014 DMID Adult Toxicity Grading 
Scale; APPENDIX A) and reported as an AE if appropriate as per Section 11.4.1.1. If the event 
is more severe than a Grade 3, severity criteria as described in Section 11.4.1.2 should be used to 
characterize the event. 
11.3.1.2. Weight/Height/Body Mass Index 
For determination of height and weight, subjects should be dressed, without shoes. BMI should 
be calculated using the following formula: 
 
BMI = weight (kg)/height (m)2 
Weight/BMI will be collected at screening for eligibility determination. Weight will be collected 
on Day -1 in order to complete the dosing calculations.   
11.3.1.3. Physical Examination 
A PE consisting of the head and neck, skin, chest (lungs and heart), abdomen (gastrointestinal 
tract, liver, spleen and kidneys), back, musculo-skeletal system, neurologic system should be 
conducted at screening and at discharge from the unit. Breast and genitourinary system do not 
require examination unless the potential subject indicates a complaint or comorbidity that could 
result in exclusion. 
All subsequent PEs may be symptom driven based on the subject’s interim medical history. 
11.3.1.4. 12-Lead Electrocardiogram  
A standard bedside 12-lead ECG machine that calculates heart rate and measures the PR, QRS, 
QT, RR, and QTc (QTcF) intervals will be utilized. Prior to obtaining an ECG, subjects must rest 
quietly in a supine position for at least 10 minutes. 
Qualified site personnel should review the ECGs and automated findings from the Day 1 pre-
dose and post dose ECGs prior to the next day’s dosing or scheduled assessments for gross 
abnormalities and interval measurements of concern (absolute readings and for post dose ECGs, 


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change from baseline). For all ECGs, the clinical interpretation of the ECG should be recorded 
directly on a hard copy of the ECGs. Copies of the ECGs may be requested by the Sponsor. 
Screening and baseline (Day 1 pre-dose) ECGs will be obtained in triplicate at 1- to 5-minute 
intervals, with baseline values calculated from an average of the three readings. The pre-dose 
ECG should be collected within ≤ 2 hours of the first dose. Thereafter, single assessment ECG 
will be performed on Day 1 at 2 and 4 hours post dose, Day 2 at 24 hours post-dose and on Days 
3 and 4 while the subject is in the CRU. An acceptable window is ± 10 minutes from the nominal 
time point while the subject is in the CRU. An ECG will also be performed at the Day 21 follow-
up visit.  All ECGs should be obtained per the schedule of assessments in Table 5.  
An ECG should be repeated for a change from baseline in QTcF > 30 ms. 
An ECG will also be performed if a Grade 3 electrolyte abnormality (such as hyperkalemia) is 
detected to determine if there are any ECG-related changes and/or arrhythmias.  ECGs will also 
be performed if a subject reports any AE symptoms that are indicative of cardiac signs or 
symptoms. 
11.3.1.5. Cardiac Telemetry 
Standard cardiac telemetric monitoring will begin ≥ 2 hours prior to dosing. Telemetry will 
continue for 24 hours post-dose. Subjects may be disconnected from telemetry for 10-minute 
intervals every 2 hours while awake during which time they may engage in mild physical activity 
such as walking or calf exercises. In addition, they may be disconnected for bathroom visits and 
personal hygiene needs, as well as for three 20-minute periods for meals. 
Telemetry will be monitored in real time by qualified personnel, with the assistance of alarms.  If 
no abnormal rhythms are detected during the observation period, this will be recorded in the 
source documents along with the exact start and stop times of telemetric observation. 
The telemetry monitors will be programmed to automatically create a printed tracing of any 
arrhythmia, including tachycardia of Grade 2 or higher (i.e., heart rate greater than 115 bpm). A 
rhythms tracing can also be manually printed if the staff notes a rhythm that requires evaluation 
but did not automatically print. The occurrence of an arrhythmia or tachycardia will trigger the 
evaluation of the subject. If the tracing is found to be due to artifact (ie, subject motion), the 
tracing will be noted to be ‘not clinically significant’ and will be documented in the source 
documents. The monitor will be programmed to alarm when an abnormal tracing is obtained. 
Any abnormality that is found to be clinically relevant will be documented in the source 
documents, recorded as an AE, graded per the modified 2014 DMID toxicity scale 
(APPENDIX A) and potentially trigger additional evaluations as deemed medically appropriate 
(eg, an ECG, pharmacologic treatment) by the PI. 
11.3.1.6. Echocardiogram 
ECHOs will be obtained per the schedule of assessments (Table 5). The ECHO may be 
performed at any time from screening to Day -2 for eligibility determination. An ECHO will also 
be performed on Day 4. An acceptable window for the Day 4 ECHO is up until Day 5 discharge.  
The ECHO will be performed by trained cardiac sonographers who will provide a real-time 
assessment of EF and cardiac structure. Subjects must have an EF ≥ 55% and have no structural 
abnormalities other than incidental MVP with none-to-trace regurgitation. The screening and 


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subsequent ECHO images will be maintained until the subject has completed the study. 
Subsequent ECHOs will be performed in a similar manner by a trained sonographer. All ECHOs 
will be read by a cardiologist. Pre-dose ECHOs will be read prior to dosing. Any new 
abnormalities identified on post-baseline ECHOs confirmed by the cardiologist will be 
documented as AEs and graded as per severity grading scale provided in Section 11.4.1.1. 
11.3.1.7. Clinical Laboratory Screening and Safety Assessments 
Blood and urine samples will be obtained per the schedule of assessments (Table 5). Screening 
inclusion laboratory tests are listed on Table 6. A list of all laboratory tests that will be 
performed during the study are provided in Table 8.  Laboratory assessments do not require 
fasting conditions. Acceptable windows for collection of blood samples for laboratory 
assessments are the same as for the PK samples. Urinalysis (post dose) has an acceptable 
window of ± 2 hours from the nominal time as designated in Table 5. Samples will be collected 
into appropriate tubes as specified by the clinical laboratory.  
Study eligibility is partially determined by screening laboratory tests. Inclusion laboratory test 
results must be within acceptable eligibility range for all labs listed in Table 6 at Screening. For 
all clinical laboratory safety assessments, the laboratory results values obtained on Day -1 
establish the baseline for chemistry, hematology, and coagulation laboratory safety results. 
Results for Cystatin C, NGAL, and free testosterone (males only) do not need to be obtained 
prior to initiation of dosing.  These tests will be used for baseline measurements for post-dose 
comparison for evaluation of renal and testicular health following administration of galidesivir. 
At time points when multiple samples are taken, the samples will be taken in the following order 
to minimize the risk of K EDTA contamination of the biochemistry samples. 
1. Coagulation 
2. Biochemistry / testosterone 
3. PK 
4. Hematology 
Laboratory values drawn after study drug dosing should be assessed within 12 hours of receipt 
by the PI or qualified designee. Safety laboratory assessments can be taken anytime post-dose on 
Days 1 to 5 to fit with the clinic and lab schedule.  Results from safety laboratory assessments 
are not required for completing assessments on the following day.  Any laboratory findings 
outside of the normal range should be documented and described in the source documentation. 
Results from baseline and on-treatment clinical chemistry, hematology, coagulation, and 
urinalysis tests will be provided to the Sponsor for real-time review.   
Laboratory abnormalities outside of the normal laboratory reference ranges and associated 
grades (according to study specific DMID criteria (modified 2014 DMID Adult Toxicity Grading 
Scale) see APPENDIX A) should be denoted where possible. For those analyte results that are 
out of the normal range and do not have an established DMID toxicity criteria, the PI should 
assess the abnormalities and provide severity grading as defined in Section 11.4.1.2.  
All laboratory samples will be analyzed by a local laboratory associated with the site. Reference 
ranges for each local laboratory will be provided to the Sponsor and included in data listings. For 


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out-of-range laboratory findings, the interpretation of clinically significant or not clinically 
significant should be denoted in the source records. Clinically significant laboratory findings in 
the opinion of the Investigator should be recorded as AEs and handled as described in 
Section 11.4.  Laboratory abnormalities that are not deemed to be clinically significant by the 
Investigator are not reported as AEs.  All laboratory findings will be summarized and reported 
with appropriate grading, regardless of whether or not they are reported as AEs.   
Cystatin C, NGAL, testosterone, CK-MB, troponin and UACR will be analyzed as outlined in 
the Statistical Analysis Plan.  Briefly, changes from baseline will be measured for each analyte.  
Values outside the normal limits, if applicable, will be graded based on fold changes in 
comparison to the upper or lower limit of normal.  Marked changes in these analytes will be 
taken as potential indications of impaired organ function and qualitative interpretation will take 
into account subject incidence, clinical course, and comparison to placebo for the safety analyses 
in the final study report. 
 
 


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Table 8: 
Clinical Safety Laboratory Evaluations 
Chemistry 
Hematology 
Albumin 
Alkaline phosphatase (ALP) # 
Alanine aminotransferase (ALT) # 
Aspartate aminotransferase (AST) # 
Bilirubin (total and direct) # 
Blood glucose  
Blood urea nitrogen (BUN) 
Electrolytes (calcium, sodium, potassium, chloride*, 
phosporous) 
Creatine Phosphokinase 
Creatinine and calculated creatinine clearance# 
Total serum protein 
Amylase with reflex lipase 
Hemoglobin# 
Hematocrit* 
Erythrocytes* 
White blood cell count#,  
White blood cell count differential (lymphocytes, 
monocytes*, neutrophils, eosinophils, and basophils*) 
Platelets 
Urinalysis 
Additional Laboratory Tests 
Bilirubin* 
Glucose  
Leukocytes* 
Ketones* 
Nitrites* 
pH* 
Protein# 
Urobilinogen* 
Presence of blood  
microscopy if dipstick is abnormal (at the discretion of the 
PI) 
Prothrombin time (PT)/international normalized ratio (INR) 
Activated partial thromboplastin time (aPTT) 
Hepatitis B surface antigen, hepatitis C antibody, HIV type 
1*# 
Total Testosterone (male subjects only)*  
Free Testosterone (male subjects only)*  
Troponin I* 
CK-MB 
Cystatin C* 
Urine Albumin-to-Creatinine ratio (UACR)* 
Neutrophil gelatinase-associate lipocalin (NGAL)* 
*Analytes without established DMID toxicity criteria 
 #Analytes that are used for screening laboratory tests per Sections 8.1 and 8.2 
11.3.1.7.1. Virus Serology 
Serology tests for hepatitis B surface antigen, hepatitis C antibody and HIV type 1 will be 
conducted at Screening. Positive serology results are exclusionary; if subjects have a positive 
result, they will be informed in private and told about counseling, and positive lab results will be 
reported per state law.   
 
 


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11.3.1.7.2. Urine Drug Screen and Cotinine Test 
A urine drug screen will be conducted at Screening and Day -1. A positive result for a drug of 
abuse is exclusionary.  Tests for the following drugs will be included in the drug screen: 
• Amphetamines 
• Barbiturates 
• Benzodiazepines  
• Methamphetamine 
• Ecstasy 
• Phencyclidine 
• Tricyclic antidepressants 
• Opiates 
 
Urine alcohol and cotinine tests will also be conducted at Screening and Day -1.  A positive 
result for either test is also exclusionary.  
11.3.1.7.3. Pregnancy Screen 
A serum pregnancy test should be drawn at Screening for all female subjects, regardless of their 
contraceptive status or whether they practice abstinence. FSH will be measured at screening in 
women who declare themselves as postmenopausal for ≤ 2 years to establish childbearing status. 
All other pregnancy tests performed during the study may be urine pregnancy tests. A serum 
pregnancy test should immediately be drawn and sent for analysis following any positive urine 
pregnancy test. 
11.4. 
Adverse Events and Serious Adverse Events 
AEs will be assessed and recorded from the time of signing the ICF through the appropriate 
follow-up period. 
11.4.1. 
Definition of Adverse Events 
11.4.1.1. Adverse Event 
An AE is any untoward medical occurrence in a clinical study subject. No causal relationship 
with the study drug/IMP or with the clinical study itself is implied. An AE may be an 
unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during 
the clinical study. Clinically relevant abnormal results of diagnostic procedures including 
abnormal laboratory findings (eg, requiring unscheduled diagnostic procedures or treatment 
measures, or resulting in withdrawal from the study) are considered to be AEs. Abnormal 
laboratory findings that are not deemed clinically significant by the Investigator are not 
considered to be AEs. 
This includes the following:  
• AEs not previously observed in the subject that emerge during the protocol-specified 
AE reporting period (see Section 11.4).  


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• Findings from protocol-mandated interventions. This can include laboratory 
assessments performed during the clinical study. AEs should only be reported if the 
abnormalities are changes from baseline and are clinically significant as described 
above.  
• Pre-existing medical conditions judged by the Investigator to have worsened in 
severity or frequency or changed in character during the protocol-specified AE 
reporting period.  
An adverse reaction is defined in Article 2(n) of Directive 2001/20/EC as follows: all untoward 
and unintended responses to a study drug/IMP related to any dose administered. The definition 
also covers medication errors and uses outside what is foreseen in the protocol, including misuse 
and abuse of the product. The definition implies a reasonable possibility of a causal relationship 
between the event and the study drug/IMP. This means that there are facts (evidence) or 
arguments to suggest a causal relationship.  
Surgical procedures should not be reported as AEs. The condition for which the surgery is 
required should be reported as the AE, if it occurs or is detected during the study period. Planned 
surgical measures permitted by the clinical study protocol and the conditions(s) leading to these 
measures are not AEs, if the condition(s) was (were) known before the start of study treatment. 
In the latter case the condition should be reported as medical history.  
AEs are designated as “nonserious” or “serious.” 
11.4.1.2. Serious Adverse Event  
An SAE is an AE occurring during any study phase (ie, baseline, treatment, washout, or follow-
up), and at any dose of the investigational product, comparator or placebo, that fulfils one or 
more of the following: 
• Results in death 
• It is immediately life-threatening 
• It requires inpatient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity or substantial disruption 
of the ability to conduct normal life functions 
• Results in a congenital abnormality or birth defect 
• It is an important medical event that may jeopardize the subject or may require 
medical intervention to prevent one of the outcomes listed above. 
Important medical events that may not result in death, are not life-threatening, or do not require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the subject’s health or may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such events may include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, 
or convulsions that do not result in subject hospitalization.  
In addition, the Sponsor considers any abortions (elective or spontaneous), fetal demise, and still 
birth to be SAEs for reporting purposes.  


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Overdose will be considered an SAE only if any of the seriousness criteria are met. Any clinical 
complication in association with the overdose should be reported as an AE or SAE (as 
applicable) along with the event of overdose. Details of signs or symptoms, clinical management, 
and outcome should be reported, if available. Overdose without associated signs or symptoms 
should not be recorded as AEs but should be recorded as a protocol deviation.  
Severity of Event: All AEs will be assessed (graded) for severity using the modified 2014 
DMID Adult Toxicity Grading Scale (see APPENDIX A). Any AEs not covered by the DMID 
criteria will be assessed and classified into one of three clearly defined severity categories as 
follows: 
Mild: 
(Grade 1): Transient or mild symptoms; no limitation in activity; no 
intervention required. The AE does not interfere with the participant’s normal 
functioning level. It may be an annoyance. 
Moderate: 
(Grade 2): Symptom results in mild to moderate limitation in activity; no or 
minimal intervention required. The AE produces some impairment of 
functioning, but it is not hazardous to health. It is uncomfortable or an 
embarrassment. 
Severe: 
(Grade 3): Symptom results in significant limitation in activity; medical 
intervention may be required. The AE produces significant impairment of 
functioning or incapacitation. 
Severity refers to the medical perspective of an event whereas seriousness reflects the outcome 
of the event (ie, hospitalization). Events of mild severity can lead to hospitalization and therefore 
be serious whereas severe events such as a headache may not meet seriousness criteria.  
Changes in the severity of an AE should be documented to allow an assessment of the duration 
of the event at each level of intensity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
11.4.1.3. Adverse Events of Special Interest  
No adverse events of special interest have been identified for galidesivir.   


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11.4.2. 
Relationship to Study Drug 
The PI or medically qualified designee must review each AE and make the determination of 
relationship to study drug using the following guidelines.  The Sponsor uses five categories of 
relatedness. The category of “Not Related” and “Likely Not Related” map to the DMID category 
of “Not Related”, whereas the categories of “Possibly Related”, “Probably Related” and 
“Definitely Related” map to the DMID category of “Related”. The categories are described 
below: 
Not Related: 
The event can be readily explained by other factors such as the subject’s 
underlying medical condition, concomitant therapy, or accident, and no 
temporal relationship exists between the study drug and the event. 
Likely Not 
Related: 
The event does not follow a reasonable temporal sequence from drug 
administration and is readily explained by the subject’s clinical state or by 
other modes of therapy administered to the subject. 
Possibly 
Related: 
There is some temporal relationship between the event and the administration 
of the study drug and the event is unlikely to be explained by the subject’s 
medical condition, other therapies, or accident. 
Probably 
Related: 
The event follows a reasonable temporal sequence from drug administration, 
abates upon discontinuation of the drug, and cannot be reasonably explained 
by the known characteristics of the subject’s clinical state. 
Definitely 
Related: 
The event follows a reasonable temporal sequence from study drug 
administration, follows a known or suspected response pattern to the study 
drug, is confirmed by improvement upon stopping the study drug 
(dechallenge), and reappears upon repeated exposure (rechallenge, if 
rechallenge is medically appropriate). 
The clinician’s assessment of an AE's relationship to study drug is part of the documentation 
process. All AEs whether or not deemed related to study drug require reporting. If there is any 
doubt as to whether a clinical observation is an AE, the event should be reported 
11.4.3. 
Recording Adverse Events 
AEs and SAEs will be assessed and recorded from the time of signing of the ICF through the 
appropriate follow-up period. AEs and SAEs will be followed to adequate resolution or 
stabilization to new baseline. 
11.4.4. 
Reporting Adverse Events 
Any SAE must be reported by phone in real time to the Sponsor Medical Monitor and in writing 
using the SAE report form within 24 hours of the PI’s awareness of the SAE via email or fax (or 
both). In addition, all SAEs must be recorded on the AE eCRF in real time. All additional 
follow-up evaluations of the SAE must be reported to BioCryst or its designee as soon as they 
are available. The SAE report forms should be sent to the following email or fax number (or 
both): 


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Email: mmgalidesivir@biocryst.com AND safety@biocryst.com 
Fax: +1 919 226-5888 
Immediate reporting should allow BioCryst to take the appropriate measures to address potential 
new risks in a clinical study. Therefore, the initial report should be submitted by the PI within a 
very short period of time and under no circumstances should this period exceed 24 hours 
following awareness of the SAE. 
The follow-up report should allow BioCryst to determine whether the SAE requires a 
reassessment of the unreasonable risk profile of the study drug in clinical study, if the relevant 
information was not already available and provided in the initial report. 
BioCryst will in turn do the following in real time: 
Contact the DMID medical monitor 
Submit the SAE to: 
DMID Pharmacovigilance Group (PVG), Clinical Research Operations and Management 
Support (CROMS), 6500 Rock Spring Dr. Suite 650, Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (U.S.) or 1-301-897-1709 (outside U.S.) 
SAE FAX Phone Number: 1-800-275-7619 (U.S.) or 1-301-897-1710 (outside U.S.) 
SAE Email Address: PVG@dmidcroms.com 
The DMID Clinical Project Manager and DMID Medical Monitor will be notified of the SAE by 
the DMID PVG. The DMID Medical Monitor will review and assess the SAE for potential 
impact on study subject safety and protocol conduct. 
The Independent Safety Monitor (ISM) will be contacted by the PI in real time, and will then 
assess the event and the subject (see Section 11.5.1). 
The Sponsor is responsible for determining regulatory reporting requirements and will provide 
the PI with reports of suspected unexpected serious adverse reactions (SUSARs). The CRU is 
responsible for submitting any SUSAR or Investigational New Drug (IND) safety report (initial 
and follow-up) or other safety information (eg, revised IB) to the IRB and for retaining a copy in 
its files, unless otherwise instructed. 
11.4.5. 
Regulatory Reporting 
A SUSAR is an unexpected serious AE of which the nature or severity is not consistent with the 
applicable product information (eg, IB) and there is a reasonable possibility that the event was 
due to use of the study drug or due to a protocol-mandated procedure. 
The term “severity” describes the intensity of a specific event and therefore, has to be 
distinguished from the term “serious”. Reports that add significant information about the 
specificity, increase of occurrence, or severity of a known, already documented serious adverse 
reaction constitute unexpected events. 
The expectedness of an adverse reaction is determined by the Sponsor in the Reference Safety 
Information (RSI) on the basis of the events previously observed, not on the basis of what might 
be anticipated from the pharmacological properties of the study drug/IMP. The RSI is contained 


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in the IB in a clearly identified section that includes information on the frequency and nature of 
the adverse reactions. The RSI may change during the conduct of the clinical study and this 
would be a substantial amendment. For the purpose of SUSAR reporting, the version of the RSI 
at the moment of occurrence of the SUSAR applies. 
It is the responsibility of the Sponsor to determine whether an event requires expedited reporting 
and to notify the PI of its decision as soon as possible. SUSARs will be subject to expedited 
reporting. 
Where expedited reporting is required, the following procedures should be followed. 
Fatal or life-threatening SUSARs: 
It is the responsibility of the Sponsor to report fatal or life-threatening SUSARs to the FDA, as 
soon as possible, but no later than 7 calendar days after the Sponsor first became aware of the 
reaction. 
The PI is required to notify the IRB of any SUSAR as soon as possible, but no later than 7 
calendar days after he or she first became aware of the reaction. Any additional relevant 
information should be sent within 8 days of the report. 
Other SUSARs 
It is the responsibility of the Sponsor to report other SUSARs to the FDA as soon as possible, but 
no later than 15 calendar days after it first became aware of the reaction. 
The PI is required to notify the IRB of any other SUSAR as soon as possible, but no later than 15 
calendar days after he or she first became aware of the reaction. 
11.4.6. 
Periodic Reporting 
On an annual basis and as per all local requirements, the Sponsor will provide periodic reports to 
all competent authorities regarding safety for the product. In the United States, this requirement 
is met by submitting an IND annual report or a development safety update report (DSUR) to the 
FDA which will list a summary of most frequent and most serious adverse experiences by body 
system, a summary of all IND safety reports submitted during the reporting period, a list of 
subjects who died during participation and cause of death, and a list of subjects who dropped out 
during the course of the investigation in association with any adverse experience, whether or not 
thought to be drug related.  
11.4.7. 
Reporting of Pregnancy 
Subjects will be instructed that if they/their partner become pregnant during the study this should 
be reported to the PI immediately. The PI should also be notified of pregnancy occurring after 
completion of the study for female subjects 30 days after the last dose of study drug and partners 
of male subjects 90 days after the last dose of study drug. In the event that a subject or subject’s 
partner is subsequently found to be pregnant after the volunteer is included in the study, then 
consent will be sought from the pregnant female subject or partner of a male subject and, if 
granted, any pregnancy will be followed and the status of mother and/or child will be reported to 
the Sponsor after delivery. Any subject who reports pregnancy during the study will be 
withdrawn from the study. 


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While pregnancy is not considered an AE, all cases of fetal drug exposure via the parent as a 
study participant (including partners of study participants) are to be reported immediately to 
BioCryst or its designee. Information related to the pregnancy must be given on a “Pregnancy 
Confirmation and Outcome” form that will be provided by the Sponsor or its designee so that the 
pregnancy may be followed and an outcome determined. Any AEs or SAEs experienced by a 
pregnant subject are to be reported as directed above in Sections 11.4.1.1 and 11.4.1.2. Any 
complications reported in a subject’s pregnant partner should be reported on the Pregnancy 
Confirmation and Outcome form. All pregnancies must be followed to outcome which occurs 
when an infant is delivered (live or still born), when there is fetal demise, or when there is an 
abortion (spontaneous or induced). Any congenital abnormalities in the newborn should be 
reported as separate SAEs. In addition, abortion (spontaneous or elective), fetal demise and 
stillbirth are considered SAEs.  
A pregnancy that is reported while a subject is on study drug through the visit follow-up time 
frame will be captured in electronic data capture (EDC) and reported on the Pregnancy Report 
form for entry into both the clinical database and the safety database. All further follow-up of the 
pregnancy through resolution (abortion, either elective or spontaneous, fetal demise, still birth, or 
live birth) will be captured on a Pregnancy Confirmation and Outcome form and entered only 
into the safety database because these data are not statistically analyzed and would cause the 
clinical database to remain open, thus preventing adequate analysis of the Phase 1 data. 
Pregnancy in a subject that is reported after the final study visit until 30 days after the last study 
drug dose for female subjects or 90 days after the last study drug dose for partners of male 
subjects will be reported on the Pregnancy Report form and captured only in the safety database.  
The pregnancy will not be entered into the clinical database, allowing the database to be locked 
and the data analyzed. All further follow-up of the pregnancy through resolution (abortion either 
elective or spontaneous, fetal demise, still birth, or live birth) will be captured on Pregnancy 
Confirmation and Outcome Forms and entered only into the safety database. 
All pregnancy information including any follow up known at that time will be reported in the 
annual safety reporting required for a product in development. In the United States, this is met by 
the FDA required IND annual report or the DSUR if waiver is obtained from the FDA. In the 
European Union this is met by the European Medicines Agency (EMA) required DSUR. 
11.4.8. 
Urgent Safety Measures 
If the CRU or any of its staff or contractors becomes aware of an actual or potential urgent safety 
issue, then the Sponsor must be immediately contacted so that appropriate urgent safety 
measures can be agreed upon. An urgent safety issue is defined as:  
• An immediate hazard to the health or safety of subjects participating in a clinical 
study 
• A serious risk to human health or potentially a serious risk to human health 
An urgent safety issue may include issues with an investigational drug or comparators, study 
procedures, inter-current illness (including pandemic infections), concomitant medications, 
concurrent medical conditions, or any other issues related to the safe conduct of the study or that 
pose a risk to study subjects. 


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In exceptional circumstances of imminent hazard and in order to safeguard the health or safety of 
individuals, the CRU may take urgent safety measures before informing the Sponsor, but the 
Sponsor must be informed immediately after the hazard has resolved.  
The Sponsor will take responsibility for informing appropriate competent authorities, 
Investigators, and IRB. 
11.4.9. 
Reporting of Urgent Safety Issues 
The Sponsor is required to inform the appropriate competent authorities, Investigators, and IRB 
within 3 calendar days of the urgent safety issue. 
11.4.10. 
Serious Breaches 
It is the responsibility of the Sponsor to notify the licensing authority of any serious breach that 
is likely to affect, to a significant degree, the safety or mental integrity of the subjects in the 
study or the scientific value of the study. 
11.5. 
Safety Oversight 
Safety oversight will be provided by the means of an ISM, a DEC, and an SMC. 
11.5.1. 
Independent Safety Monitor 
The investigative site will have a physician ISM who is not part of the clinical study staff and has 
no direct study responsibilities. The ISM’s responsibility will be the review of all SAEs and if 
needed, any AEs of special interest. The ISM may use all available data at the site including 
examination of the subject. The ISM will summarize his/her findings in a report that will be 
forwarded to the DEC and the SMC within 24 hours of the event. 
The ISM must be available during the entire duration of the study or a back-up must be identified 
and available during the primary ISM’s absence.  
11.5.2. 
Dose Escalation Committee 
Following the completion of each cohort, the DEC will meet to decide if the required safety 
parameters have been met.  All available safety data for all subjects in a given cohort through 
96 hours and PK data through 24 hours post-dose will be reviewed by the Sponsor Medical 
Monitor, Clinical Pharmacologist, and PI and used in the decision to escalate to the next higher 
dose. Review meetings will be held following each dose level of Cohorts 1 to 4.  
An interim Safety Summary Report will be prepared for review by the DEC that will document 
the following safety findings for each dose cohort: 
• Demographics 
• Dosing information, including any subjects who discontinued dosing 
• Listing of any SAEs with assessment of severity 
• Listing of AEs with assessment of severity 
• Listing of any graded clinical chemistry findings 


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• Listing of all clinical chemistry findings Grade 2 or higher 
• Listing of any graded hematology findings  
• Listing of all hematology findings 
• Listing of any graded urinalysis findings  
• Listing of all urinalysis findings 
• Listing of vital signs 
• Listing of QT findings  
• Telemetry findings 
• Additional narrative summaries 
• Listing of subjects who terminated early 
• Listing of PE data 
An interim PK report will be prepared for review by the DEC that will document the following 
PK findings for each dose cohort: 
• Preliminary plasma PK parameters (through 24-hours post-dose) based upon nominal 
times: AUC; Cmax, Tmax, terminal elimination half-life (t1/2; median, minimum, 
maximum, geometric mean, coefficient of variation [CV%])  
• Predictions of Cmax and AUC values for the next cohort, where relevant 
The interim Safety Summary and PK report documents will form the basis of teleconferences 
involving the Sponsor and the PI to evaluate each completed cohort in the study.  The DEC will 
use the Dose Escalation Criteria to determine whether escalation as planned per protocol may 
commence. 
Dose Escalation Criteria 
The study will proceed to the next planned dose level if NONE of the following is met: 
• One or more subjects with a treatment-emergent QT interval corrected by Fridericia's 
formula (QTcF) > 480 ms (Grade 2 per the DMID scale) as determined from bedside 
ECGs (with repeat ECG). If this occurs, the SMC may consult with an independent 
cardiologist as needed.  If it is deemed acceptable to restart the study following 
review of the data and discussion with an independent cardiologist, if needed, dosing 
may resume. 
• One or more subjects experiences an increase in BP that requires acute treatment, or 
has a confirmed systolic BP > 160 mmHg, or a confirmed diastolic BP > 100 mmHg 
(Grade 3 per DMID scale). Confirmed BP changes require at least 2 measurements at 
least 2 hours apart, each measured after at least 5 minutes of supine rest. 
• Anaphylactic reaction occurs in one subject. 


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• One or more subjects experience a similar Grade 3 treatment-emergent laboratory 
abnormality or AE that is suspected to be drug-related as determined by the 
investigator. 
• One subject experiences an SAE. 
• A cohort’s median AUC24 is ≥ 52,500 ng.h/mL, equivalent to the NOAEL exposure 
in cynomolgus monkeys.   
If any of the above criteria are met, escalation to the next planned dose cohort will not proceed 
until all available study data have been reviewed by the independent SMC, as per Section 11.5.3. 
If, following review by the SMC (Section 11.5.3) it is deemed acceptable to restart the study, 
dosing will resume.  All relevant data will be submitted to the regulatory authorities and IRB. 
11.5.3. 
Safety Monitoring Committee 
A SMC will be assembled for this study. The SMC membership is determined by NIAID, who is 
also responsible for the Charter. The SMC will review reports provided by the PI and Sponsor as 
outlined in the Charter and agreed upon in the organizational meeting. 
The SMC will meet to review all available safety and PK data from the study on the following 
occasions: when study halting criteria are met, when dose escalation could not be approved by 
the DEC, or when the criteria for not dosing additional subjects in a cohort are met after the 
sentinel subjects are dosed. A final SMC meeting will occur approximately 6 to 8 months 
following clinical database lock to review the cumulative unblinded safety data for the study.  
Data for all SMC meetings will be provided in a standard summary format. The SMC may be 
asked to provide recommendations in response to questions posed by DMID. Additionally, 
following the administration of Cohort 4 and a review of the PK and safety data by the SMC, the 
Sponsor may make a recommendation to enroll additional cohorts in the SAD to further 
characterize the safety, tolerability and PK of galidesivir. This additional enrollment will only 
occur provided that the PK is increasing predictably in proportion with increasing dose, no safety 
concerns have arisen or stopping criteria have been met, the exposure is below the NOEAL 
exposure identified in NHP studies, and with recommendation by the SMC. The protocol will be 
amended to enable the enrollment of any SAD cohorts after Cohort 4. 
The recommendations and final minutes of any SMC meeting will be supplied to the Sponsor, 
FDA and IRB, as applicable. 
12. 
STATISTICS 
12.1. 
Study Hypothesis 
No formal study hypothesis will be stated or tested in this Phase 1 study. 
12.2. 
Sample Size Considerations 
No formal power or sample size calculations were used to determine cohort sizes. Cohort sizes 
were based upon experience in other SAD Phase 1 studies. A sample size of 6 subjects receiving 


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active drug per cohort should provide adequate characterization of PK and safety assessments 
within this setting. 
12.3. 
Final Analysis Plan 
12.3.1. 
Statistical Methods 
A detailed Statistical Analysis Plan (SAP) will be developed and finalized prior to database lock. 
The SAP will describe the methods of analyses/summaries, including all endpoints, time points, 
populations, missing data, etc. Any deviation from the analyses outlined in the SAP will be 
described in the final CSR. 
12.3.1.1. Analysis Populations 
The analysis populations are defined below. Data from placebo-treated subjects will be pooled 
across cohorts.   
Safety Population 
The safety population will include all randomized subjects who received any amount of study 
drug (ie, a partial infusion). Subjects will be analyzed according to the treatment received. This 
population will be used for all analyses of accountability, demographics, galidesivir drug 
concentration, and safety. 
Pharmacokinetic Population 
The PK population will include all subjects for whom PK parameters can be estimated. The PK 
population will be the primary population for the PK analysis. 
12.3.1.2. Subject Demographic and Disposition Data 
Subject disposition will be presented for all subjects. The number of subjects who completed the 
study and discontinued from the study will be provided. All pertinent subject demographics will 
be presented using descriptive statistics. The reasons for early discontinuation will be presented. 
12.3.1.3. Analysis of Safety Variables 
AEs will be mapped to a Medical Dictionary for Regulatory Activities (MedDRA) preferred 
term (PT) and system organ classification (SOC). Any event reported on the subject’s study 
record that occurs on or after the initiation of study drug is defined as treatment emergent. 
Additionally, it is assumed that an AE that is reported to have started on Day 1 of a given 
treatment period without an associated onset time may have occurred after the initiation of study 
drug. Hence, AEs occurring on Day 1 with no associated onset time will be assumed to be 
treatment emergent. The occurrence of TEAEs will be summarized by cohort and treatment 
assignment using MedDRA PTs, SOCs, and severity. Separate summaries of treatment-emergent 
SAEs and AEs considered to be related to study drug will be generated. All AEs will be listed for 
individual subjects showing both verbatim and preferred terms.  
Descriptive summaries of vital signs, ECG parameters (12 lead and telemetry), ECHOs, and 
clinical laboratory results will be presented separately for each cohort by study visit and 
treatment assignment. Laboratory abnormalities will be graded according to the modified DMID 
criteria (APPENDIX A).  


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Any graded abnormality that occurs following the initiation of study drug and represents at least 
one grade increase from the baseline assessment is defined as treatment emergent. The number 
and percentage of subjects experiencing treatment-emergent graded toxicities will be 
summarized by treatment group. Laboratory toxicity shifts from baseline to post-baseline 
assessments will be summarized by treatment group.  
PE results will be presented in listings. Changes in PE results that are AEs will be reported in AE 
tables. 
Concomitant medications will be coded using the World Health Organization (WHO) 
Dictionary. These data will be summarized by cohort and treatment assignment. 
Subjects receiving placebo will be pooled and reported together across cohorts. 
12.3.1.4. Pharmacokinetic Analysis 
Concentrations of galidesivir will be determined by validated plasma and urine assays and will 
be summarized by treatment and displayed in figures. Plasma PK parameters for each subject 
will be estimated over the sampling interval using noncompartmental analysis (Phoenix 
WinNonlin Version 7.0 or higher, Certara) and summarized by treatment group using descriptive 
statistics. The amount and percentage of galidesivir excreted in the urine will be assessed at all 
doses. If possible, data will be summarized by cohort and dose proportionality assessed. 
The PK parameters that will be estimated for galidesivir are listed in Table 9. Additional 
analyses may be conducted as appropriate.  
Table 9: 
Pharmacokinetic Parameters 
Pharmacokinetic 
Parameter 
Definition 
AUCinf 
Area under the concentration versus time curve extrapolated to 
infinite time, calculated as AUClast + (Clast/λz) 
AUCt 
Area under the concentration versus time curve from time zero to 
time “t”; may be denoted as AUClast if the “t” is the last timepoint 
with a measurable concentration 
% AUCexp  
Percentage of AUC extrapolated between AUClast and AUCinf 
Clast 
Last measurable concentration of drug 
Cmax 
Maximum observed concentration of drug 
t1/2 
Estimate of the terminal elimination half-life of the drug 
CL 
CL = Dose/AUC 
where “Dose” is the dose of the drug and AUC = AUCinf  
λz 
Terminal elimination rate constant, estimate by linear regression of 
the terminal elimination phase of the concentration of drug versus 
time curve 
Vz 
Volume of distribution of the drug 
Tmax 
Time to Cmax 
CLr 
Renal clearance of unchanged drug in a specific interval 
(CLr [interval]) or cumulatively over all collection intervals 
% Doseexcreted 
Percentage of given dose excreted in the urine as unchanged drug 


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In all derivations of PK parameters, zero will be substituted for concentrations below the 
quantitation limit (BQL) of the assay.  Samples that are BQL, but are between two samples with 
detectable concentrations will be excluded from PK analysis. 
12.3.1.5. Dose Proportionality of Galidesivir 
Dose proportionality will be evaluated over all doses and will be based upon AUCinf, AUCt, and 
Cmax using both the power model and the analysis of variance ANOVA method. 
12.3.1.5.1. Power Model 
The power model is as follows: 
Equation 1: 
log(Yik) = Si[1] +β × log (Dosek) + εik  
where Yik is the measured response variable, AUCinf, AUCt, and Cmax, on the kth dose, 
Si[1] is random subject effect for the ith subject, and εikis the random error.  After 
exponentiation, the model equation 1 is identical to equation 2 (below). 
Equation 2: 
Yik = α × Doseβ 
 
where α includes the error.  
Dose proportionality for PK parameters will be assessed by restricted maximum likelihood using 
SAS PROC MIXED. The mean slope will be estimated from the power model and the 
corresponding 90% CI calculated. 
12.3.1.5.2. Analysis of Variance 
Following log-e transformation, dose-normalized PK parameters will be analyzed with an 
ANOVA model using PROC MIXED. Each dose will be compared with a reference dose on a 
pair-wise basis. The ratio of GLS means and the corresponding 90% CI will be estimated for 
each PK parameter of interest.  
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The study site will maintain appropriate medical and research records for this study, in 
compliance with International Council for Harmonisation (ICH) E6, Section 4.9 and regulatory 
and institutional requirements for the protection of confidentiality of subjects. 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction and evaluation of the study. 
Examples of these original documents and data records include, but are not limited to, 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, 


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microfilm or magnetic media, x-rays, and subject files and records kept at the pharmacy, at the 
laboratories, and at medico-technical departments involved in the clinical study.  
The site will permit authorized representatives of the Sponsor, DMID, and 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. 
13.1. 
Study Monitoring 
Before an investigational site can enter a subject into the study, a representative of BioCryst (this 
may include a representative from a contract-research organization) will visit the investigational 
study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities regarding 
protocol adherence, and the responsibilities of BioCryst or its representatives. 
During the study, the representative acting on behalf of BioCryst will have regular contacts with 
the investigational site for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• Perform source data verification. This includes a comparison of the data in the case 
report forms with the subject’s medical records at the hospital or practice, and other 
records relevant to the study. This will require direct access to all original records for 
each subject (e.g. clinic charts). 
• Record and report any protocol deviations not previously sent to BioCryst. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any 
SAEs have been forwarded to BioCryst and those SAEs that met criteria for reporting 
have been forwarded to the IRB. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
Site monitoring of this study will be conducted, as described in the study-specific Site 
Monitoring Plan, to ensure that human subject protection, study procedures, laboratory, study 
intervention administration, and data collection processes are of high quality and meet the 
Sponsor, ICH E6/GCP, and regulatory guidelines.  
13.2. 
Audits and Inspections 
Authorized representatives of BioCryst, a regulatory authority, or an IRB may visit the study site 
to perform audits or inspections, including source data verification. The purpose of a BioCryst 
audit or inspection is to systematically and independently examine all study-related activities and 


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documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, GCP guidelines of the ICH, and any 
applicable regulatory requirements. The investigator should contact BioCryst immediately if 
contacted by a regulatory agency about an inspection. 
13.3. 
Institutional Review Board  
The principal investigator must obtain IRB approval for the investigation. Initial IRB approval, 
and all materials approved by the IRB for this study including the subject consent form and 
recruitment materials must be maintained by the investigator and made available for inspection. 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following Phase 1 Unit Clinical’s Quality Management, Quality System policy and standard 
operating procedures, the investigational site is responsible for conducting timely routine quality 
control and quality assurance activities to internally monitor study progress, compliance with the 
protocol, applicable regulations, and GCP (E6) guidelines.   
The PI will provide BioCryst with direct access to the study site, source data/documents, and 
reports for the purpose of monitoring and auditing by the Sponsor, and inspection by local and 
regulatory authorities.  
The PI is responsible for ensuring that all study personnel are appropriately trained prior to 
conducting any protocol procedures, and current and complete documentations are maintained on 
site.  
Clinical site monitors will verify that the clinical study is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements. Data Management and control processes specific to this study, along 
with all steps and actions taken regarding data management and data quality control, will be 
described in a Data Management Plan. 
An explanation will be given for all missing, unused, and spurious data in the relevant sections of 
the CSR. 
15. 
ETHICS 
15.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB as appropriate. The investigator must submit written 
approval to BioCryst before he or she can enroll any subject into the study. 
The PI is responsible for informing the IRB of any amendment to the protocol in accordance 
with local requirements. In addition, the IRB must approve all advertising used to recruit subjects 
for the study. The protocol must be re-approved by the IRB upon receipt of amendments and 
annually, as local regulations require. 


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The PI is also responsible for providing the IRB with reports of any reportable serious adverse 
drug reactions from any other study conducted with the investigational product. BioCryst will 
provide this information to the PI. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
according to local regulations and guidelines. 
The IRB must be registered with the Office for Human Research Protections (OHRP) and must 
be designated on the research site’s Federal Wide Assurance (FWA).The IRB must provide 
written approval for the protocol and required documents (all handouts and forms given to or 
signed by the subject, all recruitment tools, all consent forms including screening, study, and 
pregnancy), prior to initiating any study related procedures, in compliance with the requirements 
of U.S. 45 CFR 46: Protection of Human Subjects, 21 CFR 56: Institutional Review Boards, and 
21 CFR 50: Protection of Human Subjects.  The ICF is viewed as an essential document that 
must be reviewed and approved by an IRB.   The Sponsor and PI are responsible for complying 
with the principles of GCP as specified in the ICH Harmonised Tripartite Guideline for GCP E6 
(R2). 
15.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements 
and BioCryst’s policy on Bioethics. 
15.3. 
Written Informed Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continuing throughout the individual’s study participation. Extensive discussion of 
risks and possible benefits of this therapy will be provided to the subjects. Consent forms 
describing in detail the study interventions/products, study procedures, and risks are given to the 
subject and written documentation of informed consent is required prior to starting 
intervention/administering study product. Consent forms will be IRB-approved and the subject 
will be asked to read and review the document. Upon reviewing the document, the PI or designee 
will explain the research study to the subject and answer any questions that may arise. The 
subjects will sign the ICF prior to any procedures being done specifically for the study including 
obtaining identifiable data from medical records. The subjects should have the opportunity to 
discuss the study with their surrogates or think about it prior to agreeing to participate. The 
subjects may withdraw consent at any time throughout the course of the study. A copy of the ICF 
will be given to the subjects for their records. The rights and welfare of the subjects 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. 
Subjects may be recruited from a generic screening protocol where they have been pre-screened 
for clinical studies by Phase 1 Unit Clinical and have signed a Generic Screening ICF.  
Procedures performed as part of the Phase 1 Unit Clinical generic screening protocol will be 
considered part of the subject’s medical history at Phase 1 Unit Clinical and the clinical or 
laboratory data may be used for screening and eligibility after informed consent for this study 
has been obtained. 


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15.3.1. 
Informed Consent/Assent Process (in Case of a Minor) 
Not applicable 
15.4. 
Exclusion of Women, Minorities, and Children (Special Populations) 
This study will be limited to adults aged 18 to 55 years due to the early stage of development and 
absence of any developmental or juvenile toxicity data. 
15.5. 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
the Sponsor and their agents. This confidentiality is extended to cover testing of biological 
samples in addition to the clinical information relating to participating subjects. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the Sponsor. 
The study monitor or other authorized representatives of the Sponsor may inspect all documents 
and records required to be maintained by the PI, 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. 
To protect privacy, the study site has 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 Federal 
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 him/herself or others.   
15.6. 
Study Discontinuation 
See Section 7.7. 
15.7. 
Future Use of Stored Specimens 
Not applicable. 


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15.8. 
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 study.  Procedures and treatment for clinical care may be billed to the subject, subject’s 
insurance or third party.  Subjects may be compensated for their participation in this study.  
Compensation will be in accordance with the local IRB’s policies and procedures, and subject to 
IRB approval. 
If it is determined by the study site PI that an injury occurred to a subject as a direct result of the 
tests or treatments that are performed in this study, then referrals to appropriate health care 
facilities will be provided to the subject.  Study personnel will try to reduce, control, and treat 
any complications from this study.  Immediate medical treatment may be provided by the 
participating site.  No financial compensation will be provided to the subject by the NIAID, NIH 
to the subject, or by the participating site for any injury suffered due to participation in this 
study. 
16. 
DATA HANDLING AND RECORDKEEPING 
The PI 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 ink is preferred to ensure clarity of reproduced copies, however blue 
ink is acceptable. 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. 
16.1. 
Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the clinical team and data 
entry staff, who will ensure that they are accurate and complete. AEs must be graded, assessed 
for severity and causality, and reviewed by the study site PI or designee. 
Data collection is the responsibility of the clinical study 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. 
The data coordinating center for this study at the CRO will be responsible for data management, 
quality review, analysis, and reporting of the study data. 
 
16.2. 
Data Capture Methods 
Clinical data (including AEs and concomitant medications) and clinical laboratory data will be 
entered into a 21 CFR Part 11-compliant Data Entry System. The data system includes password 
protection and internal quality checks, such as automatic range checks, to identify data that 
appear inconsistent, incomplete, or inaccurate.  
16.3. 
Types of Data 
Data for this study will include safety, laboratory, and PK data. 


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16.4. 
Timing/Reports 
Data from each cohort will be reviewed in a Dose Escalation Committee meeting in accordance 
with the procedures described in Section 11.5.2.  
16.5. 
Inspection of Records 
BioCryst will be allowed to conduct site visits to the investigation facilities for monitoring any 
aspect of the study. The investigator agrees to allow the monitor to inspect the drug storage area, 
study drug stocks, drug accountability records, subject charts and study source documents, and 
other records relative to study conduct. 
16.6. 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or BioCryst, the PI agrees to 
keep records, including the identity of all participating subjects (sufficient information to link 
records, eCRFs, and medical/hospital records), all original signed ICFs, all eCRFs, and detailed 
records of study drug accountability and treatment disposition. 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. The records should be retained by the PI according to local regulations or as specified in 
the Clinical Trial Agreement, whichever is longer. 
If the PI relocates, retires, or for any reason withdraws from the study, the study records may be 
transferred to an acceptable designee, such as another investigator, another institution, or to 
BioCryst. The PI must obtain BioCryst’s written permission before disposing of any records. 
16.7. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol, GCP, or Manual of 
Procedures requirements. The noncompliance may be either on the part of the subject, the PI, or 
the study site staff. Deviations from the protocol will be recorded in the source workbook as 
noted by the clinical staff. The Sponsor will be informed of the deviation. As a result of 
applicable 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. 
Protocol deviations must be sent to the local IRB per the IRB guidelines. The study site PI/study 
staff is responsible for knowing and adhering to the IRB requirements. 


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17. 
PUBLICATION POLICY 
All data generated from this study are the property of BioCryst and shall be held in strict 
confidence along with all information furnished by BioCryst. Independent analysis and/or 
publication of these data by the PI or any member of his/her staff are not permitted without prior 
written consent of BioCryst. Written permission to the PI will be contingent on the review by 
BioCryst of the statistical analysis and manuscript and will provide for nondisclosure of 
BioCryst confidential or proprietary information. In all cases, the parties agree to submit all 
manuscripts or abstracts to all other parties 30 days prior to submission. This will enable all 
parties to protect proprietary information and to provide comments based on information that 
may not yet be available to other parties. 
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 the following: 
• 
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 studies 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 studies 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 studies 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 SAP 
will be posted on ClinicalTrials.gov. 
For this study the responsible party is BioCryst which will register the study and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to the following: 
• 
Public Law 110-85, Section 801, Clinical Trial Databases 
• 
42 CFR Part 11 
• 
NIH NOT-OD-16-149 
 


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18. 
LIST OF REFERENCES 
Alcami (2016). "IV Administration and Dilution Study of BCX4430 Injection, 100 mg/mL, 
Diluted in 5% Dextrose, 0.9% Sodium Chloride and Lactated Ringer's to 1.0 and 15 mg/mL." 
Bray, M., K. Davis, T. Geisbert, C. Schmaljohn and J. Huggins (1999). "A mouse model for 
evaluation of prophylaxis and therapy of Ebola hemorrhagic fever." J Infect Dis 179 Suppl 1: 
S248-258. 
CDC. (2014). "CDC: Marburg Hemorrhagic Fever Fact Sheet."   Retrieved October 3, 2014, 
from 
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/fact_sheets/fact_sheet_marburg_hemorr
hagic_fever.pdf. 
Changula, K., M. Kajihara, A. S. Mweene and A. Takada (2014). "Ebola and Marburg virus 
diseases in Africa: increased risk of outbreaks in previously unaffected areas?" Microbiol 
Immunol 58(9): 483-491. 
Cross, R. W., C. E. Mire, H. Feldmann and T. W. Geisbert (2018). "Post-exposure treatments for 
Ebola and Marburg virus infections." Nat Rev Drug Discov. 
DHHS (2017). "Clinical Drug Interaction Studies - Study Design, Data Analysis, and Clinical 
Implications: Guidance for Industry: Draft Guidance." 
Julander, J. G., S. Bantia, B. R. Taubenheim, D. M. Minning, P. Kotian, J. D. Morrey, W. P. 
Sheridan and Y. S. Babu (2012). "BCX4430, an adenosine analog, with potent activity against 
yellow fever virus in a hamster model." 2nd Antivirals Congress. Cambridge, MA. 
Julander, J. G., S. Bantia, B. R. Taubenheim, D. M. Minning, P. Kotian, J. D. Morrey, D. Smee, 
W. P. Sheridan and Y. S. Babu (2014). "BCX4430, a novel nucleoside analog, effectively treats 
yellow fever in a hamster model." Antimicrobial Agents and Chemotherapy in press. 
Kuhn, J. H., L. E. Dodd, V. Wahl-Jensen, S. R. Radoshitzky, S. Bavari and P. B. Jahrling (2011). 
"Evaluation of perceived threat differences posed by filovirus variants." Biosecur Bioterror 9(4): 
361-371. 
Lund, K. C., L. L. Peterson and K. B. Wallace (2007). "Absence of a universal mechanism of 
mitochondrial toxicity by nucleoside analogs." Antimicrob Agents Chemother 51(7): 2531-2539. 
Warfield, K. L., S. B. Bradfute, J. Wells, L. Lofts, M. T. Cooper, D. A. Alves, D. K. Reed, S. A. 
VanTongeren, C. A. Mech and S. Bavari (2009). "Development and characterization of a mouse 
model for Marburg hemorrhagic fever." J Virol 83(13): 6404-6415. 
Warren, T. K., J. Wells, R. G. Panchal, K. S. Stuthman, N. L. Garza, S. A. Van Tongeren, L. 
Dong, C. J. Retterer, B. P. Eaton, G. Pegoraro, S. Honnold, S. Bantia, P. Kotian, X. Chen, B. R. 
Taubenheim, L. S. Welch, D. M. Minning, Y. S. Babu, W. P. Sheridan and S. Bavari (2014). 
"Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue 
BCX4430." Nature 508(7496): 402-405. 
WHO (2017). "Marburg virus disease." 
 
 


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APPENDICES 


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APPENDIX A:  TOXICITY TABLE – MODIFIED DMID ADULT 
TOXICITY TABLE, 2014 
Clinical Adverse 
Events 
 
 
 
VITAL SIGNS 
 Mild  
(Grade 1) 
 Moderate (Grade 2)  Severe  
(Grade 3)  
Fever (°C) ** 
38.0 – 38.4 
38.5 – 38.9 
≥39.0 
             (°F) ** 
100.4 – 101.1 
101.2 – 102.0 
>102.0 
** Oral temperature; no recent hot or cold beverages or smoking. A protocol should 
select either °C or °F for inclusion. 
Tachycardia - 
beats per minute 
101 – 115 
116 – 130 
> 130 or ventricular 
dysrhythmias 
Bradycardia - 
beats per minute 
50 – 54 or 45-50 
bpm if baseline 
<60 bpm 
45 – 49 or 40-44 if 
baseline <60bpm 
< 45 or  <40bpm if 
baseline <60bpm 
 Hypertension# 
(systolic)- mm Hg 
141-150 
151-160 
> 160 
Hypertension# 
(diastolic) - mm 
Hg 
91-95 
96-100 
> 100 
# Assuming supine position, 10 min at rest conditions, not sleeping subjects, 
measurements on the same arm and several concordant results. 


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 Hypotension 
(systolic) - mm 
Hg 
85-89 
80-84 
< 80 
Tachypnea – 
breaths per minute 
23-25 
26-30 
>30 
CARDIOVASCU
LAR 
 Grade 1  
 Grade 2  
 Grade 3  
 Arrhythmia 
   
 asymptomatic, 
transient signs, no Rx 
required  
 
recurrent/persistent; 
symptomatic Rx 
required  
QTcF interval 
prolonged (msec) 
Asymptomatic, 
QTcF >450-480 
msec 
Asymptomatic, QTcF 
>480-500 msec OR 
increase in interval 
30-60 msec from 
baseline 
Asymptomatic, 
QTcF >500 msec 
OR increase in 
interval >60 msec 
from baseline 
 Hemorrhage, 
Blood Loss  
  Estimated blood 
loss < 100 mL  
Estimated blood loss 
> 100 mL, no 
transfusion required 
Transfusion 
required  
 
RESPIRATORY   
 Grade 1  
 Grade 2  
 Grade 3  
 Cough  
 Transient- no 
treatment  
 Persistent cough;  
 Interferes with 
daily activities 
Bronchospasm, 
Acute 
 transient; no 
treatment; 71% - 
80% FEV1 of peak 
flow  
 requires treatment; 
normalizes with 
bronchodilator; FEV1 
60% - 70% (of peak 
flow)  
 no normalization 
with 
bronchodilator; 
FEV1 <60% of 
peak flow 
Dyspnea   
Does not interfere 
with usual and 
social activities 
Interferes with usual 
and social activities, 
no treatment 
Prevents daily and 
usual social activity 
or requires 
treatment 
GASTROINTES
TINAL   
 Grade 1  
 Grade 2  
 Grade 3  
 Nausea  
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activities 
 Vomiting  
No interference 
with activity or 1 - 
2 episodes/24 
hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily 
activity or requires 
IV hydration 


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 Diarrhea  
2 - 3 loose or 
watery stools or < 
400 gms/24 hours 
4 - 5 loose or watery 
stools or 400 - 800 
gms/24 hours 
6 or more loose or 
watery stools or > 
800gms/24 hours or 
requires IV 
hydration 
SYSTEMIC  
 Mild 
(Grade 1)  
 Moderate 
(Grade 2)  
 Severe 
(Grade 3)  
 Allergic 
Reaction/Hyperse
nsitivity  
 pruritus without 
rash  
 localized urticaria  
 generalized 
urticaria; 
angioedema or 
anaphylaxis  
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 
Myalgia 
No interference 
with activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
All Other 
conditions 
 Mild  
(Grade 1) 
 Moderate (Grade 2) 
 Severe  
(Grade 3)  
Illness or clinical 
adverse event (as 
defined according 
to applicable 
regulations) 
 Transient or mild 
symptoms; no 
limitation in 
activity; no 
intervention 
required. The AE 
does not interfere 
with the 
participant’s 
normal functioning 
level. It may be an 
annoyance. 
 Symptom results in 
mild to moderate 
limitation in activity; 
no or minimal 
intervention required. 
The AE produces 
some impairment of 
functioning, but it is 
not hazardous to 
health. It is 
uncomfortable or an 
embarrassment. 
 Symptom results in 
significant 
limitation in 
activity; medical 
intervention may be 
required. The AE 
produces significant 
impairment of 
functioning or 
incapacitation. 


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Laboratory Adverse 
Events 
 
  
  
  
Blood, Serum, or 
Plasma * 
Reference Range ** 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Sodium – Hyponatremia 
mEq/L 
135-146 mmol/L 
134 – <LLN 
132 – 133 
<132 
Sodium – Hypernatremia 
mEq/L 
135-146 mmol/L 
>ULN – 147 
148 – 149 
>149 
Potassium – 
Hyperkalemia mEq/L 
3.5-5.3 mmol/L 
>ULN – 5.4 
5.5 – 5.6 
>5.6 
Potassium – 
Hypokalemia mEq/L 
3.5-5.3 mmol/L 
<LLN-3.4 
<3.4 – 3.3 
<3.3 
Glucose – Hypoglycemia 
mg/dL 
65-99 mg/dL 
62 – 64 
52 – 62 
<52 
Glucose – 
Hyperglycemia  
Fasting – mg/dL 
65-99 mg/dL 
>ULN - 100 
101 – 110 
>110 
Glucose – 
Hyperglycemia  
Random – mg/dL 
65-139 mg/dL 
140 – 159 
160 – 200 
>200 
Blood Urea Nitrogen 
mg/dL 
7-25 mg/dL 
26 – 29 
30 – 34 
>34 
Creatinine (Male) – 
mg/dL 
18Y-19Y 
 
20Y-49Y 
 
50Y-59Y 
 
0.60-1.26 
mg/dL 
0.60-1.35 
mg/dL 
0.70-1.33 
mg/dL 
>ULN – 1.36 
 
>ULN – 1.45 
 
>ULN – 1.43 
 
>1.36 – 1.56 
 
>1.45 – 1.65 
 
>1.43 – 1.63 
 
>1.56 
 
>1.65 
 
>1.63 
Creatinine (Female)- 
mg/dL 
18Y-19Y 
 
20Y-49Y 
 
50Y-59Y 
0.50-1.00 
mg/dL 
0.50-1.10 
mg/dL 
0.50-1.05 
mg/dL 
>ULN – 1.10 
 
>ULN – 1.20 
 
>ULN – 1.15 
 
>1.10 – 1.30 
 
>1.20 – 1.40 
 
>1.15 – 1.35 
>1.30 
 
>1.40 
 
>1.35 
Calcium – hypocalcemia 
mg/dL (Male) 
18Y-19Y 
 
20Y-
133Y 
 
8.9-10.4 
mg/dL 
8.6-10.3 
mg/dL 
8.8 – <LLN 
 
8.5 – <LLN 
8.3 – 8.7 
 
8.0 – 8.4 
<8.3 
 
<8.0 
Calcium – hypocalcemia 
mg/dL (Female) 
18Y-19Y 
 
20Y-49Y 
 
8.9-10.4 
mg/dL 
8.6-10.2 
mg/dL 
8.8 – <LLN 
 
8.5 – <LLN 
 
 
8.3 – 8.7 
 
8.0 – 8.4 
 
 
<8.3 
 
<8.0 
 
 


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50Y-
133Y 
8.6-10.4 
mg/dL 
8.5 – <LLN 
8.0 – 8.4 
<8.0 
Calcium – 
hypercalcemia mg/dL 
(Male) 
18Y-19Y 
 
20Y-
133Y 
8.9-10.4 
mg/dL 
8.6-10.3 
mg/dL 
>ULN – 10.5 
 
>ULN – 10.4 
10.6 – 11.0 
 
10.5 – 10.9 
>11.0 
 
>10.9 
 
Calcium – 
hypercalcemia mg/dL 
(Female) 
18Y-19Y 
 
20Y-49Y 
 
50Y-
133Y 
8.9-10.4 
mg/dL 
8.6-10.2 
mg/dL 
8.6-10.4 
mg/dL 
>ULN – 10.5 
 
>ULN – 10.3 
 
>ULN – 10.5 
10.6 – 10.9 
 
10.4 – 10.7 
 
10.6 – 10.9 
 
>10.9 
 
>10.7 
 
>10.9 
 
Magnesium – 
hypomagnesemia mg/dL 
1.5-2.5 mg/dL 
1.3 – 1.5 
1.1 – 1.2 
<1.1 
Phosphorous – 
hypophosphatemia 
mg/dL 
18Y-64Y 
 
65Y-
133Y 
2.5-4.5 
mg/dL 
2.1-4.3 
mg/dL 
2.3 – <2.5 
 
1.9 – <2.1 
2.0 – < 2.2 
 
1.6 – < 1.8 
<2.0 
 
<1.6 
CPK – U/L (male) 
<196 
196 – 1000 
 
1001-1500 
>1500 
CPK – U/L (female) 
<143 
143 – 1000 
1001-1500 
>1500 
Albumin – 
Hypoalbuminemia g/dL 
3.6-5.1 g/dL 
3.0 – 3.5 
2.7 – 2.9 
<2.7 
Total Protein – 
Hypoproteinemia g/dL 
18Y-19Y 
20Y-
133Y 
6.3-8.2 
g/dL 
6.1-8.1 
g/dL 
6.1 – 6.3 
5.9 – 6.1 
5.7 – 6.0 
5.5 – 5.8 
<5.7 
<5.5 
Alkaline phosphatase – 
U/L (Male) 
18Y-19Y 
20Y-
133Y 
48-230 U/L 
40-115 U/L 
230 – 340 
115 – 225 
341 – 460 
226 – 345 
>460 
>345 
Alkaline phosphatase – 
U/L (Female) 
18Y-19Y 
20Y-49Y 
50Y-
133Y 
47-176 U/L 
33-115 U/L 
33-130 U/L 
176 – 286 
115 – 225 
130 – 240 
 
287 – 406 
226 – 345 
241 – 360 
>406 
>345 
>360 
AST (Male) U/L  
18Y-19Y 
20Y-49Y 
50Y-
133Y 
12-32 U/L 
10-40 U/L 
10-35 U/L 
32 – 93 
40 – 101 
35 – 96 
94 – 163 
102 – 171 
97 – 166 
>163 
>171 
>166 
AST (Female) U/L  
18Y-19Y 
20Y-44Y 
45Y-
133Y 
12-32 U/L 
10-30 U/L 
10-35 U/L 
32 – 93 
30 – 91 
35 – 96 
94 – 163 
92 – 161 
97 – 166 
>163 
>161 
>166 
ALT (Male) U/L  
18Y-19Y 
20Y-
133Y 
8-46 U/L 
9-46 U/L 
46 – 101 
46 – 101 
102 – 171 
102 – 171 
>171 
>171 
ALT (Female) U/L  
18Y-19Y 
5-32 U/L 
32 – 87 
88 – 157 
>157 


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20Y-
133Y 
6-29 U/L 
29 – 84 
85 – 154 
>154 
Bilirubin (serum total) 
mg/dL 
18Y-19Y 
 
20Y-
133Y 
0.2-1.1 
mg/dL 
0.2-1.2 
mg/dL 
1.2 – 1.9 
 
1.3 – 2.0 
2.0 - 2.4 
 
2.1 –  2.5 
>2.4 
 
>2.5 
Bilirubin – when ALT 
>105 (Hy's law) 
 
1.3 – 1.5 
1.6 – 2.0 
>2.0 
Amylase- U/L 
21 – 101 U/L 
102 – 177 
178 – 278 
>278 
Lipase- U/L 
7 – 60 U/L 
60 – 165 
166 – 250 
>250 
Hemoglobin (Male) - 
g/dL 
18Y 
 
19Y-
133Y 
12.0-16.9 
g/dL 
13.2-17.1 
g/dL 
11.5 – 12.0 
 
12.7 – 13.2 
10.5 – 11.9 
 
12.2 – 12.7 
<10.5 
 
<12.2 
Hemoglobin (Female) - 
g/dL 
18Y 
 
19Y-
133Y 
11.5-15.3 
g/dL 
11.7-15.5 
g/dL 
11.0 – 11.5 
 
11.2 – 11.7 
9.5 – 10.9 
 
9.8 – 11.2 
<9.5 
 
<9.8 
WBC Increase - 
cell/mm3 
18Y 
 
19Y-
133Y 
4,500-
13,000/uL 
3,800-
10,800/uL 
13,001 – 
17,000 
10,801 – 
14,800 
17,001 – 
22,000 
14,801 – 
19,800 
>22,000 
 
>19,800 
WBC Decrease - 
cell/mm3 
18Y 
 
19Y-
133Y 
4,500-
13,000/uL 
3,800-
10,800/uL 
3,500 – 
4,500 
2,800 – 
3,800 
2,500 – 
3,499 
1,800 – 
2,799 
<2,500 
 
<1,800 
Lymphocytes Decrease - 
cell/mm3 
18Y 
 
19Y-
133Y 
1200-5200 
cells/uL 
850-3900 
cells/uL 
950 – 1,200 
 
600 – 850 
700 – 949 
 
450  – 599 
<700 
 
<450 
Neutrophils Decrease - 
cell/mm3 
18Y 
 
19Y-
133Y 
1800-8000 
cells/uL 
1500-7800 
cells/uL 
1,300 – 
1,799 
1,000 – 
1,499 
1,049 – 
1,299 
750 – 999 
<1,049 
 
<750 
Eosinophils - cell/mm3 
15-500 cells/uL 
500 – 750 
751 – 1600 
>1600 
Platelets Decreased - 
cell/mm3 
140,000 – 400,000/ uL 
130,000 – 
140,000 
110,000 – 
129,999 
<110,000 
PT – seconds 
(prothrombin time) 
9.0-11.5 seconds 
> ULN-
14.4 
14.5 – 15.7 
>15.7 
PTT – seconds (partial 
thromboplastin time) 
22-34 sec 
>ULN-34.1 34.2– 42.0 
>42.0 
Fibrinogen increase - 
mg/dL 
175-425 mg/dL 
>ULN – 
425 
426 – 525 
>525 
Fibrinogen decrease - 
mg/dL 
175-425 mg/dL 
<LLN – 
175 
160 – 174 
<160 


Protocol BCX4430-106/DMID 18-0013 
 
Galidesivir, Version 3.0 
 
 
90 
 
  
 
  
Urine * 
 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 
3) 
Protein 
 
1+ 
2+ 
>2+ 
Glucose 
 
1+ 
2+ 
>2+ 
Blood (microscopic) - 
red blood cells per high 
power field (rbc/hpf) 
 
5-10 
11-50  
> 50 and/or 
gross blood 
 
* The laboratory values provided in the tables serve as guidelines and are dependent 
upon institutional normal parameters.  
 
* Institutional normal reference ranges should be provided to demonstrate that they 
are appropriate. 
 
** Reference ranges are from Quest Diagnostics. Any age range that is not specified 
is 18Y – 133Y 
 
 
 
 

SAP_001.pdf: 
* 
PRAHEALTHSCIENCES 
Statistical Analysis Plan 
Bl0139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Approvals 
Statistical Analysis Plan 
BioCryst Pharmaceuticals, Inc. 
BCX4430-106-DMID18-0013 
A phase 1 double-blind, placebo-controlled, dose-ranging study to 
evaluate the safety, tolerability, and pharmacokinetics of galidesivir 
(BCX4430) administered as single doses via intravenous infusion in 
healthy subjects 
8IO139GF-181392 
1 O-April-2019 
The undersigned have approved this Statistical Analysis Plan for use in this study. 
Name of Sponsor 
Representative I Title: 
iSignature of Sponso'r ; ' 
' ~epresenta_tive /Date: 
'Name of Sponsor 
Representative / Title: 
~Signature of Sponsor ' 
!.f:~epresentaUy~ I: Date: -
}Name oi Sponsor!'. 
· Representativ,e I Title_ 
· Signature of Sponsor 
Representative / Date: · 
Name of Sponso~ · 
R_epresentative /Title: · · 
Sharon C. Murray, PhD/ Director Biostatistics, BioCryst Pharmaceuticals 
~
C- ~
-
1/,Af~lot'i 
Diane Gesty-Palmer, MD / Senior Me~
ector, BioCryst 
Pharmaceuticals 
Elliott Berger, MD / Senior Vice President, Regulatory Affairs, BioCryst 
Pharmaceuticals 
Amanda Mathis, PhD / Director of Clinical Pharmacology 
';Signat~re of Sponsor;_'• I , 
·Representative/ Date:,·• I 
~~~me of AtJthorI-.Titie: · · Jacqueline Cater/ Senior Biostatistician, PRA Health Sciences 
' Signature of Author/ 
ID 
-
. 
L ate: . 
-·-
--
_, __ ..... _ 
._ ... -
...... - .. » - ... -
EDSREP 009 T 01 G 
Page 1 of 35 


* P RAHEA LTHSCIENCES 
Table of Contents 
Statistical Analysis Plan 
8IO139GF-181392 
Protocol: BCX4430-106-DM!D18-0013 
Version Date: 10-April-2019 
Approvals ....................................................................................................................................................... 1 
Table of Contents .......................................................................................................................................... 2 
3.0 lntroduction .............................................................................................................................................. 4 
4.0 Changes from Previous Version of Approved SAP ................................................................................ .4 
5.0 Study Objectives ...................................................................................................................................... 4 
5.1 Primary Objective ............................................................................................................................... .4 
5.1.1 Primary Endpoints ....................................................................................................................... .4 
5.2 Secondary Objective ........................................................................................................................... 4 
5.2.1 Secondary Endpoints ................................................................................................................... 4 
6.0 Study Design ........................................................................................................................................... 5 
6.1 Sample Size Considerations ............................................................................................................... 6 
6.2 Randomization ..................................................................................................................................... 6 
7.0 Overview of Planned Analysis ................................................................................................................. ? 
7.1 Changes from Protocol ........................................................................................................................ 7 
7.2 Interim Analysis and Key Results ........................................................................................................ 7 
7.3 Final Analysis ...................................................................................................................................... 7 
8.0 Data Review ............................................................................................................................................ 7 
8.1 Data Management ............................................................................................................................... 7 
8.2 Acceptance of Data for Summarization ............................................................................................... 7 
9.0 Definitions and General Analysis Methods ............................................................................................. 8 
9.1 Analysis Data Presentation ................................................................................................................. 8 
9.1.1 Rounding ...................................................................................................................................... 8 
9.1.2 Imputation ..................................................................................................................................... 8 
9.1.3 Descriptive Statistics .................................................................................................................... 8 
9.1.4 Pooling .......................................................................................................................................... 8 
9.1.5 Unscheduled Measurements ........................................................................................................ 8 
9.2 Analysis Data Definitions ..................................................................................................................... 8 
9.2.1 Baseline Definition ........................................................................................................................ 8 
9.2.2 Treatment/Subject Grouping ........................................................................................................ 9 
9.2.3 Common Variable Derivations ...................................................................................................... 9 
9.2.4 QC .............................................................................................................................................. 10 
9.2.5 ADaM Datasets and Metadata ................................................................................................... 10 
9.3 Software ............................................................................................................................................ 10 
9.4 Statistical Methods ............................................................................................................................ 1 o 
9.4.1 Statistical Outlier Determination ................................................................................................. 10 
9.4.2 Predetermined Covariates and Prognostic Factors ................................................................... 10 
9.4.3 Hypothesis Testing ..................................................................................................................... 10 
9.4.3.1 Primary Objective .................................................................................................................... 10 
9.4.3.2 Secondary Objective - Dose Proportionality ........................................................................... 10 
9.5 TFL Layout ........................................................................................................................................ 11 
10.0 Analysis Populations ........................................................................................................................... 11 
10.1 Safety Population ............................................................................................................................ 11 
10.2 Pharmacokinetic Population ............................................................................................................ 12 
11.0 Subject Disposition .............................................................................................................................. 12 
12.0 Protocol Deviations .............................................................................................................................. 12 
13.0 Demographic and Baseline Characteristics ........................................................................................ 12 
13.1 Demographics ................................................................................................................................. 12 
13.2 Medical History ................................................................................................................................ 12 
13.3 Screening Results ........................................................................................................................... 12 
14.0 Prior and Concomitant Medications .................................................................................................... 12 
15. 0 Treatment Exposure ............................................................................................................................ 12 
16.0 Pharmacokinetic Variables .................................................................................................................. 13 
16.1.1 Plasma Variables ...................................................................................................................... 13 
EDSREP 009 T 01 G 
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* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
16.1.2 Urine Variables ......................................................................................................................... 14 
16.2 Pharmacokinetic Summaries ........................................................................................................... 15 
16.2.1 Plasma Concentrations ............................................................................................................ 15 
16.2.2 Plasma Pharmacokinetic Parameters ...................................................................................... 15 
16.2.3 Urine Pharmacokinetic Parameters .......................................................................................... 16 
16.2.4 Dose Proportionality Analyses ................................................................................................. 16 
17. O Safety Analyses ................................................................................................................................... 17 
17 .1 Safety Variables .............................................................................................................................. 17 
17.1 .1 Adverse Events ........................................................................................................................ 18 
17.1.2 Deaths and Serious Adverse Events ........................................................................................ 18 
17 .1. 3 Laboratory Data ........................................................................................................................ 18 
17.1.4 Vital Signs ................................................................................................................................. 19 
17.1.5 Electrocardiograms ................................................................................................................... 19 
17.1.6 Cardiac Telemetry .................................................................................................................... 19 
17 .1. 7 Echocardiograms ...................................................................................................................... 19 
17 .1. 8 Physical Examination ............................................................................................................... 19 
References .................................................................................................................................................. 20 
Appendix 1: Glossary of Abbreviations ....................................................................................................... 21 
Appendix 2: Schedules of Assessments from Protocol ............................................................................... 23 
Appendix 3: List of End of Text Outputs ...................................................................................................... 26 
Appendix 4: Shells for Post-Text Tables, Figures and Listings ................................................................... 29 
Appendix 5: Toxicity Table - Modified DMID Adult toxicity Table, 2014 ..................................................... 29 
Document History ........................................................................................................................................ 35 
EDSREP 009 T 01 G 
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* PRAHEALTHSCIENCES 
3.0 Introduction 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
This Statistical Analysis Plan (SAP) describes the statistical methods that will be used during the analysis 
and reporting of data collected under BioCryst Pharmaceuticals, Inc., Protocol BCX4430-106. 
This SAP should be read in conjunction with the study protocol and electronic case report form (eCRF). 
This version of the SAP has been developed using the protocol dated 11-Jan-2019 and the final eCRF(s) 
dated 30-Oct-2018. 
An approved and signed SAP is a requirement for database lock. 
This SAP covers all results that will be processed by the PRA Early Development Services (EDS) 
Biostatistics Department. 
PRA EDS will perform the final pharmacokinetic (PK) and safety and tolerability analyses. 
This SAP supersedes the statistical considerations identified in the protocol; where considerations are 
substantially different, they are identified. Any post-hoc or unplanned analyses, or substantive changes 
from the planned analysis in this SAP performed to provide results for inclusion in the clinical study report 
(CSR), will be clearly identified in the CSR. Changes to planned analyses do not require an updated SAP 
but should be denoted in the CSR if significant. 
4.0 Changes from Previous Version of Approved SAP 
Not applicable. This is the first version of the SAP. 
5.0 Study Objectives 
5.1 Primary Objective 
The primary objective of the study is: 
• 
To evaluate the safety and tolerability of single ascending doses (SAD) of galidesivir (BCX4430) 
administered by intravenous (IV) infusion in healthy subjects. 
5.1.1 Primary Endpoints 
The primary endpoints of the study are: 
• 
Safety and tolerability parameters including adverse events (AEs) and serious adverse events 
(SAEs), laboratory abnormalities, vital signs, electrocardiograms (ECGs), echocardiograms 
(ECHOs), cardiac telemetry, and physical examination (PE). 
5.2 Secondary Objective 
The secondary objective of the study is: 
• 
To characterize the plasma pharmacokinetic (PK) profile and urinary elimination of SAD of 
galidesivir administered by IV infusion in healthy subjects. 
5.2.1 Secondary Endpoints 
The secondary endpoints of this study are: 
• 
The PK parameters for galidesivir, including: maximum concentration (Cmax}, last measurable 
concentration of drug (C1as1), time to maximum concentration (T max), area under the concentration 
time curve from time zero to last time (AUC1as1), area under the concentration time curve from time 
zero to infinity (AUCint}, clearance (CL), volume of distribution (Vz}, percentage of AUC extrapolated 
between AUC1as1 and AUCint (AUCextrap}, Az, and half-life (t1,2), and other parameters, where 
appropriate. 
EDSREP 009 T 01 G 
Page 4 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BI0139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
• 
Dose proportionality of galidesivir based upon AUCint, AUC from time O to time "t" (AUC1), and Cmax. 
6.0 Study Design 
This SAD study will evaluate the safety, tolerability, and PK of single doses of galidesivir vs. placebo 
administered as IV infusions in healthy subjects enrolled in up to four dose cohorts of 8 subjects each, for 
a total of 32 subjects. A single dose of study drug will be administered per cohort: 6 subjects will receive 
galidesivir IV, and 2 subjects will receive matching placebo. 
The planned cohorts are as follows: 
• 
Cohort 1, Regimen A: 5 mg/kg galidesivir or placebo, IV infusion x 1 dose 
• 
Cohort 2, Regimen B: 10 mg/kg galidesivir or placebo, IV infusion x 1 dose 
• 
Cohort 3, Regimen C: 15 mg/kg galidesivir or placebo, IV infusion x 1 dose 
• 
Cohort 4, Regimen D: 20 mg/kg galidesivir or placebo, IV infusion x 1 dose 
Subjects will be randomized within each cohort to receive either galidesivir or placebo. As a safety 
precaution, on the first day of dosing in each cohort, only 2 subjects will be dosed (to be referred to as 
sentinel subjects). The randomization schedule will be constructed such that 1 of the sentinel subjects 
dosed on the first day will be randomized to receive galidesivir and 1 will be randomized to receive 
placebo. After review of the safety data from the 24-hour post-dose period for the sentinel subjects, which 
includes review of any AEs, any abnormalities in the bedside ECGs, safety laboratory assessments and 
vital signs, the remainder of the cohort (5 subjects randomized to galidesivir; 1 randomized to placebo) 
will be dosed at least 2 days after the sentinel subjects. 
Enrollment of subjects in each sequential higher dose level cohort will occur only after completion of a 
clinical safety review of laboratory, AE, vital sign, ECG (12-lead and telemetry), and PE data for all 
subjects up through 96 hours post-dose and plasma PK data through 24 hours post-dose. Based upon 
safety review and evaluation of the data for each subject, adjustments in the dose escalation scheme for 
the next cohort may be made, including omission of higher dose cohorts in the event that the safety and 
PK parameters have been adequately characterized with lower dose cohorts. Where considered 
appropriate to meet the study objectives, adjustments in the protocol-specified dose escalation for 
subsequent cohorts are permissible (i.e., an intermediate dose between the previous tolerable dose and 
the scheduled next higher dose). The study design is shown in Figure 1 (below). 
EDSREP 009 T 01 G 
Page 5 of 35 


* 
PRAHEALTHSCIENCES 
Figure 1 BCX4430-106 Study Design 
28 day screening 
period 
Safety 
D-28 
• 
Dos
ing 
D-1 
PK • 
I 
D1 
Abbreviations: D = day; PK = phamiacokinetic. 
In Clinic 
6.1 Sample Size Considerations 
D4 
D5 
Statistical Analysis Plan 
BI0139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 O-April-2019 
D7 
D14 
PK/Safety review prior 
to 
escalation to 
next 
dose level occurs during 
this t ime frame 
Follow Up Visit 
• 
 
I 
021 
No formal power or sample size calculations were used to determine cohort sizes. Cohort sizes were 
based upon experience in other SAD Phase 1 studies. A sample s
ize of 6 subjects receiving active drug 
per cohort should provide adequate characterization of PK and safety assessments within this setting. 
6.2 Randomization 
This is a double-blind study; treatment assignment within a cohort will be blinded to the Pl, clinical staff, 
study subjects, and the data management team, with the exception of the unblinded dosing team, if 
required. The randomization schedules will be generated by an unblinded study statistician. A computer-
generated randomization schedule will be used to randomly assign subjects to galidesivir or placebo. 
Subjects in each of the Cohorts 1 to 4 will be randomized to galidesivir or placebo in a 3:1 ratio (ie, 6 
subjects per cohort will be randomly assigned to receive galidesivir and 2 subjects per cohort will be 
randomly assigned to receive placebo). As a safety precaution, on the first day of dosing in all cohorts, 
2 sentinel subjects will be initially dosed, and the randomization schedule will be generated so that in 
each cohort 1 sentinel subject is randomly assigned to receive galidesivir and 1 sentinel subject is 
randomly assigned to receive placebo. The remainder of the cohort will be randomized such that 
5 subjects are assigned to receive galidesivir and 1 subject assigned to receive placebo. 
EDSREP 009 T 01 G 
Page 6 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Following confirmation of eligibility, subjects will be identified by a unique 5-digit subject identifier (e.g., 
11001) in which the first digit indicates the study site identifier, the second digit indicates the cohort 
number and the final 3 digits indicate the subject number. Any replacement subjects will be identified by 
replacing the third digit "0" with "9". For example, if Subject 11005 withdraws from the study early, the 
replacement subject will be numbered 11905 and will receive the same study treatment (i.e., active or 
placebo) as Subject 11005. 
Subject numbers will be as follows: 
Cohort 
Subject Numbers 
1 
11001 to 11008 
2 
12001 to 12008 
3 
13001 to 13008 
4 
14001 to 14008 
7.0 Overview of Planned Analysis 
7 .1 Changes from Protocol 
There are no changes from the protocol. 
7 .2 Interim Analysis and Key Results 
Replacement Subject Numbers 
11901 to 11908 
12901 to 12908 
13901 to 13908 
14901 to 14908 
An interim PK report will be prepared by Biocryst for review by the DEC that will document the following 
PK findings for each dose cohort: 
• 
Preliminary plasma PK parameters (through 24-hours post-dose) based upon nominal times: 
AUC; Cmax, T max, terminal elimination half-life (t112; median, minimum, maximum, geometric 
mean, coefficient of variation [CV%]) 
• 
Predictions of Cmax and AUC values for the next cohort, where relevant 
7.3 Final Analysis 
Draft TFLs will be provided after database lock. After Sponsor comments have been incorporated, the TFLs 
will be finalized and incorporated into the first draft of the CSR. 
8.0 Data Review 
8.1 Data Management 
Data handling and transfer will take place under the PRA Data Management Plan for the study. 
8.2 Acceptance of Data for Summarization 
Programming of analysis datasets and TFLs may be ongoing during the data management of the study. 
However, programming of analysis datasets and TFLs will be completed and quality controlled (QC'd) after 
EDSREP 009 T 01 G 
Page 7 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
database lock. Only quality-assured results released by the Safety Laboratory, Bioanalytical Laboratory, or 
other external data source will be used for the programming of analysis datasets and TFLs for the final 
report. Any data values requiring investigation or corrections that are identified while programming the 
analysis datasets and TFLs will be sent to the project Data Manager. If the issue affects the TFLs the 
Programmer or Statistician who identified the issue will follow it to resolution. 
9.0 Definitions and General Analysis Methods 
9.1 Analysis Data Presentation 
9.1.1 Rounding 
In listings, data will be presented with the same precision as the original data. Derived data will be rounded 
for presentation purposes. 
For all summaries, minimum (min) and maximum (max) will be presented to the same number of decimal 
places as the original data, the mean and median to 1 decimal greater than the original data, and the 
standard deviation (SD) to 2 decimals greater than the original data. Frequency percentages and percent 
coefficient of variation (CV%) will be presented to 1 decimal. 
PK parameters will be rounded in the derived datasets as determined by the pharmacokineticist and 
presented as such in the listings. Each parameter will have a fixed number of decimals (Cmax and AUC will 
have 3 significant figures, and half-life and T max will have 1 decimal). In general, the pharmacokineticist will 
use discretion when deciding the number of decimals for each parameter. 
9.1.2 Imputation 
Unless otherwise noted, data will not be imputed. 
9.1.3 Descriptive Statistics 
Unless otherwise indicated, continuous variables will be summarized with the following descriptive 
statistics: n (number of observations}, (arithmetic) mean, SD, min, median, and max. 
Categorical data will be summarized with frequencies and percentages. Percentages by categories will be 
based on the number of subjects exposed within a treatment. Percentages will be rounded to 1 decimal, 
except 100% which will be displayed without any decimal places. Percentages will not be displayed for zero 
counts. Categories will be presented in the tables exactly as they appear in the eCRF / database. 
9.1.4 Pooling 
Placebo subjects will be pooled for summary TFLs for this study. 
9.1.5 Unscheduled Measurements 
Unscheduled measurements will be included in the listings. In general, except for unscheduled 
measurements used for baseline, unscheduled measurements will be excluded from the descriptive 
statistics and statistical analysis by timepoint. For shift tables or tables that summarize worst outcome, 
unscheduled measurements (occurring after previous timepoint and up to and including each scheduled 
timepoint) will be included in summary statistics. 
9.2 Analysis Data Definitions 
9.2.1 Baseline Definition 
Unless otherwise stated, baseline for post dose evaluations is defined as the last observation recorded 
before the first study drug administration for each regimen as indicated in Appendix 2 (Schedule of 
Assessments). The last observation can be an unscheduled/repeated measurement. Baseline ECGs will 
EDSREP 009 T 01 G 
Page 8 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID 18-0013 
Version Date: 1 O-April-2019 
be calculated from an average of the triplicate readings prior to initiation of treatment on Day 1 of each 
treatment period. 
9.2.2 Treatment/Subject Grouping 
Throughout this SAP, study drug refers to: BCX4430 galidesivir for IV infusion. 
Label 
! Grouping 
---------
Study Drugs 
Treatment 
Dose Levels 
BCX4430 galidesivir for IV infusion 
Cohort 1: 
Regimen A: Galidesivir (Dose 5 mg/kg, Calculated Dose Range 
250-500 mg, Concentration 1.0 mg/ml, Dose Volume 250-500 ml}, or 
Placebo (Dose Volume 250-500 ml) 
•• 
Regimen B: Galidesivir (Dose 10 mg/kg, Calculated Dose Range 
500-1000 mg, Concentration 1.0-2.0 mg/ml, Dose Volume 500 ml}, or 
Placebo (Dose Volume 500 ml) 
• • 
Regimen C: Galidesivir (Dose 15 mg/kg, Calculated Dose Range 
750-1500 mg, Concentration 1.5-3.0 mg/ml, Dose Volume 500 ml}, or 
• 
Placebo (Dose Volume 500 ml) 
Cohort 4: 
Regimen D: Galidesivir (Dose 20 mg/kg, Calculated Dose Range 
1000-2000 mg, Concentration 2.0-4.0 mg/ml, Dose Volume 500 ml), or 
Placebo (Dose Volume 500 ml) 
BCX4430: 5 mg/kg, Calculated Dose Range 250-500 mg 
BCX4430: 10 mg/kg, Calculated Dose Range 500-1000 mg 
BCX4430: 15 mg/kg, Calculated Dose Range 750-1500 mg 
BCX4430: 20 mg/kg, Calculated Dose Range 1000-2000 mg 
[Note: Treatment labels will use mg/kg] 
9.2.3 Common Variable Derivations 
Variable 
Data Type I Definition/Calculation 
Change from baseline 
All 
Analysis study day (prior to dose) 
All 
Analysis study day (post dose) 
All 
TEAE 
AE 
Post-dose observation minus baseline observation 
Date of measurement minus dose date 
Date of measurement minus dose date + 1 
An AE is a treatment-emergent adverse event 
(TEAE) if the AE start date/time is greater than or 
equal to the first dose date/time 
Abbreviations: AE = adverse event; TEAE = treatment-emergent adverse event. 
EDSREP 009 T 01 G 
Page 9 of 35 


* PRAHEALTHSCIENCES 
9.2.4 QC 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
The analysis datasets and the TFLs will be QC'd according to the PRA EDS QC plan. 
9.2.4.1 Critical Data 
The QC plan requires datasets be classified as critical or non-critical. As the primary and secondary 
objectives of this study are to characterize the safety and tolerability of galidesivir as well as PK profile, 
critical datasets include subject level demographics, PK parameters, concentrations, and AEs. 
9.2.5 ADaM Datasets and Metadata 
The analysis datasets will be generated in accordance with Clinical Data Interchange Standard Consortium 
(CDISC) Analysis Data Model (ADaM) Version 2.1. 
ADaM-compliant datasets will be delivered to the sponsor. A define.xml file Version 2 with the 
corresponding metadata will be included. Analysis results metadata are excluded. 
9.3 Software 
The statistical analysis and reporting will be done using SAS® for Windows™ Version 9.4 or higher (SAS 
Institute, Inc.). 
PK parameter calculations will primarily be done using Phoenix® WinNonlin® Version 8.1 or higher (Certara, 
Inc.). Additional PK computations may be performed in SAS. 
9.4 Statistical Methods 
9.4.1 Statistical Outlier Determination 
No statistical outlier analysis is planned. 
9.4.2 Predetermined Covariates and Prognostic Factors 
There are no predetermined covariates or prognostic factors. 
9.4.3 Hypothesis Testing 
9.4.3.1 Primary Objective 
No formal study hypothesis will be stated or tested in this Phase I study. 
9.4.3.2 Secondary Objective - Dose Proportionality 
Dose proportionality for AUCint, AUC1, and Crnax will be evaluated using the power model (including all doses) 
and also using an ANOVA model where each dose will be compared with a reference dose in a pairwise 
basis. The mean slope from the power model and the set of pairwise comparisons from the ANOVA method 
will constitute descriptive evaluations of dose proportionality. 
Power Model 
The power model is as follows: 
Equation 1: 
log(Yik) = S}11 +r3 x log (Dosek) + Eik 
where Yik is the measured response variable, AUCint, AUC1, and Crnax, on the kth dose, S}11 is 
random subject effect for the ith subject, and Eik is the random error. After exponentiation, the 
model equation 1 is identical to equation 2 (below). 
EDSREP 009 T 01 G 
Page 10 of 35 


* 
PRAHEALTHSCIENCES 
Equation 2: 
Yik = a x Dosel3 
where a includes the error. 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Dose proportionality for 
PK parameters will be assessed by restricted maximum likelihood 
using SAS PROC 
MIXED. The mean slope will be estimated from the power model and the corresponding 90% Cl calculated. 
If 
the 90% Cl of the slope of the Cmax and AUCs contains 1, then dose proportionality is indicated. 
Analysis of Variance 
Following log-e transformation, dose-normalized PK parameters will be analyzed with an ANOVA model 
using PROC MIXED. Each dose will be compared with a reference dose on a pairwise basis. The ratio of 
geometric least squares means (LSM) and the corresponding 90% Cl will be estimated for each PK 
parameter of interest. If 
the 90% Cl for the geometric LSM ratio for a given pairwise comparison falls 
completely within the 0.8 to 1.25 equivalence region then dose proportionality is indicated. 
9.5 TFL Layout 
Report layout will be according to the PRA EDS standards, which are International Council for 
Harmonisation (ICH) E3 compliant. The layout of TFLs will be according to the PRA EDS standards. 
TFL shells are provided with and approved as part of this SAP. Small changes to shell layout due to the 
nature of the data may be required after database lock at the discretion of the PRA project statistician. 
Other changes to the shells may be out of scope. The TFLs will be provided both individually in revisable 
text format (RTF) format, with separate files for 
each table, figure, and listing, and combined in Adobe PDF 
format. All TFLs will be in letter 
format. 
10.0 Analysis Populations 
Analyses 
Safety Population 
PK Population 
Disposition Summaries 
 
Baseline Characteristics 
 
 
Safety Assessments 
 
Plasma Concentrations 
 
Plasma PK Parameters 
 
Urine PK Parameters 
 
Dose proportionality Analyses 
 
10.1 Safety Population 
The safety population will include all randomized subjects who received any amount of study drug (ie, a 
partial infusion). Subjects will be analyzed according to the 
treatment received. This population will be used 
for all analyses of accountability, demographics, galidesivir drug concentration, and safety. 
EDSREP 009 T 01 G 
Page 11 of 35 


* PRAHEALTHSCIENCES 
10.2 Pharmacokinetic Population 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DM!D18-0013 
Version Date: 10-April-2019 
The PK population will include all subjects for whom at least 1 PK parameter can be estimated. The PK 
population will be the primary population for the PK analysis. 
11.0 Subject Disposition 
The number and percentage of subjects in each analysis population, who complete as well as withdraw 
from the study prematurely, and a breakdown of the corresponding reasons for withdrawal will be presented 
for the safety population. A listing of screened subjects and reasons for screen failure will also be presented. 
12.0 Protocol Deviations 
Important protocol deviations/violations will be listed as well as included in the CSR. 
13.0 Demographic and Baseline Characteristics 
13.1 Demographics 
Subject demographics will be summarized descriptively for all subjects by cohort. The summary will include 
the subjects' age (in years}, sex, race, ethnicity, weight (kg}, height (cm), and body mass index (BMI) (in 
kg/m2). Demographic characteristics will be summarized for the safety and PK populations. 
All demographic data, as collected during the screening visit, will be listed by subject. 
13.2 Medical History 
Medical history will be categorized by preferred term according to the Medical Dictionary for Regulatory 
Activities (MedDRA) Version 21.1 and will be listed by subject. 
13.3 Screening Results 
All screening results (including eligibility criteria) will be listed by subject. 
14.0 Prior and Concomitant Medications 
Prior and concomitant medications will be categorized by medication group and subgroup according to the 
World Health Organization (WHO) Drug Dictionary Version September 2018 and listed by subject. 
Medications with an end date prior to the first dose of study drug will be considered prior medications and 
will be identified in the listing. Concomitant medications will include records with a start date on the same 
date or after the first study drug administration, and records with a start date before the date of first study 
medication that are indicated as ongoing. If a partial date allows a medication to be considered concomitant 
it will be categorized as such. Records without a start date are assumed to have started before the date of 
first study drug administration. Records without an end date are assumed to be ongoing. 
15.0 Treatment Exposure 
The number of subjects who receive study drug will be summarized by cohort and treatment for the safety 
population. All study drug administration data (including meal data indicating fasting status) will be listed by 
subject. 
Pharmacokinetic Analyses 
EDSREP 009 T 01 G 
Page 12 of 35 


* PRAHEALTHSCIENCES 
16.0 Pharmacokinetic Variables 
16.1.1 Plasma Variables 
• 
Plasma concentrations of galidesivir. 
• 
Plasma PK parameters of galidesivir. 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Venous blood samples will be collected to determine the plasma concentrations of BCX4430. The plasma 
concentration summaries and figures with mean values described in this section will be created using the 
safety population. The plasma PK parameter summaries and statistical analyses described in this section 
will be created using the PK population. 
Plasma PK Parameters 
Parameter 
Description 
j Programming Notes 
AUCt 
% AUCexp 
C1ast 
T1as1 
Cmax 
EDSREP 009 T 01 G 
Area under the concentration versus time curve 
extrapolated to infinite time, calculated as AUC1ast + 
(C1astlAz) 
Area under the concentration versus time curve from time 
zero to time "t"; may be denoted as AUC1ast if the "t" is the 
last timepoint with a measurable concentration 
Percentage of AUC extrapolated between AUC1ast and 
AUC;n1 
Last measurable concentration of drug 
Time of last measurable concentration of drug 
Maximum observed concentration of drug 
AUCINF _obs from WNL 
ff valid fambda_z is not 
present, then parameter is 
flagged in listings and will 
not be used in summary 
statistics. 
AUClast from WinNonlin 
ff actual time deviates 
>20% from nominal time, 
then AUC, will be flagged 
in listings and will not be 
used in statistical 
analyses. If valid Az is not 
present, then AUC, is 
flagged in listings and will 
not be used in statistical 
analyses. 
AUC_%Extrap_obs from 
WinNonlin 
Listed only 
Clast from WinNonlin 
If actual time at T1ast 
deviates >20% from 
nominal time, then 
parameter is flagged in 
listings and will not be 
used in summary statistics. 
Tlast from WinNonlin 
If actual time at T 1as1 
deviates >20% from 
nominal time, then 
parameter is flagged in 
listings and will not be 
used in summary statistics 
Cmax from WinNonlin 
Page 13 of 35 


* PRAHEALTHSCIENCES 
Plasma PK Parameters 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Parameter 
Description 
Programming Notes 
CL 
Az 
Tmax 
Estimate of the terminal elimination half-life of the drug 
CL = Dose/AUG 
where "Dose" is the dose of the drug and AUG = AUCinf 
Terminal elimination rate constant, estimate by linear 
regression of the terminal elimination phase of the 
concentration of drug versus time curve 
Volume of distribution of the drug 
Time to Cmax 
HL_Lambda_z from 
WinNonlin 
If valid llz is not present, 
then parameter is flagged 
in listings and will not be 
used in summary statistics. 
CL_obs from WinNonlin 
Lambda_z from WinNonlin 
If Rsq < 0.80 then 
parameter is flagged in 
listings and will not be 
used in summary statistics. 
Vz_obs from WinNonlin 
If valid llz is not present, 
then parameter is flagged 
in listings and will not be 
used in summary statistics. 
Tmaxfrom WinNonlin 
Note: In all derivations of PK parameters, BQL values at the beginning of the profile will be set to zero, whereas BQL values that 
occur after the first quantifiable point will be considered missing. Samples that are BQL but are between two samples with 
detectable concentrations will be excluded from PK analysis. 
16.1.2 Urine Variables 
• 
Urine concentrations of galidesivir. 
• 
Urine PK parameters of galidesivir. 
Urine samples will be collected to determine the concentrations of galidesivir. The urine PK parameter 
summaries described in this section will be created using the PK population. 
Ct1-t2 
Vt1-t2 
EDSREP 009 T 01 G 
Concentration (of the unchanged drug} in the collection 
interval t1-t2. 
Volume of the urine collected in the interval t1-t2 
Directly from data, no 
calculation required. 
Measured in the 
clinic, captured on 
the CRF, no 
calculation required. 
Page 14 of 35 


* PRAHEALTH S CIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Description 
Amount of drug excreted unchanged into urine in the 
interval t1-t2, calculated as the urine volume times the 
urine concentration for each interval. 
Intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 0-
Aet1-t2 
96h (cumulative) 
Percentage of given dose excreted in the urine as 
unchanged drug 
Intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 0-
% Doseexcreted,11-12 
96h (cumulative) 
Clr 
Renal clearance of unchanged drug cumulatively over all 
collection intervals 
Programming Notes 
Ct1 -t2 *Vt1-t2 
Aet1-t2/Dose*100 
Dose will be 
converted to match 
units of Ae 
Clr=Ae0-t1 /AUC0-t1 
CLr parameter will be 
calculated according 
to time matched AUC. 
Note: Urine PK parameters will be estimated in SAS based on the recorded urine concentrations and volumes. In estimating the 
parameters, all missing values will be recorded as missing and all BLQ values will be set to zero. If a missing value is 
encountered, the cumulative parameters will not be calculated for that subject. 
16.2 Pharmacokinetic Summaries 
16.2.1 Plasma Concentrations 
Plasma concentrations for BCX4430 below the quantifiable limit (BQL) will be set to zero in the computation 
of mean concentration values. Descriptive statistics including n, arithmetic mean, SD, arithmetic CV%, 
geometric mean, geometric CV%, geometric n (the number of subjects with an observation who were 
included in the natural logarithmic transformation) median, min, and max will be used to summarize the 
plasma concentrations by treatment at each scheduled time point. If more than half of the subjects in a 
given cell have values BQL, then the descriptive statistics will not be presented and will instead display as 
BQL for the mean and minimum. Except for n and maximum, all other statistics will be missing. Any value 
less than BQL will be presented as BQL. 
Linear and semi-logarithmic plots of the arithmetic mean and median plasma concentrations by scheduled 
sampling time will be provided by treatment. These plots will show time in hours. The plots will match the 
summary table results and will not have an observation at a given time point if more than half of the subjects 
have values BQL. Mean plots will include SD error bars when plotted on a linear scale and log scale. 
Linear and semi-logarithmic plots of the individual plasma concentrations by actual sampling time will be 
provided by subject (1 subject per page). These plots will show time in hours. Individual plots will use the 
BQL handling procedure described below for "Plasma Pharmacokinetic Parameters". 
All individual subject plasma concentration data will be listed by cohort and treatment. 
16.2.2 Plasma Pharmacokinetic Parameters 
Plasma PK parameters for BCX4430 will be estimated using non-compartmental methods with WinNonlin®. 
The plasma PK parameters will be estimated from the concentration-time profiles. In estimating the PK 
parameters, BQL values at the beginning of the profile will be set to zero. BQL values that occur after the 
first quantifiable point will be considered missing. Samples that are BQL but are between two samples with 
detectable concentrations will be excluded from PK analysis. 
EDSREP 009 T 01 G 
Page 15 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Actual sampling times, rather than scheduled sampling times, will be used in all computations involving 
sampling times. If the actual time or dose time is missing, the scheduled time may be substituted in order 
to calculate the PK parameter. 
Determination of points to be included in Az range will follow the Guideline for Defining, Calculating and 
Summarizing Pharmacokinetic I Pharmacodynamic Parameters (EDSREP 009 R 01) and rule will be noted 
in table and listing footnotes. 
Descriptive statistics (n, arithmetic mean, SD, arithmetic CV%, geometric mean, geometric CV%, median, 
min, and max) will be used to summarize the calculated PK parameters by treatment. For T max, T1a9, and 
T1as1, only n, median, min, and max will be presented. 
Individual PK parameters AUCt, AUCinf, and Cmax with corresponding geometric means will be shown 
graphically for each treatment. 
All individual subject PK parameters will be listed by treatment and period. 
16.2.3 Urine Pharmacokinetic Parameters 
Urine PK parameters will be estimated in SAS based on the recorded urine concentrations and volumes. 
In estimating the parameters, all missing values will be recorded as missing and all BLQ values will be set 
to zero. If a missing value is encountered, the cumulative parameters will not be calculated for that subject. 
Summaries of amounts excreted by treatment and scheduled collection interval (Aet1-t2), including 
cumulative amount excreted, fraction excreted by treatment and scheduled collection interval (% 
Doseexcreted.11-12), 
including cumulative fraction excreted, and renal clearance (Clr) will be provided. 
Descriptive statistics {n, arithmetic mean, SD, arithmetic CV%, geometric mean, geometric CV%, median, 
min, and max) will be used to summarize the calculated PK parameters by treatment. 
16.2.4 Dose Proportionality Analyses 
16.2.4.1 Power Model 
The assessment of dose proportionality for the PK parameters of BCX4430 will use a power model 
approach (including all doses). A model with In-transformed dose (dose continuous) as a fixed effect and 
subject as a random effect will be applied to the following In-transformed PK parameters: AUC1, AUCint, and 
Cmax. Although there is no formal statistical hypothesis tested for this secondary objective, there will be 
evidence for dose-proportionality for each PK parameter if the 90% confidence interval (Cl) of the fixed 
slope for In-dose contains 1. No adjustment for multiplicity will be performed for the set 3 of PK parameters. 
The SAS pseudo code for the power model is as follows: 
data adpp; 
set adpp; 
ln_auc = log(auc); 
ln_dose = log(dose); 
run; 
proc mixed data=adpp method=reml; 
by parameter; 
class subject; 
model ln_auc = ln_dose I ddfm=kr cl alpha=0.1 ; 
random subject; 
run; 
16.2.4.2 ANOVA Model Pairwise Comparisons 
Following log-e transformation, dose-normalized PK parameters will be analyzed with an ANOVA model 
using PROC MIXED. Each dose will be compared with a reference dose on a pair-wise basis. Pairwise 
EDSREP 009 T 01 G 
Page 16 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
comparisons of the ratio of GLS means and the corresponding 90% Cl will be estimated for each PK 
parameter of interest. Although there is no formal statistical hypothesis tested for this secondary objective, 
if the 90% Cl for the geometric LSM ratio falls completely within the 0.8 to 1.25 equivalence region then 
dose proportionality is indicated for the specific comparison. No adjustment for multiplicity will be performed 
for the set of descriptive pairwise comparisons. 
The SAS PROC MIXED pseudo code for the pairwise comparison for the ANOVA model is as follows: 
data adpp; 
set adpp; 
ln_auc_dose = log(auc)/dose; 
run; 
ods output diffs=diffs; 
ods output lsmeans=lsmeans; 
proc mixed data=adpp method=reml; 
by parameter; 
class dose; 
model ln_auc_dose = dose / ddfm=kr; 
lsmeans dose / pdiff alpha=0.1 cl; 
run; 
17.0 Safety Analyses 
The safety summaries described in this section will be created using the safety analysis population. Safety 
analyses will be performed separately for each cohort. 
17 .1 Safety Variables 
The following safety variables will be included: 
• 
Adverse events 
• 
Clinical laboratory evaluations 
o 
Cardiac markers (troponin and creatine kinase-MB [CK-MB]) 
o 
Chemistry 
o 
Coagulation 
o 
Hematology 
o 
Urinalysis 
o 
Serology 
o 
Pregnancy 
o 
Alcohol breath test and urine drug screen 
• 
Vital signs 
o 
Systolic blood pressure 
o 
Diastolic blood pressure 
o 
Pulse rate 
o 
Oral body temperature 
• 
Electrocardiograms 
o 
Heart rate 
o 
RR interval 
o 
PR interval 
o 
ORS duration 
o 
QT interval 
o 
QT interval corrected using Fredericia's method (QTcF) 
• 
Physical examination findings 
EDSREP 009 T 01 G 
Page 17 of 35 


* PRAHEALTHSCIENCES 
17 .1.1 Adverse Events 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition 
in a clinical investigation participant that does not necessarily have a causal relationship with treatment. 
TEAEs are those which occur during or after the administration of the first dose of study drug. All TEAE 
summaries will be presented alphabetically by system organ class, with preferred terms sorted in 
decreasing order of frequency within each system organ class based on MedDRA Version 21.1. 
The following missing data will be imputed (for calculations only} as defined: 
• 
Missing AE start and I or end times for the calculation of onset and duration will be assumed to be 
at 00:01 for a start time and 23:59 for end times 
• 
Missing AE severity or relationship will be assumed to be severe or related, respectively 
• 
Missing AE start times for the determination of treatment emergence will be assumed to occur after 
treatment unless partial date documents the AE as happening prior to treatment 
• 
Missing AE start times for the determination of treatment assignment will be assumed to occur after 
treatment on the recorded date 1 minute after dosing 
• 
Missing AE start date will be assumed to be after treatment for the determination of TEAE but will 
not be attributed to a specific study drug 
A summary of the number and percentage of subjects reporting AEs, TEAEs, serious AEs (SAEs}, and who 
discontinue study drug due to an AE will be provided by cohort and overall for the study. 
A summary of the number and percentage of subjects reporting each TEAE will be provided by cohort and 
treatment, and overall. Counting will be done by subject, not by event; subjects will only be counted once 
within each system organ class or preferred term. 
A summary of the number and percentage of subjects reporting each TEAE will be provided by relationship 
to treatment (BCX4430 formulation, as recorded on eCRF) and by cohort and treatment, and overall. 
Subjects with multiple events will be counted under the category of their most-related event within each 
system organ class or preferred term. 
A summary of the number and percentage of subjects reporting each TEAE will be provided by severity (as 
recorded on eCRF) and by cohort and treatment, and overall within each cohort. Subjects with multiple 
events will be counted under the category of their most severe event within each system organ class or 
preferred term. 
All AEs (including non-treatment-emergent AEs) recorded on the eCRF will be listed by subject. 
A separate listing of AEs leading to study drug discontinuation will be provided by subject. 
17 .1.2 Deaths and Serious Adverse Events 
A listing of deaths and a listing of SAEs will be provided by subject. 
17 .1.3 Laboratory Data 
Clinical laboratory data will be presented using units from the study data tabulation model (SDTM) 
Controlled Terminology. 
A descriptive statistics summary of continuous laboratory results and derived changes from baseline for 
cardiac markers, chemistry, coagulation, hematology, and urinalysis will be provided by cohort and 
scheduled timepoint. 
Laboratory abnormalities outside of the normal laboratory reference ranges and associated grades 
(according to study specific DMID criteria specified in the 2014 DMID Adult Toxicity Grading Scale in 
Appendix 5) should be denoted where possible. For those analyte results that are out of the normal range 
and do not have an established DMID toxicity criteria, the severity grading will be provided by the Pl. The 
number and percentage of subjects experiencing treatment-emergent graded toxicities will be summarized. 
EDSREP 009 T 01 G 
Page 18 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
A shift table describing the change in continuous clinical laboratory values from baseline to follow-up 
(number and percentage of subjects) will also be provided. The following categories will be used: Normal, 
DMID Grade 1, DMID Grade 2, DMID Grade 3, DMID Grade 4. 
All laboratory data will be listed by subject, including laboratory variables not listed in the protocol. 
A separate listing of out-of-range values will also be provided. Normal ranges will be used directly from the 
clinical laboratory and will be included in the listings for reference. Flags for high and low values will be 
provided in the listings. 
17 .1.4 Vital Signs 
A descriptive statistics summary of vital signs and derived changes from baseline will be provided by cohort 
and treatment, and scheduled timepoint. Baseline is defined as measurement prior to initiation of treatment 
on Day 1 of each treatment period, where available. 
All vital signs data will be listed by subject. 
17 .1.5 Electrocardiograms 
A descriptive statistics summary of 12-lead ECG parameters and derived changes from baseline will be 
provided by cohort and treatment, and scheduled timepoint. Where triplicate ECGs are taken, the average 
parameter values of the triplicates will be reported. Baseline is defined as the average of triplicate 
measurements prior to initiation of treatment on Day 1 of each treatment period, where available. 
A summary table for QTcF categories (<=450 msec, >450 to<= 480 msec, >480 to <=500 msec, and > 500 
msec) by cohort and treatment, and timepoint will be presented. The table will also summarize the number 
and percentage of subjects with change from baseline for categories of <= 30 msec, 30 msec to <= 60 
msec, and > 60 msec. 
All 12-lead ECG parameters, physician's conclusions, and corresponding abnormalities and will be listed 
by subject. 
Descriptive statistics will be provided to summarize mean ECG parameters (observed and changes from 
baseline) by treatment, visit, and scheduled time. 
17.1.6 Cardiac Telemetry 
A listing of the cardiac telemetry data will include the start and stop times of telemetric observation, the 
occurrence of any arrythmia or tachycardia of Grade 2 or higher (i.e. heart rate greater than 115 beats per 
minute), and the clinical evaluation of clinical significance of any arrythmia or tachycardia. 
17 .1. 7 Echocardiograms 
A listing of the echocardiogram data will include the date and time of the assessment, the ejection fraction, 
and any clinical finding confirmed by cardiologist. 
17 .1.8 Physical Examination 
All physical examination data will be listed by subject. 
EDSREP 009 T 01 G 
Page 19 of 35 


* PRAHEALTHSC!ENCES 
References 
SAS Institute, Inc., SAS® Version 9.4 software, Cary, NC. 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Clinical Study Protocol. A Phase 1 Drug Interaction Study to Evaluate the Effect of BCX4430 on the 
Pharmacokinetics of Danazol, Amlodipine and Desipramine in Healthy Subjects. Version 1.0, Final, 07 Mar 
2018. 
Gough K, Hutchison M, Keene 0 , Byrom B, Ellis S, Lacey L, McKellar J. (1995). Assessment of dose 
proportionality: Report from the statisticians in the pharmaceutical industry / pharmacokinetics UK joint 
working party, Drug Information Journal, Vol. 29: 1039-1048. 
Patroneva A , Connolly SM, Fatato P, et al. (2008). An assessment of drug-drug interactions: the effect of 
desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy 
subjects. Drug Metab Dispos 36(12): 2484-2491. 
Vincent J , Harris SI, Foulds G , et al. (2000). Lack of effect of grapefruit juice on the pharmacokinetics and 
pharmacodynamics of amlodipine. Br J Clin Pharmacol 50(5): 455-463. 
EDSREP 009 T 01 G 
Page 20 of 35 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 1 0-April-2019 
Appendix 1: Glossary of Abbreviations 
Glossary of Abbreviations: 
AE 
ADaM 
AUC 
AUCint 
AUC1 
AUC%extrap 
BQL 
Cl 
C1ast 
CL/F 
Cmax 
CSR 
CRU 
CV 
DMID 
ECG 
eCRF 
EDS 
LSM 
Max 
MedDRA 
Min 
PK 
QC'd 
SAP 
SAE 
SD 
TEAE 
TFL(s) 
T1ast 
Tmax 
EDSREP 009 T 01 G 
Adverse event 
Analysis data model 
Area under the concentration-time curve 
Area under the concentration versus time curve extrapolated to infinite time 
Area under the concentration time curve from time O to time t (hours) 
Percentage of AUC extrapolated between AUC1 and AUCint. 
Below the quantifiable limit 
Confidence interval 
Concentration observed at the last quantifiable time point. 
Apparent oral clearance after administration of the drug 
Maximum plasma concentration. 
Clinical study report 
Clinical research unit 
Coefficient of variation 
Division of Microbiology and Infectious Disease 
Electrocardiogram 
Electronic case report form 
Early Development Services 
Least squares means 
Maximum 
Medical Dictionary for Regulatory Activities 
Minimum 
Pharmacokinetic 
Quality controlled 
Statistical analysis plan 
Serious adverse event 
Standard deviation 
Treatment-emergent adverse event 
Tables, figures and listings 
Elapsed time from dosing at which analyte was first quantifiable in a 
concentration vs. time profile 
Time of C1as1 
Time of Cmax 
Page 21 of 35 


* PRAHEALTHSCIENCES 
Vz/F 
WHO 
A.z 
EDSREP 009 T 01 G 
Terminal phase half-life expressed in time units 
Apparent volume of distribution of the drug. 
World Health Organization 
Terminal elimination rate constant 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DM!D18-0013 
Version Date: 10-April-2019 
Page 22 of 35 


* 
PRAHEALTHSCIENCES 
Appendix 2: Schedules of Assessments from Protocol 
Schedule of Assessments 
Assessment 
Screening 
In Clinic (CRU) Study Period 
Day-28 
Day-1 
Day I 
Day I 
Day2 
to-2 
(Admission) 
Baseline 
(Post 
(Pre-
dose) 
dose) 
Infonned consent 
X 
Inclusion/exclusion 
X 
X 
criteria 
Medical history 
X 
X 
Weight/height/BMI 
X 
x• 
Drugs of abuse 
X 
X 
screen/urine alcohol 
test/urine cotinine 
screen 
HIV/HCV/HBV 
X 
serology 
Physical 
X 
X 
X 
X 
X 
examinationh 
Concomitant 
X 
X 
X 
X 
X 
medications 
ECG 
xc 
xc 
Xd 
Xd 
Cardiac telemetry 
x• 
x• 
EDSREP 009 T 01 G 
Day3 
Day4 
(Discharge) 
X 
X 
X 
X 
Xd 
Xd 
Page 23 of35 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Return to 
Follow-up or 
CRU for PK 
Early 
Sample 
Termination 
Visit 
Day 5, Day 7, 
Day 21 + 2 
Day 14" 
X 
X 
X 
Xd 


* PRAHEALTHSCIENCES 
Assessment 
Screening 
Day-28 
Day-I 
to-2 
(Admission) 
ECHOr 
xr 
Vital signs 
X 
X 
Pregnancy testh 
X 
X 
FSHi 
X 
Clinical chemistry/ 
X 
xm 
hematology 
Urinalysis 
X 
X'" 
aPTI/PT 
X 
X'" 
Testosteronei 
xm 
Troponin I 
xm 
CK-MB 
xm 
Cystatin C and 
xm 
NGAL 
UACR 
X 
xm 
Plasma for galidesivir 
PK analysisk 
Urine for galidesivir 
PK analysis1 
AE assessment 
X 
Study drug dosing 
EDSREP 009 T 01 G 
In Clinic (CRU) Study Period 
Day 1 
Day 1 
Day2 
Baseline 
(Post 
(Pre-
dose) 
dose) 
xs 
xs 
xs 
X 
X 
X 
Xk 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
Day3 
Day4 
{Discharge) 
xr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 24 of 35 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Return to 
Follow-up or 
CRUforPK 
Early 
Sample 
Termination 
Visit 
Day 5, Day 7, 
Day 21 + 2 
Day 14" 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


* PRAHEALTHSCIENCES 
Statistical Analysis Plan 
BIO139GF-181392 
Protocol: BCX4430-106-DMID18-0013 
Version Date: 10-April-2019 
Abbreviations: AE = adverse event; aPIT = activated partial thromboplastin time; BMI = body mass index; CK-MB = creatine kinase-MB; CRU = clinical 
research unit; ECG = electrocardiogram; ECHO = echocardiogram; FSH = follicle-stimulating honnone; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV 
= human immunodeficiency virus; NGAL = neutrophil gelatinase-associate lipocalin; PK = pharmacokinetic; PT = prothrombin time; UACR = urine 
albumin-to-creatinine ratio. 
a. 
Weight only. 
b. 
A physical examination consisting of the head and neck, skin, chest (lungs and heart), abdomen (gastrointestinal tract, liver, spleen and kidneys), back, 
musculoskeletal system, and neurologic system should be conducted at screening and on Day 4 prior to discharge. Breast and genitourinary system do not 
require examination unless the potential subject indicates a complaint or comorbidity that could result in exclusion. All other physical exams will be 
symptom directed. The site of infusion should be checked for any changes in skin. 
c. 
Three (3) serial ECGs will be performed at screening and baseline 1- 3 minutes apart. Pre-dose ECG should be collected within ~ 2 hours of the first dose. 
d. 
12-lead ECGs will be conducted on Day 1 at 2 and 4 hours post dose (post start of the infusion) and on Day 2 at 24 hours post dose. An acceptable window 
is ± 10 minutes from the nominal time point. All subsequent ECGs are daily. 
e. 
Cardiac telemetry will be initiated 2: 2 hours prior to administration of the dose and will continue for 24 hours after the infusion is started. Subjects may be 
disconnected for bathroom, hygiene needs, and for 20-minute periods 3 times a day for meals. In addition, subjects may be disconnected for IO minutes 
every 2 hours while awake for mild physical exercise such as walking or calf exercises. 
f. 
The ECHO may be performed at any time from screening to Day -1 for eligibility determination. An ECHO should also be performed on Day 3. An 
acceptable window for the Day 3 ECHO is up until Day 4 discharge. 
g. 
Vital signs ( except temperature) will be obtained pre-dose (within 2 hours of dosing) 1, 2, 4, and 8 hours post dose (post start of the infusion) on Day 1, at 
24 hours post dose on Day 2 and once per day where indicated. Oral temperature will be obtained at 8 hours post dose on Day I and at 24 hours post dose 
on Day 2. Subjects should be rested for IO minutes in the supine position prior to vital sign measurements. 
h. 
A serum pregnancy test will be administered at screening to all women; all other pregnancy tests performed during the study may be urine pregnancy tests. 
i. 
An FSH level will be measured in women who report that they have been postmenopausal ~ 2 years. 
j. 
Free testosterone will be measured in male subjects. 
k. 
Plasma for PK galidesivir analysis will be collected pre-dose, 30 min (halfway through the infusion), l h (end of the infusion), 1.25 h, 1.5 h, 2 h, 3 h, 4 h, 6 
h, 8 h, 10 h, 12 h,16 h, 24 h, 36 h, 48 h, 60 h, 72 h, and 96 h following the start of the infusion. The pre-dose PK sample must be collected within ~ 1 hour 
of the dose. Assessment windows around each PK draw will be ± 2 minutes for sampling times up to 2-hour post dose and from 2-hour post dose onward, 
± 10 minutes while subject is confined in the unit. All sample times are from the start of the infusion. 
I. 
For the analysis of urinary excretion of galidesivir, an aliquot of urine will be collected pre-dose (0 hour) and all urine will be collected for the following 
post dose intervals: 0- 12 hours, 12-24 hours, 24-48 hours, 48-72 hours, and 72-96 hours. All sample times are from the start of the infusion. 
m. 
Baseline for study post dose comparisons. NGAL, cystatin C, UACR, testosterone, troponin I, and CK-MB can be collected on Day -1 or Day I (pre-dose). 
n. 
Subjects will return to the CRU to have a plasma PK sample collected on Day 5 (+ l), Day 7 (+l), and Day 14 (± 1). This visit is intended to be a short visit 
(approximately 1-2 hours) and can take place at any time during the specified window. A plasma PK sample will also be collected at the follow-up visit on 
Day 21. 
EDSREP 009 T 01 G 
Page 25 of 35 


Appendix 3: List of End of Text Outputs 
List of End of Text Tables and Figures: 
Output 
Title 
Analysis 
Section 14. 1 - Disposition and Demographic Data 
Table 14.1.1 
Table 14.1.2.1 
Table 14.1.2.2 
Table 14.1.3 
Summary of Subject Disposition 
Summary of Demographics 
Summary of Demographics 
Summary of Study Drug Administration 
Section 14.2- Plasma Pharmacokinetic Data 
Table 14.2.1 
Table 14.2.2 
Table 14.2.3 
Table 14.2.3.1 
Table 14.2.3.2 
Figure 14.2.4 
Figure 14.2.5 
Figure 14.2.6 
Figure 14.2.7 
Figure 14.2.8 
Figure 14.2.9 
Summary of BCX4430 Plasma Concentrations 
Summary of BCX4430 Plasma Pharmacokinetic Parameters 
Summary of BCX4430 Urine Pharmacokinetic Parameters 
Statistical Analysis of the Dose Proportionality: Power Model 
Statistical Analysis of the Dose Proportionality: ANOVA Model of 
Pairwise Comparisons 
Plot of Mean (±SD) BCX4430 Plasma Concentrations vs Time on a 
Linear Scale 
Plot of Mean BCX4430 Plasma Concentrations vs Time on a Semi-Log 
Scale 
Plot of Median BCX4430 Plasma Concentrations vs Time on a Linear 
Scale 
Plot of Individual BCX4430 Plasma Concentrations vs Time on a Linear 
Scale 
Plot of Individual BCX4430 Plasma Concentrations vs Time on a Semi-
Log Scale 
Scatter Plot of Individual BCX4430 Plasma Pharmacokinetic Parameters 
Section 14.3- Safety Data 
Table 14.3.1.1 
Table 14.3.1 .2 
Table 14.3.1 .3 
Table 14.3.1.4 
Table 14.3.2 
Table 14.3.3 
Table 14.3.4 
Table 14.3.5.1 
Table 14.3.5.2 
EDSREP 009 T 01 G 
Summary of Adverse Events 
Summary of Treatment Emergent Adverse Events by System Organ 
Class and Preferred Term 
Summary of Treatment Emergent Adverse Events by Relationship to 
BCX4430 
Summary of Treatment Emergent Adverse Events by Severity 
Listing of Serious Adverse Events 
Listing of Deaths 
Listing of Abnormal Laboratory Values 
Summary of Laboratory Results 
Summary of Laboratory Shifts from Baseline 
Population 
All Subjects 
Safety 
PK 
Safety 
Safety 
PK 
PK 
PK 
PK 
Safety 
Safety 
Safety 
Safety 
Safety 
PK 
Safety 
Safety 
Safety 
Safety 
All Subjects 
All Subjects 
All Subjects 
Safety 
Safety 
Page 26 of 35 


Table 14.3.5.3 
Table 14.3.6 
Table 14.3.7.1 
Table 14.3.7.2 
Summary ofTreatment Emergent Graded Laboratory Toxicities 
Summary of Vital Signs 
Summary of 12-Lead Electrocardiogram Results 
Summary of QTcF Categorical Findings 
List of End of Text Listings: 
Output 
Title 
Section 16.2.1- Disposition 
Listing 16.2.1.1 
Subject Disposition 
Listing 16.2.1.2 
Eligibility Criteria 
Section 16.2.2- Protocol Deviations 
Listing 16.2.2 
Important Protocol Deviations 
Section 16.2.3- Excluded Subjects 
Listing 16.2.3 
Analysis Populations 
Section 16.2.4- Demographics and Baseline Characteristics 
Listing 16.2.4.1 
Listing 16.2.4.2 
Listing 16.2.4.3 
Subject Demographics 
Medical History 
Prior and Concomitant Medications 
Section 16.2.5- Compliance 
Listing 16.2.5.1 
Study Drug Administration 
Listing 16.2.5.2 
Meal Administration 
Section 16.2.6- Response Data 
Listing 16.2.6.1 
Plasma Concentrations 
Listing 16.2.6.2 
Plasma Pharmacokinetic Parameters 
Listing 16.2.6.3 
Urine Pharmacokinetic Parameters 
Section 16. 2. 7 - Adverse Events Data 
Listing 16.2. 7.1 
Adverse Events 
Listing 16.2.7.2 
Adverse Events Leading to Study Drug Discontinuation 
Section 16.2.8- Laboratory Data 
Listing 16.2.8.1 
Listing 16.2.8.2 
Listing 16.2.8.3 
Listing 16.2.8.4 
Listing 16.2.8.5 
Listing 16.2.8.6 
Clinical Laboratory Results - Cardiac Markers 
Clinical Laboratory Results - Chemistry 
Clinical Laboratory Results - Coagulation 
Clinical Laboratory Results - Hematology 
Clinical Laboratory Results - Urinalysis 
Clinical Laboratory Results - Serology 
Listing 16.2.8.7 
Clinical Laboratory Results - Pregnancy and FSH 
Listing 16.2.8.8 
Clinical Laboratory Results - Urine Drug and Alcohol Screen 
Section 16.2.9-10- Other Safety Data 
EDSREP 009 T 01 G 
Safety 
Safety 
Safety 
Safety 
Page 27 of 35 


Listing 16.2.9 
Vital Signs 
Listing 16.2.10 
12-Lead Electrocardiogram Results 
Listing 16.2.11 
Cardiac Telemetry Results 
Listing 16.2.12 
Echocardiogram Results 
Listing 16.2.13 
Physical Examination Findings 
Other Appendix Outputs: 
Output 
Title 
Appendix 16.1.9.2 
Statistical Appendices 
EDSREP 009 T 01 G 
Page 28 of 35 


Appendix 4: Shells for Post-Text Tables, Figures and Listings 
Shells are provided in a separate document. 
Appendix 5: Toxicity Table - Modified DMID Adult toxicity Table, 2014 
Clinical Adverse 
Events 
VITAL SIGNS 
Mild 
Moderate (Grade 2) 
Severe 
(Grade 1) 
(Grade 3) 
Fever (°C) ** 
38.0 - 38.4 
38.5-38.9 
<!39.0 
(OF) ** 
100.4-101.1 
101.2-102.0 
>102.0 
** Oral temperature; no recent hot or cold beverages or smoking. A protocol should select 
either 
0c or °F for inclusion. 
Tachycardia - beats 
101-115 
116 - 130 
> 130 or ventricular 
per minute 
dysrhythmias 
Bradycardia - beats 
50 - 54 or 45-50 
45 - 49 or 40-44 if 
< 45 or <40bpm if 
per minute 
bpm if baseline <60 
baseline <60bpm 
baseline <60bpm 
bpm 
Hypertension# 
141-150 
151-160 
> 160 
(systolic)- mm Hg 
Hypertension# 
91-95 
96-100 
> 100 
(diastolic) - mm Hg 
# Assuming supine position, 10 min at rest conditions, not sleeping subjects, measurements on 
the same arm and several concordant results. 
EDSREP 009 T 01 G 
Page 29 of 35 


Hypotension 
85-89 
80-84 
< 80 
(systolic) - mm Hg 
Tachypnea-
23-25 
26-30 
>30 
breaths per minute 
CARDIOVASCULA 
Grade 1 
Grade 2 
Grade 3 
R 
Arrhythmia 
asymptomatic, 
recurrenVpersistent; 
transient signs, no Rx 
symptomatic Rx 
required 
required 
QTcF interval 
Asymptomatic, QTcF 
Asymptomatic, QTcF 
Asymptomatic, QTcF 
prolonged (msec) 
>450-480 msec 
>500 msec OR 
>480-500 msec OR 
increase in interval 
increase in interval 30-
>60 msec from 
60 msec from baseline 
baseline 
Hemorrhage, Blood 
Estimated blood 
Estimated blood loss > 
Transfusion required 
Loss 
loss ~100 ml 
100 ml, no transfusion 
required 
RE SPIRA TORY 
Grade 1 
Grade 2 
Grade 3 
Cough 
Transient- no 
Persistent cough; 
Interferes with daily 
treatment 
activities 
Bronchospasm, 
transient; no 
requires treatment; 
no normalization with 
Acute 
treatment; 71 % -
normalizes with 
bronchodilator; FEV1 
80% FEV1 of peak 
bronchodilator; FEV1 
<60% of peak flow 
flow 
60% - 70% ( of peak 
flow) 
Dyspnea 
Does not interfere 
Interferes with usual 
Prevents daily and 
with usual and social 
and social activities, no 
usual social activity 
activities 
treatment 
or requires treatment 
GASTROINTESTIN 
Grade 1 
Grade 2 
Grade 3 
AL 
Nausea 
No interference with 
Some interference with 
Prevents daily 
activity 
activity 
activities 
Vomiting 
No interference with 
Some interference with 
Prevents daily activity 
activity or 1 - 2 
activity or > 2 
or requires IV 
episodes/24 hours 
episodes/24 hours 
hydration 
EDSREP 009 T 01 G 
Page 30 of 35 


Diarrhea 
2 - 3 loose or watery 
4 - 5 loose or watery 
6 or more loose or 
stools or < 400 
stools or 400 - 800 
watery stools or > 
gms/24 hours 
gms/24 hours 
800gms/24 hours or 
requires IV hydration 
SYSTEMIC 
Mild 
Moderate 
Severe 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Allergic 
pruritus without rash 
localized urticaria 
generalized urticaria; 
Reaction/Hypersens 
angioedema or 
itivitv 
anaphylaxis 
Headache 
No interference with 
Repeated use of non-
Significant; any use 
activity 
narcotic pain reliever > 
of narcotic pain 
24 hours or some 
reliever or prevents 
interference with 
daily activity 
activity 
Fatigue 
No interference with 
Some interference with 
Significant; prevents 
activity 
activity 
daily activity 
Myalgia 
No interference with 
Some interference with 
Significant; prevents 
activity 
activity 
daily activity 
All Other 
Mild 
Moderate (Grade 2) 
Severe 
conditions 
(Grade 1) 
(Grade 3) 
Illness or clinical 
Transient or mild 
Symptom results in 
Symptom results in 
adverse event (as 
symptoms; no 
mild to moderate 
significant limitation 
defined according to 
limitation in activity; 
limitation in activity; no 
in activity; medical 
applicable 
no intervention 
or minimal intervention 
intervention may be 
regulations) 
required. The AE 
required. The AE 
required. The AE 
does not interfere 
produces some 
produces significant 
with the participant's 
impairment of 
impairment of 
normal functioning 
functioning, but it is not 
functioning or 
level. It may be an 
hazardous to health. It 
incapacitation. 
annoyance. 
is uncomfortable or an 
embarrassment. 
EDSREP 009 T 01 G 
Page 31 of 35 


Laboratory Adverse 
Events 
Blood, Serum, or Plasma 
Reference Range ** 
Mild 
Moderate 
Severe 
* 
(Grade 1) 
(Grade 2) 
(Grade 3) 
Sodium - Hyponatremia 
135-146 mmol/L 
134 - <LLN 
132 -133 
<132 
mEq/L 
Sodium - Hypernatremia 
135-146 mmol/L 
>ULN -147 
148 - 149 
>149 
mEq/L 
Potassium - Hyperkalemia 
3.5-5.3 mmol/L 
>ULN-5.4 
5.5 -5.6 
>5.6 
mEq/L 
Potassium - Hypokalemia 
3.5-5.3 mmol/L 
<LLN-3.4 
<3.4- 3.3 
<3.3 
mEq/L 
Glucose - Hypoglycemia 
65-99 mg/dl 
62 - 64 
52-62 
<52 
mQ/dL 
Glucose - Hyperglycemia 
65-99 mg/dl 
>ULN - 100 
101-110 
>110 
Fastina - ma/dl 
Glucose - Hyperglycemia 
65-139 mg/dl 
140 -159 
160-200 
>200 
Random - mQ/dL 
Blood Urea Nitrogen mg/dl 
7-25 mg/dl 
26-29 
30-34 
>34 
Creatinine (Male) - mg/dl 
18Y-19Y 
0.60-1 .26 
>ULN -1.36 
>1.36-1.56 
>1 .56 
mg/dl 
20Y-49Y 
0.60-1.35 
>ULN -1.45 
>1.45- 1.65 
>1.65 
mg/dl 
50Y-59Y 
0.70-1.33 
>ULN -1.43 
>1.43 - 1.63 
>1.63 
mQ/dL 
Creatinine (Female)- mg/dl 18Y-19Y 
0.50-1.00 
>ULN-1.10 
>1.10 - 1.30 
>1 .30 
mg/dl 
20Y-49Y 
0.50-1.10 
>ULN-1.20 
>1.20 - 1.40 
>1.40 
mg/dl 
50Y-59Y 
0.50-1.05 
>ULN-1.15 
>1.15- 1.35 
>1.35 
mq/dl 
Calcium - hypocalcemia 
18Y-19Y 
8.9-10.4 
8.8-<LLN 
8.3- 8.7 
<8.3 
mg/dl (Male} 
mg/dl 
20Y-133Y 
8.6-10.3 
8.5-<LLN 
8.0- 8.4 
<8.0 
mg/dl 
Calcium - hypocalcemia 
18Y-19Y 
8.9-10.4 
8.8 - <LLN 
8.3-8.7 
<8.3 
mg/dl (Female) 
mg/dl 
20Y-49Y 
8.6-10.2 
8.5- <LLN 
8.0 - 8.4 
<8.0 
mg/dl 
50Y-133Y 
8.6-10.4 
ma/dL 
8.5-<LLN 
8.0- 8.4 
<8.0 
Calcium - hypercalcemia 
18Y-19Y 
8.9-10.4 
>ULN-10.5 
10.6-11.0 
>11.0 
mg/dl (Male) 
mg/dl 
20Y-133Y 
8.6-10.3 
>ULN -10.4 
10.5 -10.9 
>10.9 
mq/dl 
Calcium - hypercalcemia 
18Y-19Y 
8.9-10.4 
>ULN-10.5 
10.6 -10.9 
>10.9 
mg/dl (Female) 
mg/dl 
20Y-49Y 
8.6-10.2 
>ULN-10.3 
10.4-10.7 
>10.7 
mg/dl 
50Y-133Y 
8.6-10.4 
>ULN-10.5 
10.6-10.9 
>10.9 
mg/dl 
EDSREP 009 T 01 G 
Page 32 of 35 


Magnesium -
1.5-2.5 mg/dl 
1.3-1.5 
1.1 - 1.2 
<1.1 
hvoomaanesemia mg/dl 
Phosphorous -
18Y-64Y 
2.5-4.5 
2.3- <2.5 
2.0-< 2.2 
<2.0 
hypophosphatemia mg/dl 
mg/dl 
65Y-133Y 
2.1-4.3 
1.9 - <2.1 
1.6- < 1.8 
<1.6 
ma/dl 
CPK - U/L (male) 
<196 
196 - 1000 
1001-1500 
>1500 
CPK - U/L (female} 
<143 
143-1000 
1001-1500 
>1500 
Albumin-
3.6-5.1 g/dl 
3.0- 3.5 
2.7 -2.9 
<2.7 
Hypoalbuminemia g/dl 
Total Protein -
18Y-19Y 
6.3-8.2 g/dl 
6.1 -6.3 
5.7 -6.0 
<5.7 
Hvpooroteinemia g/dl 
20Y-133Y 
6.1-8.1 g/dl 
5.9-6.1 
5.5- 5.8 
<5.5 
Alkaline phosphatase - U/L 
18Y-19Y 
48-230 U/L 
230-340 
341 -460 
>460 
(Male) 
20Y-133Y 
40-115 U/L 
115 -225 
226 - 345 
>345 
Alkaline phosphatase - U/L 
18Y-19Y 
47-176 U/L 
176 - 286 
287-406 
>406 
(Female) 
20Y-49Y 
33-115 U/L 
115-225 
226- 345 
>345 
50Y-133Y 
33-130 U/L 
130-240 
241 -360 
>360 
AST (Male) U/L 
18Y-19Y 
12-32 U/L 
32-93 
94-163 
>163 
20Y-49Y 
10-40 U/L 
40 - 101 
102 -171 
>171 
50Y-133Y 
10-35 U/L 
35-96 
97 - 166 
>166 
AST (Female) U/L 
18Y-19Y 
12-32 U/L 
32 - 93 
94-163 
>163 
20Y-44Y 
10-30 U/L 
30 - 91 
92-161 
>161 
45Y-133Y 
10-35 U/L 
35-96 
97-166 
>166 
ALT (Male) U/L 
18Y-19Y 
8-46 U/L 
46 - 101 
102 -171 
>171 
20Y-133Y 
9-46 U/L 
46 - 101 
102 -171 
>171 
ALT (Female) U/L 
18Y-19Y 
5-32 U/L 
32 - 87 
88- 157 
>157 
20Y-133Y 
6-29 U/L 
29-84 
85-154 
>154 
Bilirubin (serum total) 
18Y-19Y 
0.2-1.1 
1.2 -1 .9 
2.0 - 2.4 
>2.4 
mg/dL 
mg/dl 
20Y-133Y 
0.2-1 .2 
1.3-2.0 
2.1- 2.5 
>2.5 
ma/dL 
Bilirubin - when ALT ~105 
1.3 - 1.5 
1.6 - 2.0 
>2.0 
(Hy's law) 
Amylase- U/L 
21 - 101 U/L 
102 - 177 
178-278 
>278 
Lipase- U/L 
7-60 U/L 
60-165 
166-250 
>250 
Hemoglobin (Male) - g/dL 
18Y 
12.0-16.9 
11.5 - 12.0 
10.5 - 11.9 
<10.5 
g/dL 
19Y-133Y 
13.2-17.1 
12.7 -13.2 
12.2-12.7 
<12.2 
a/dL 
Hemoglobin (Female) -
18Y 
11.5-15.3 
11.0-11 .5 
9.5-10.9 
<9.5 
g/dl 
g/dL 
19Y-133Y 
11.7-15.5 
11.2 -11 .7 
9.8-11 .2 
<9.8 
a/dL 
WBC Increase - cell/mm3 
18Y 
4,500-
13,001 -
17,001 -
>22,000 
13,000/uL 
17,000 
22,000 
19Y-133Y 
3,800-
10,801 -
14,801 -
>19,800 
10 800/uL 
14 800 
19,800 
WBC Decrease - cell/mm3 
18Y 
4,500-
3,500-
2,500-
<2,500 
13,000/uL 
4,500 
3,499 
19Y-133Y 
3,800-
2,800 -
1,800-
<1,800 
10 800/uL 
3,800 
2,799 
EDSREP 009 T 01 G 
Page 33 of 35 


Lymphocytes Decrease -
18Y 
1200-5200 
950-1 ,200 
700- 949 
<700 
cell/mm3 
cells/ul 
19Y-133Y 
850-3900 
600-850 
450 -599 
<450 
cells/ul 
Neutrophils Decrease -
18Y 
1800-8000 
1,300-
1,049-
<1,049 
cell/mm3 
cells/ul 
1,799 
1,299 
19Y-133Y 
1500-7800 
1,000-
750 - 999 
<750 
cells/ul 
1499 
Eosinophils - cell/mm3 
15-500 cells/ul 
500- 750 
751 -1600 
>1600 
Platelets Decreased -
140,000 - 400,000/ ul 
130,000 -
110,000-
<110,000 
cell/mm3 
140,000 
129,999 
PT - seconds (prothrombin 
9.0-11.5 seconds 
> ULN-14.4 
14.5 -15.7 
>15.7 
time) 
PTT - seconds (partial 
22-34 sec 
>ULN-34.1 
34.2-42.0 
>42.0 
thromboplastin time) 
Fibrinogen increase -
175-425 mg/dl 
>ULN-425 
426 - 525 
>525 
mo/dl 
Fibrinogen decrease -
175-425 mg/dl 
<LLN - 175 
160 -174 
<160 
mg/dl 
Urine* 
Mild 
Moderate 
Severe (Grade 3) 
(Grade 1) 
(Grade 2) 
Protein 
1+ 
2+ 
>2+ 
Glucose 
1+ 
2+ 
>2+ 
Blood (microscopic) - red 
5-10 
11-50 
> 50 and/or gross 
blood cells per high power 
blood 
field (rbc/hpf) 
* The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. 
* Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
** Reference ranges are from Quest Diagnostics. Any age range that is not specified is 18Y 
-133Y 
EDSREP 009 T 01 G 
Page 34 of 35 


Document History 
Version Date 
I Modified/Reviewed By 
J Brief Summary of Changes 
21-Jan-2018 
28-Mar-2018 
EDSREP 009 T 01 G 
Jacqueline Cater 
Stephannie Kollipara 
Emily Mick 
Jacqueline Cater 
Emily Mick 
Created from EDSREP 009 T 01 G. 
Revised according to sponsor comments (using updated 
protocol and eCRF). 
Page 35 of 35 


P RAH EALTHS CIE NC ES 
Dose Escalation Report 
BioCryst BCX4430-106 
Version Date: 07 Jan2019 
A PHASE 1 DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY 
TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF 
GALIDESIVIR (BCX4430) ADMINISTERED AS SINGLE DOSES VIA INTRAVENOUS 
INFUSION IN HEAL THY SUBJECTS 
For BioCryst: 
DMID: 
For PRA: 
Protocol#: BCX4430-106 / DMID 18-0013 
PRA Study Code: 181392 
Dose Escalation Report 
Single Ascending Dose 
Cohort 1: 5 mg/kg 
Report Date:· 07 Jan2019 
Bill Sheridan, MB, BS, Medical Monitor/ Chief Medical Officer 
Amanda Mathis, PhD, Clinical Pharmacologist 
Venus S. Shahamatdar, MD, Medical Monitor 
Kay M. Tomashek, MD, MPH, DTM, Medical Officer 
Carol Ostrye, RN, MPH, Clinical Project Manager 
Daniel Dickerson, MD, PhD, Principal Investigator 
Jamie Easum, APRN-BC, Co-Lead Sub-Investigator 
Lesa Davis, PA-C, Co-Lead Sub-Investigator 
Traci Goodwin, Clinical Study Manager 
Tim Theisen, Project Manager 
Safety Assessment Following Dose Administration of BCX4430 or Placebo to Healthy Volunteers 
EDSEXE 013 T 01 C 
Page 1 of 2 
Note: The above information serves to document the review of safely information for the referenced study, The information 
contained in or appended to this report is not considered a source document and has not been subjected lo definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved, 


. PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
Version Date: 07Jan2019 
1.Q Subject Demographics, Dosing Date and Administration Times (All subjects 
dosed under fed conditions). 
2.0 Adverse Events 
2.1 Adverse Event Comments (summarize findings from above table): 
3.0 Safety Lab Data: (Summary of significant or notable lab results) 
EDSEXE 013 T 01 C 
Page 1 of 3 
Note: The above information serves to document the review of safety information for the referenced study. The information 
contained in or appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
11006 
01-014 
M 
45 
13Dec2018 
Phosphate 
2.1 
mg/dl 
11006 
01-014 
M 
45 
14Dec2018 
Phosphate 
2,4 
mg/dl 
11006 
01-014 
M 
45 
15Dec2018 
Glucose 
148 
mg/dl 
11006 
01-014 
M 
45 
15Dec2018 
Phosphate 
2.4 
mg/dl 
1'l00'7 
~2 
14Qe9?0l~ 
Plu~o.ie 
62mgidL 
'\"• 
• 
h'/• 
11.007 
$2 
02J_an201.9 
,¥1.ehlqglobfri 
; '1~;.6,9{fJL , " 
HP07 
~2 , :02~.~n201\l 
,, ~\,, ,,, ,.,,,', ,/. "'· 
~.P~ 
1i39',l;J/t;.:.· 
110()8 
PH>2S 
(52 
P2.J.an2.01 a 
ALT 
32U/L 
11008 
:01.023 
F 
62 
02Jan2018 
Amylase 
105U/L 
*N.B. Subject 11004 had elevated CPK at screening and on Day -1. 
3.1 Actions Taken/Con Meds Administered Related to Adverse 
EDSEXE 013 T 01 C 
Dose Escalation Report 
BioCryst BCX4430-106 
2.5-4.5 mg/dl 
2 
2.5-4.5 mg/dl 
1 
65-139 mg/dl 
1 
2.5-4.5 mg/dl 
1 
;~5fW91Jng/dL., 
1 
1 
.1 
6-29 U/L 
1 
2M01/L 
1 
Events: 
Page 1 of 4 
Note: The above information serves to document the review of safety information for the referenced study. The information 
contained in or appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences, All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
Version Date: 07 Jan2019 
4.0 Vital Signs Data (summary of clinically significant abnormal vital signs by 
subject# and time point taken): 
*There were no vital signs which met the criteria for halting dosing in Section 11.5.2 of the protocol 
5.0 12-Lead ECG Data (summarize clinically significant abnormal changes by 
subject# and time point taken): There were no clinically significant ECG findings, and no ECG 
parameters met the criteria for halting dosing stated in Section 11.5.2 of the protocol. 
6.0 Physical Examination Data (summarize clinically significant abnormal 
changes by subject# and tinae point perfonned); There were no clinically significant 
physical exam findings noted, 
7.0 Subject Discontinuations: No subjects were discontinued. 
8.0 PK Summary (insert tables, appendices as allowed by sponsor, if available): 
Subjects in the table below have been anonymized with an alphabet code. Samples collected through 96 
hours post-dose were shipped for analysis, and therefore AUCo-tast in the table below represents 96 hours. 
Samples were quantifiable through 96 hours in all subjects. The geometric mean(%CV) Cmax, AUCo-24 
and AUC0-1ast were 5540 ng/ml (8), 10850 ng.h/ml (11 ), and 14530 ng.h/ml (12), respectively. 
No PK parameters met halting rules, and overall, the PK following a 5 mg/kg single dose administered by 
IV infusion was in line with anticipated exposure based on modeling and simulation. 
A 
96.9 
5420 
10000 
13660 
19440 
30 
257 
B 
55.9 
4870 
11270 
15190 
18110 
16 
276 
C 
191.6 
6140 
11040 
14390 
24760 
42 
202 
D 
75.3 
5510 
10460 
13730 
17110 
20 
292 
E 
170.6 
5590 
12910 
17830 
31410 
43 
159 
F 
92.9 
5820 
9700 
12860 
17320 
26 
289 
Geomean 
103,6 
5540 
10850 
14530 
20810 
28 
240 
%CV 
50.2 
8 
11 
12 
27 
38 
22 
*the timepoint for Cmax was taken at the end of the 1-hour infusion 
EDSEXE 013 T 01 C 
Page 1 of 5 
Note: The above information serves to document the review of safety information for the referenced study, The information 
contained in or appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 
35960 
22270 
55830 
· 31760 
39180 
38680 
35930 
30 


PRAH EALTH SCI ENCE S 
10000 
-
..J 
E -
en 1000 
C -
a.. 
:~ 
UJ 
Cl) 
100 
II I 
:2 
• I • 
i 
cu 
(!) 
10 
0 
50 
time (h) 
• 
II 
A. 
'f 
 
• 
I 
• • 
I 
100 
A 
B 
C 
D 
E 
F 
Dose Escalation Report 
BioCryst BCX4430-106 
Version Date: 07Jan2019 
9.0 Investigator opinion about safety of IP based upon clinical tolerance of trial 
during reported period: 
Internal review of a
l
l available safety data prior to the dose escalation call shows no concerns w
ith 
proceeding to the next dose leve
l. 
10.0 Summary of Discussion at Dose Escalation Call: 
Subject 11004 had a grade 2 elevated CPK at her end of study laboratory evaluation. The subject had no 
physical symptoms associated w
ith this elevated CPK and on review of her previous labs, she had 
elevated CPK at screening and on Day -1. She is scheduled to have her CPK redrawn today, 07 Jan2019. 
The safety committee had no concerns regarding this laboratory excursion. 
Subjects 1105 and 1106 had grade 2 decreases in phosphate which rapidly corrected. Neither subject 
had signs or symptoms of hypophosphatemia. The safety committee had no concerns regarding these 
lab excursions. We will continue monitoring for trends. 
Based upon safety measures, tolerance, and pharmacokinetic results, the dose of 5 mg/kg was well 
tolerated. The Safety Committee discussed data and agreed that data supports moving forward w
ith 
dose escalation without changes to the protocol. 
EDSEXE 013 T 01 C 
Page 1 of6 
Note: The above information serves to document the review of safely information for the referenced study. The information 
contained in or appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved, 


PRAHEALTHSCIENCE S 
Current Dose Level: 5 mg/kg 
Next Dose Level: 
10 mg/kg 
Dose Escalation Report 
BioCryst BCX4430-106 
Version Date: 07 Jan2019 
Protocol changes required prior to next dose level administration (e.g. additional 
safety monitoring)? 
Yes 
D 
No 
l2'J 
Daniel Dickerson, MD, PhD 
Principal Investigator 
PRA EDS-Lenexa 
.. ,)-iuw, ~ r~ M,l) ()hr\ 
fix 'B'i \ I She.-v{ cl Q,/f' 
Bill Sheridan, MB, BS 
Medical Monitor 
BioCryst Chief Medical Officer 
Amanda Mathis 
Director, Clinical Pharmacology 
BioCryst Pharmaceuticals 
EDSEXE 013 T 01 C 
Date 
Date 
Date 
Page 1 of6 
Note: The above information serves to document the review of safety information for the referenced study. The information 
contained in or appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
A PHASE 1 DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF GALIDESIVIR 
(BCX4430) ADMINISTERED AS SINGLE DOSES VIA INTRAVENOUS INFUSION IN 
HEAL THY SUBJECTS 
For BioCryst: 
DMID: 
For PRA: 
Protocol #: BCX4430-106 / DMID 18-0013 
PRA Study Code: 181392 
Dose Escalation Report 
Single Ascending Dose 
Cohort 2: 10 mg/kg 
Report Date: 01 Feb2019 
Diane Gesty-Palmer MD, PhD, Medical Monitor/Senior Medical Director 
Amanda Mathis, PhD, Clinical Pharmacologist 
Venus S. Shahamatdar, MD, Medical Monitor 
Kay M. Tomashek, MD, MPH, DTM, Medical Officer 
Carol Ostrye, RN, MPH, Clinical Project Manager 
Daniel Dickerson, MD, PhD, Principal Investigator 
Jamie Easum, APRN-BC, Co-Lead Sub-Investigator 
Lesa Davis, PA-C, Co-Lead Sub-Investigator 
Traci Goodwin, Clinical Study Manager 
Tim Theisen, Project Manager 
Safety Assessment Following Dose Administration of BCX4430 or Placebo to Healthy Volunteers 
EDSEXE 013 T 01 C 
Page 1 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
1.0 Subject Demographics, Dosing Date and Administration Times (All subjects dosed 
under fed conditions). 
2.0 Adverse Events 
2.1 Adverse Event Comments (summarize findings from above table): 
EDSEXE 013 T 01 C 
Page 2 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected lo definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
3.0 Safety Lab Data: (Summary of significant or notable lab results) 
EDSEXE 013 T 01 C 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
Page 3 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
3.1 Actions Taken/Con Meds Administered Related to Adverse Events: 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
4.0 Vital Signs Data (summary of clinically significant abnormal vital signs by subject# 
and time point taken): 
12002 
12002 
01-044 
01-044 
M 
M 
26 
26 
09Jan2019 
1305 
10Jan2019 
091 0 
:~~xtaJues"~' 
. 
~ 
"' 
J:.,a 
54bpm 
54bpm 
1 
1 
5.0 12-Lead ECG Data (summarize clinically significant abnormal changes by subject# 
and time point taken): There were no clinically significant ECG findings, and no ECG parameters met the 
criteria for halting the infusion stated in Section 7.6.3.2 of the protocol. 
6.0 Physical Examination Data (summarize clinically significant abnormal changes by 
subject# and time point performed): There were no clinically significant physical exam findings noted. 
7.0 Subject Discontinuations: There were no subject discontinuations throughout this Cohort. 
8.0 PK Summary (insert tables, appendices as allowed by sponsor, if available): 
Subjects in the table below have been anonymized with an alphabet code. Given the way the cohort dosing was 
staggered and that samples through only 24 hours post dosing were available for one subject in the cohort, only 
geometric mean data is presented in order to maintain the blind. If the subject received active, their half-life and 
clearance parameters are not included in the mean. 
Additionally, the Cmax for 3 subjects was greater than 10000 ng/ml (the upper limit of quantitation in the assay) and 
there was not time to re-assay prior to the dose escalation meeting. Therefore, it is possible that the AUG and Cmax 
parameters are slightly underestimated. The anticipated geometric mean Cmax for this cohort was approximately 
10000-11000 ng/ml, so it is not anticipated that the Cmax concentrations are much greater than 10000 ng/ml, or 
that the AUG parameters are significantly higher than calculated below. 
No PK parameters met halting rules, and overall, the PK following a 10 mg/kg single dose administered by IV 
infusion was in line with anticipated exposure based on modeling and simulation and the exposure in Cohort 1 (5 
mg/kg dose). Furthermore, the simulated exposure for the next two dose levels is not anticipated to exceed the PK 
stopping criteria in the protocol. 
Geomean 
89.1 
9240 -l 
20400 
%CV 
21.6 
10.6 
12.8 
* 3 subjects had a Cmax > 10000 ng/ml 
EDSEXE 013 T 01 C 
~1!160,Jast 
(ng.H1m-Ll) 
30200 
14.1 
32400 
11.1 
20.9 
41.5 
285 
36600 
14.2 
35.4 
Page 4 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
The figure below shows the mean galidesivir concentration-time profiles for the first two cohorts of this study. 
100000 
...... 5 mg/kg 
-
..J 10000 
.... 10 mg/kg 
E -
O') 
C 
1000 
-... 
:~ 
100 
ti) 
CD 
"C 
«i 
10 
(!) 
1 
0 
50 
100 
time (h) 
9.0 Summary of Discussion at Dose Escalation Call: 
Based upon safety measures, tolerance, and pharmacokinetic results, the dose of 1 O mg/kg was well tolerated. 
The Safety Committee discussed data and agreed that data supports moving forward with dose escalation and with 
no change to the protocol. 
Current Dose Level: 10 mg/kg 
Next Dose Level: 
15 mg/kg 
Protocol changes required prior to next dose level administration (e.g. additional safety 
monitoring)? 
Yes 
D 
No 
~ 
EDSEXE 013 T 01 C 
Page 5 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIBNCES 
Daniel Dickerson, MD, PhD 
Principal Investigator 
PRA EDS-Lenexa 
~(.(uo__ w~YYWJ 
Diane Gesty-Palmer, MD, PhD 
Medical Monitor 
BioCryst Sr. Medical Director 
~~ 
}-A~ 
Amanda Mathis, PhD 
Director, Clinical Pharmacology 
BioCryst Pharmaceuticals 
EDSEXE 013 T 01 C 
Date 
Ol ~ 
Date 
01 f.-t-~ 
Date 
Wl9 
1/4\f) 
Dose Escalation Report 
BioCryst BCX4430-106 
01Feb2019 
Page 6 of 6 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
A PHASE 1 DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF GALIDESIVIR 
(BCX4430) ADMINISTERED AS SINGLE DOSES VIA INTRAVENOUS INFUSION IN 
HEALTHY SUBJECTS 
For BioCryst: 
DMID: 
For PRA: 
Protocol # : BCX4430-106 / DMID 18-0013 
PRA Study Code: 181 392 
Dose Escalation Report 
Single Ascending Dose 
Cohort 3: 15 mg/kg 
Report Date: 25Feb2019 
Diane Gesty-Palmer MD, PhD, Medical Monitor/Senior Medical Director 
Amanda Mathis, PhD, Clinical Pharmacologist 
Venus S. Shahamatdar, MD, Medical Monitor 
Kay M. Tomashek, MD, MPH, DTM, Medical Officer 
Carol Ostrye, RN, MPH, Clinical Project Manager 
DaDieJ Qickerson, MD, PhD, Principal lnyestigator 
Jamie Easum, APRN-BC, Co-Lead Sub-Investigator 
Lesa Davis, PA-C, Co-Lead Sub-Investigator 
Traci Goodwin, Clinical Study Manager 
Tim Theisen, Project Manager 
Safety Assessment Following Dose Administration of BCX4430 or Placebo to Healthy Volunteers 
EDSEXE 013 T 01 C 
Page 1 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


* 
PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
1.0 Subject Demographics, Dosing Date and Administration Times (All subjects dosed 
under fed conditions). 
 
13001 
13002 
01-071 
F 
13003 
01-078 
M 
13004 
M 
13005 
01-088 
M 
13006 
01-082 
F 
13007 
01-089 
F 
13008 
01-090 
F 
2.0 Adverse Events 
. -
05Feb2019 
28 
05Feb2019 
27 
07Feb2019 
54 
07Feb2019 
54 
07Feb2019 
34 
07Feb2019 
49 
07Feb2019 
37 
07Feb2019 
Dosing 
Time 
0930 
0935 
0930 
0935 
0940 
0945 
0950 
0955 
-
-
. . 
. 
. . . . . .  
. 
• 
• 
13001 
1 
Back Pain 
06Feb2019 1900 08Feb2019 
0730 
13002 
1 
Postnasal 
05Feb2019 1530 11Feb2019 
0800 
Drip 
13003 
1 
Headache 
07Feb2019 1700 08Feb2019 
0130 
13005 
1 
Abdominal 
10Feb2019 0700 
Bloating 
13005 
0700 13Feb2019 
2000 
13005 
3 
Anorexia 
10Feb2019 0700 
13007 
1 
Headache 
07Feb2019 1355 10Feb2019 
0545 
13007 
2 
Vomiting 
08Feb2019 0851 
08Feb2019 
0852 
3007 
3 
Syncope 
13Feb2019 1330 13Feb2019 
1310 
13007 
4 
Right Wrist 
13Feb2019 , 1330 
Pain 
13008 
5 
Urticaria 
20Feb2019 1600 
13008 
1 
Headache 
07Feb2019 0900 10Feb2019 
1900 
EDSEXE 013 T 01 C 
Discharge from 
Clinical Site 
(Date) 
09Feb2019 
09Feb2019 
11Feb2019 
11Feb2019 
11Feb2019 
11Feb2019 
11Feb2019 
11Feb2019 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Mild 
Relationship to 
IP 
Not Related 
Not Related 
Possibly 
Not Related 
Not Related 
Not Related 
Possibly 
Not Related 
Not Related 
Not Related 
Not Related 
Not Related 
Page 2 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEA LT H S CIENC E S 
Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
2.1 Adverse Event Comments (summarize findings from above table): 
II 
Adverse Event 
Comments 
1 
Back Pain 
Subject complains of aching lumbar back pain secondary to laying in 
bed. Initially pain rated 6/10 and after adding pillows to lumbar area and 
heating pad, pain decreased to 3/10. No treatment required. 
13002 
Postnasal Drip 
Subject complains of scratchy/itchy/sore throat with accompanying dry 
cough. No other associated symptoms. Humidifier placed in room and 
advised increased PO fluids. No treatment required. 
13003 
1 
Headache 
Subject complains of aching frontal headache rated 5/10 with no 
associated symptoms. No medications were required. 
13005 
1 
Abdominal Bloating 
Subject complains of abdominal bloating causing pain and discomfort 
rated 5-7/10. States nonnal bowel movements but unable to pass gas. 
Subject states diet here is very different than his usual diet at home 
where he predominantly eats a low fat diet. Abdominal exam showed 
positive bowel sounds, tenderness on palpation and tympanic 
percussion sounds noted in all quadrants. Advised increased 
ambulation. Continuing to improve as of 20Feb2019. 
13005 
2 
Nausea 
Subject states continuous nausea. Smell of food intensifies feelings of 
nausea. Subject did not consume any food on 10Feb2019 or 
11 Feb2019. Nausea resolved 13Feb2019. 
13005 
3 
Anorexia 
Subject states complete lack of appetite. Subject did not consume any 
food on 10Feb2019 or 11Feb2019. Appetite improvJng as of20Feb2019. 
13007 
Headache 
Subject complains of mild, dull, aching frontal headache rated 1/10 on 
pain scale. Advised ice pack and increased hydration. No medications 
were required. 
13007 
2 
Vomiting 
Subject vomited approximately 30cc of clear liquid. Subject states that 
she had just finished drinking 48 ounces of water and "it just came back 
up". No nausea or abdominal pain preceded the vomiting and subject 
proceeded to eat breakfast immediately after episode. 
13007 
3 
Syncope 
Subject states white taking a shower at home she briefly felt lightheaded 
and then "woke up on the floor". She states she "was only out for a 
minute". She denies preceding nausea, headache, visual changes or 
other associated symptoms. She states she felt fine after "waking up". 
Neuro exam normal at follow up. 
13007 
4 
Right Wrist Pain 
Subject fell on right wrist due to syncopal episode in shower. States 
pain at rest 1/10 and pain with movement 5-6/10. Physical exam 
showed pain on palpation predominately on dorsal surface, pain on 
flexion, extension and lateral movement of wrist. Swelling and 
ecchymosis noted on exam. Subject sent for xrays of wrist. Subject did 
not complete x-rays due to her personal choice. She reported 
improvement in swelling and pain with ability to use fully on 20Feb2019. 
Will monitor. 
13007 
5 
Urticaria 
Subject noticed itching around left axilla and shoulder blade region 
initially, then later noticed "rash" while looking in the mirror. On exam, 7 
lesions with wheal/flare response noted (right 4th proximal phalynx, left 
axilla, 4 X infrascapular region and 1 X inframedial scapula). Lesions 
are approximately 15-25mm with increase flare to 40mm and wheals 
approximately 15-20mm after scratching. Subject states ate shrimp for 
lunch approximately 2.5-3 hours prior to noticing lesions. No oral or 
respiratory symptoms. Photos taken. 
EDSEXE 013 T 01 C 
Page 3 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


"JI~ 
P RAHEALTHSCIENCES 
Dose Esca
lat
ion Report 
B
ioCryst BCX4430-106 
25Feb2019 
13008 
Headache 
Subject complained of bitemporal headache rated 5/10, at onset, which 
decreased to 1-2/10 shortly after that. No associated symptoms and no 
medications were required for treatment. 
3.0 Safety Lab Data: (Summary of significant or notable lab results 
) 
 
 
.I.. • 
4 
• 
. 
. 
. 
. 
. . 
Lab Test 
Result 
Range 
 
13001 
01-064 
M 
13001 
01-064 
M 
13002 
01-071 
F 
13002 
01-071 
F 
13003 
01-078 
M 
13003 
01-078 
M 
13004 
13004 
13004 
13004 
01-080 
M 
13004 
01-080 
M 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
13005 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
01-088 
M 
13005 
01-088 
M 
01-088 
M 
EDSEXE 013 T01 C 
32 
32 
28 
28 
27 
27 
54 
54 
54 
54 
54 
54 
54 
54 
54 
54 
54 
54 
07Feb2019 
08Feb2019 
05Feb2019 
07Feb2019 
07Feb2019 
10Feb2019 
10Feb2019 
11Feb2019 
07Feb2019 
08Feb2019 
08Feb2019 
09Feb2019 
09Feb2019 
09Feb2019 
10Feb2019 
10Feb2019 
10Feb2019 
10Feb2019 
11Feb2019 
11Feb2019 
3 
4 
3 
4 
1 
2 
2 
3 
3 
3 
4 
4 
Glucose 
148 mg/dl 
(random) 
Glucose 
142 mg/dl 
(random) 
Glucose 
100 mg/dl 
Glucose 
144 mg/dl 
(random) 
Total Protein 
6.0 g/dl 
Glucose 
171 mg/dl 
(random) 
Albumin 
3.5 g/dl 
Glucose 
155 mg/dl 
(random) 
Glucose 
(random) 
144 mg/d 
47 U/L 
Total Protein 
6.0g/dl 
Total Protein 
5.8 g/dl 
Hemoglobin 
12.3 g/dl 
Glucose 
160mg/dl 
(random) 
Total Protein 
Hemoglobin 
12.5 g/dl 
Glucose 
147 mg/dl 
(random) 
Sodium 
134 mmol/L 
Total Protein 
5.5g/d
l 
Hemoglobin 
12.3 g/dl 
Glucose 
108 mg/dl 
Total Protein 
5.8g/d
l 
65-139 mg/dl 
65-139 mg/dl 
65-99 mg/dl 
65-139 mg/dl 
6.1-8.1 g/dl 
65-139 g/dl 
3.6-5.1 g/dl 
65-139 mg/dl 
13.2-17.1 g/dl 
6J-8.1 g/dl 
13.2-17.1 g/dl 
65-139 mg/dl 
134-146 
mmol/L 
6.1-8.1 g/dl 
13.2-17.1 g/dl 
65-99 mg/dl 
6. 1-8.1 g/dl 
Page 4 of 8 
1 
2 
1 
1 
2 
1 
1 
1 
2 
2 
2 
2 
Note: The above informat
ion serves to document the rev
iew of safety informat
ion for the referenced study. The informat
ion conta
ined in or 
appended to this report is not cons
idered a source document and has not been sub
jected to def
in
it
ive mon
itor
ing 
Str
ict
ly Conf
ident
ia
l. © 2004-2014, PRA Hea
lth Sc
iences. All r
ights reserved. 


~ 
PRAHE A LT H SCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
13005 
01-088 
M 
54 
11Feb2019 
5 
Hemoglobin 
12.6 g/dL 
13.2-17.1 g/dL 
13005 
01-088 
M 
54 
11Feb2019 
5 
WBC 
10.9 
3.8-10.8 
thousand/uL 
thousand/uL 
13005 
01-088 
M 
54 
13Feb2019 
Unsch 
Hemoglobin 
12.4 g/dL 
13.2-17.1 g/dL 
13005 
01-088 
M 
54 
21Feb2019 
Unsch 
Hemoglobin 
11.6 g/dL 
13.2-17.1 g/dL 
13005 
01-088 
M 
54 
21Feb2019 
Unsch 
ALT 
72 U/L 
9-46 U/L 
13006 
01-082 
F 
34 
07Feb2019 
Glucose 
114 mg/dL 
65-99 mg/dL 
13006 
01-082 
F 
34 
08Feb2019 
2 
Glucose 
155 mg/dL 
65-139 mg/dL 
(random) 
13006 
01-082 
F 
34 
10Feb2019 
4 
Glucose 
141 mg/dL 
65-139 mg/dL 
(random) 
13007 
01 -089 
F 
49 
07Feb2019 
Calcium 
8.5 mg/dL 
8.6-10.2 mg/dL 
13007 
01-089 
F 
49 
07Feb2019 
1 
Total Protein 
5.9 g/dL 
6.1-8.1 g/dL 
13007 
01-089 
F 
49 
07Feb2019 
1 
Albumin 
3.5 g/dL 
3.6-5.1 g/dL 
13007 
01-089 
F 
49 
07Feb2019 
Hemoglobin 
11.2 g/dL 
11 .7-15.5 g/dL 
13007 
01-089 
F 
49 
08Feb2019 
2 
Total Protein 
5.8 g/dL 
6.1-8.1 g/dL 
13007 
01-089 
F 
49 
08Feb2019 
2 
Hemoglobin 
11 .2 g/dL 
11 .7-15.5 g/dL 
13007 
01-089 
F 
49 
09Feb2019 
3 
Hemoglobin 
11.5 g/dL 
11.7-15.5 g/dL 
13007 
01-089 
F 
49 
10Feb2019 
4 
Hemoglobin 
11 .3g/dL 
11 .7-15.5 g/dL 
13008 
01-090 
F 
37 
07Feb2019 
1 
Calcium 
8.5 mg/dL 
8.6-10.2 mg/dL 
13008 
01-090 
F 
37 
07Feb2019 
1 
Total Protein 
6.0 g/dL 
6.1-8.1 g/dL 
13008 
01-090 
F 
37 
08Feb2019 
2 
RBC (UA) 
10-20 I HPF 
</= 2 /HPF 
(on menses) 
3.1 Actions Taken/Con Meds Administered Related to Adverse Events: 
. . 
Dose/Unit 
*There were no actions /con meds administered related to adverse events. 
Prescribed 
for: 
25Feb2019 
2 
1 
2 
3 
1 
3 
1 
1 
1 
2 
1 
1 
2 
4.0 Vital Signs Data (summary of clinically significant abnormal vital signs by subject# 
ana-time- point taken): 
-
-
-- ------
1 
*There were no vital signs which met the criteria for halting dosing in Section 11 .5.2 of the protocol. 
EDSEXE 013 T 01 C 
Page 5 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEA LT HSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
5.0 12-Lead ECG Data (summarize clinically significant abnormal changes by subject# 
and time point taken): There were no clinically significant ECG findings, and no ECG parameters met the 
criteria for halting the infusion stated in Section 7.6.3.2 of the protocol. 
6.0 Physical Examination Data (summarize clinically significant abnormal changes by 
subject# and time point performed): There were no clinically significant physical exam findings noted. 
7.0 Subject Discontinuations: There were no subject discontinuations throughout this Cohort. 
8.0 PK Summary (insert tables, appendices as allowed by sponsor, if available): 
Subjects in the table below have been anonymized with an alphabet code. Samples were quantifiable through 96 
hours in a
l
l subjects. The geometric mean (%CV) Cmax
, AUCo-24, and AUC0.
1ast were 17700 (16%) ng/ml, 33900 
(17%) ng.h/ml, and 44300 (19%) ng.h/ml. No PK parameters met halting rules outlined in the protocol. 
T ½ (h) 
Cmax (ng/ml) 
AUC0.
24h 
Cl (mL/h/kg) 
Vz (ml/kg) 
(ng.h/ml) 
126 
16500 
37700 
220 
39900 
-
-
-
-
-
-
-
------
N 
81.2 
17400 
32900 
283 
33100 
i--
-
--
-
-
-
-
-
-
-
-
I 
---
~ ------
78 
21200 
39600 
215 
24200 
l 
l 
76.9 
18800 
29900 
298 
33000 
Q 
74 
13200 
25700 
358 
38200 
-
-
-
-
-
-
--
-
R 
64.1 
20600 
40200 
237 
21900 
-
-
-
Geomean 
81.4 
17700 
33900 
264 
31000 
%CV 
26 
16 
17 
21 
23 
Geometric mean summary data from a
l
l three cohorts are summarized below. Data from Cohort 1 and 2 have been 
updated to include a
l
l quantifiable PK samples, through the follow up period. Exposure has increased roughly 
proportional to the increase in dose. Therefore, it can be anticipated that for cohort 4, a 20 mg/kg dose of 
galidesivir administered by IV infusion would result in a Cmax of approximately 24000 ng/ml and an AUC0-24 of 
approximately 45000 ng.h/ml, below the stopping criteria (median Al:JCo-24 of 52500 ng.h/ml) . 
• 
I  • 
-;;:;~ AUCo~i~rt~:,:_ 
•:1-(iig.'f,iin(>, 
~ 
t~;f~t~~~~~.': · 
~. 2~ 
:Cl·· 
(ml/h/kg) 
5 j 
110 (40) I 
5540 ~~  
10!00 (11) 
17100_ 
(24) 1 
237 (20) 
1 3noo (13) 
-
: 
: 
.. ~~  ::~d 
: 
~;:~:~: I-:::::~:*-::~:~:: +-::: :: :> 
t:!:: :::: 
*Note for cohort 1 and 2, PK has been quantitated through 21 days of sampling. AUC0.
1ast represents a longer 
per
iod than Cohort 
3. 
EDSEXE 013 T 01 C 
Page 6 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


* 
PRAHEA LT H SCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
The figure below shows the mean galidesivir concentration-time profiles for the first two cohorts of this study. 
100000 
..,._ 
i-> rnn/ku 
::J' 
E 10000 
0) 
C 
---
10 mg/kg 
-+-
15 mg/kg 
-... 
1000 
> 
V, 
Cl) 
"O 
c6 
100 
(!) 
10 
0 
50 
100 
time (h) 
9.0 Summary of Discussion at Dose Escalation Call: 
Adverse events for subjects 13005 and 13007 were extensively reviewed. Based upon safety measures, tolerance, 
and pharmacokinetic results, the dose of 15 mg/kg was well tolerated. The Safety Committee discussed data and 
agreed that data supports moving forward with dose escalation and with no change to the protocol. 
Current Dose Level: 15 mg/kg 
Next Dose Level: 20 mg/kg 
Protocol changes required prior to next dose level administration (e.g. additional safety 
monitoring)? 
Yes 
D 
No 
l'8:] 
EDSEXE 013 T 01 C 
Page 7 of 8 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Daniel Dickerson, MD, PhD 
Principal Investigator 
PRA EDS-Lenexa 
Diane Gesty-Palmer, MD, PhD 
Medical Monitor 
BioCryst Sr. Medical Director 
Amanda Mathis, PhD 
Director, Clinical Pharmacology 
BioCryst Pharmaceuticals 
EDSEXE 013 T 01 C 
Date 
Date 
Dose Escalation Report 
BioCryst BCX4430-106 
25Feb2019 
i/iu /VJ l4 
Oat~ 
J 
Page 8 of 8 
Note: The above information serves to aocument the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
A PHASE 1 DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF GALIDESIVIR 
(BCX4430) ADMINISTERED AS SINGLE DOSES VIA INTRAVENOUS INFUSION IN 
HEAL THY SUBJECTS 
For BioCryst: 
DMID: 
For PRA: 
Protocol #: BCX4430-106 / DMID 18-0013 
PRA Study Code: 181392 
Dose Escalation Report 
Single Ascending Dose 
Cohort 4: 20 mg/kg 
Report Date: 26Mar2019 
Diane Gesty-Palmer MD, PhD, Medical Monitor/Senior Medical Director 
Amanda Mathis, PhD, Clinical Pharmacologist 
Venus S. Shahamatdar, MD, Medical Monitor 
Kay M. Tomashek, MD, MPH, DTM, Medical Officer 
Carol Ostrye, RN, MPH, Clinical Project Manager 
Daniel Dickerson, MD, PhD, Principal Investigator 
Jamie Easum, APRN-BC, Co-Lead Sub-Investigator 
Lesa Davis, PA-C, Co-Lead Sub-Investigator 
Traci Goodwin, Clinical Study Manager 
Tim Theisen, Project Manager 
Safety Assessment Following Dose Administration of BCX4430 or Placebo to Healthy Volunteers 
EDSEXE 013 T 01 C 
Page 1 of 7 
Note: The above information seNes to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reseNed. 


* 
PRAHEALTHSC IENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
1.0 Subject Demographics, Dosing Date and Administration Times (All subjects dosed 
under fed conditions). 
. 
. 
... 
• 
14001 
01-126 
M 
39 
06Mar2019 
0900 
14002 
01-124 
M 
45 
06Mar2019 
0905 
14003 
01-151 
F 
25 
08Mar2019 
0900 
. F 
28 
08Mar2019 
0905 
14005 
01-161 
F 
23 
08Mar2019 
0910 
14004 
01-130 
M 
42 
08Mar2019 
0915 
14007 
01-138 
M 
21 
08Mar2019 
0920 
14008 
01-157 
M 
38 
08Mar2019  
0925 
2.0 Adverse Events 
.
.
 
_
_
 
~ 
1 
Headache 
06Mar2019 
~20~ 
07Mar2019 
1500 
Mild 
2.1 Adverse Event Comments (summarize findings from above table): 
 
Adverse Event 
·  
-
Comments 
. . 
. • 
. • 
• 
10Mar2019 
10Mar2019 
12Mar2019 
12Mar2019 
12Mar2019 
12Mar2019 
12Mar2019 
12Mar2019 
Relationship to 
IP 
Possibly 
14001 
Headache 
Subject states intermittent sharp and throbbing pain in frontal and 
temporal regions. Rates pain 8/1 0 at its worst. Subject believes it is due 
to caffeine withdrawal. Advised increased hydrati
on and rest. Pain 
resolved without medication. 
3.0 Safety Lab Data: (Summary of significant or notable lab results) 
 
14001 
01-126 
M 
39 
14001 
01-126 
M 
39 
14001 
01-126 
M 
39 
14001 
01-126 
M 
39 
14001 
01-126 
M 
39 
EDSEXE 013 T 01 C 
Labora_
tory 
Collection 
Date 
06Mar2019 
06Mar2019 
06Mar2019 
07Mar2019 
07Mar2019 
 
Lab Test 
Result 
1 
Total Protein 
5.4 g/dl 
1 
Albumin 
3.4 g/dl 
1 
Hemoglobin 
12.6 g/dl 
2 
Total Protein 
6.0 g/dl 
2 
Hemoglobin 
13.1 g/dl 
Range 
6.1-8.1 g/dl 
3.6-5.1 g/dl 
13.2-17.1 g/dl 
6.1-8.1 g/dl 
13.2-17.1 g/dl 
Page 2 of 7 
3 
1 
2 
1 
1 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
14001 
01-126 
M 
39 
08Mar2019 
3 
Total Protein 
5.9 g/dL 
6.1-8.1 g/dL 
1 
14001 
01-126 
M 
39 
08Mar2019 
3 
Hemoglobin 
12.9 g/dL 
13.2-17.1 g/dL 
1 
14001 
01-126 
M 
39 
09Mar2019 
4 
Total Protein 
5.9 g/dL 
6.1 -8.1 g/dL 
1 
14001 
01 -126 
M 
39 
09Mar2019 
4 
Hemoglobin 
12.9 g/dL 
13.2-17.1 g/dL 
1 
14001 
01-126 
M 
39 
10Mar2019 
5 
PT 
11.6 sec 
9.0-11 .5sec 
1 
14001 
01 -126 
M 
39 
10Mar2019 
5 
Total Protein 
5.9 g/dL 
6.1-8.1 g/dL 
1 
14002 
01-124 
M 
45 
06Mar2019 
1 
Total Protein 
5.9 g/dL 
6.1-8.1 g/dL 
1 
14002 
01-124 
M 
45 
07Mar2019 
2 
Total Protein 
6.0 g/dL 
6.1-8.1 g/dL 
1 
14002 
01-124 
M 
45 
10Mar2019 
5 
PT 
11 .8 sec 
9.0-11.5 sec 
1 
14003 
01 -151 
F 
25 
08Mar2019 
1 
Calcium 
8.2 mg/dL 
8.6-10.2 mg/dL 
2 
14003 
01-151 
F 
25 
09Mar2019 
2 
Calcium 
8.5 mg/dL 
8.6-10.2 mg/dL 
1 
14003 
01-151 
F 
25 
12Mar2019 
5 
PT 
11 .6 sec 
9.0-11.5sec 
1 
14006 
F 
28 
08Mar2019 
1 
Calcium 
8.5 mg/dL 
8.6-10.2 mg/dL 
1 
14005 
01-161 
F 
23 
09Mar2019 
2 
WBC 
3.1 
3.8-10.8 
1 
Thousand/uL 
thousand/uL 
14005 
01-161 
F 
23 
10Mar2019 
WBC 
3.8-10.8 
1 
thousand/uL 
14005 
01-161 
F 
23 
10Mar2019 
ANG 
1500-7800 
1 
cells/uL 
14005 
01-161 
F 
23 
11Mar2019 
WBC 
3.0 
3.8-10.8 
1 
Thousand/uL 
thousand/uL 
14005 
01-161 
F 
23 
11Mar2019 
ANG 
1434 cells/uL 
1500-7800 
1 
cells/uL 
14005 
01-161 
F 
23 
12Mar2019 
PT 
9.0-11.5 sec 
1 
14004 
01-130 
M 
42 
08Mar2019 
1 
Absolute 
1163 cells/uL 
1500-7800 
1 
Neutrophils 
cells/uL 
14004 
01-130 
M 
42 
12Mar2019 
5 
PT 
12.0 sec 
9.0-11 .5 sec 
1 
14007 
01 -138 
M 
21 
10Mar2019 
3 
Glucose 
141 mg/dL 
65-139 mg/dL 
1 
(random) 
14007 
01-138 
M 
21 
11Mar2019 
4 
Glucose 
166 mg/dL 
65-139 mg/dL 
2 
(random) 
14007 
01-138 
M 
5 
PT 
12.4 sec 
1 
14008 
01-157 
M 
39 
09Mar2019 
2 
Glucose 
175 mg/dL 
65-139 mg/dL 
2 
(random) 
14008 
01-157 
M 
39 
10Mar2019 
3 
Glucose 
170 mg/dL 
65-139 mg/dL 
2 
(random) 
14008 
01-157 
M 
39 
11Mar2019 
4 
Glucose 
149 mg/dL 
65-139 mg/dL 
1 
(random) 
EDSEXE 013 T 01 C 
Page 3 of 7 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


I 
I 
PRA H EALT H SCIENCES 
3.1 Actions Taken/Con Meds Administered Related to Adverse Events: 
I 
• 
I• . 
• I 
I . • 
I .. 
*There were no actions /con meds administered related to adverse events. 
. . 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
I • I 
4.0 Vital Signs Data (summary of clinically significant abnormal vital signs by subject# 
and time point taken): 
Screening# ''=M/F 
•..- --
. 
--
. 
' 
~' 
~ . . - - -
:_. 
- . 
Date -
Values 
*There were no vital signs which met the criteria for halting dosing in Section 11 .5.2 of the protocol. 
5.0 12-Lead ECG Data (summarize clinically significant abnormal changes by subject# 
· 
p · 
a 
1 
: 
llere we e n clinically significant C 
findings, and no ECG parameters met the 
criteria for halting the infusion stated in Section 7.6.3.2 of the protocol. 
6.0 Physical Examination Data (summarize clinically significant abnormal changes by 
subject# and time point performed): There were no clinically significant physical exam findings noted. 
7.0 Subject Discontinuations: There were no subject discontinuations throughout this Cohort. 
8.0 PK Summary (insert tables, appendices as allowed by sponsor, if available): 
Subjects in the table below have been anonymized with an alphabet code. PK presented in this report is based on 
nominal sampling times. Samples were available through 24 hours in all subjects and were quantifiable through 24 
hours. The geometric mean (%CV) Cmax and AUCo-24 were 20500 (16%) ng/ml and 44600(13%) ng.h/ml. No PK 
parameters met halting rules outlined in the protocol. 
T ½ (h) 
Cmax (ng/ml) 
s 
NR 
25500 
T 
NR 
19900 
u 
NR 
17000 
V 
NR 
19900 
w 
NR 
24100 
X 
NR 
17900 
Geomean 
NR 
20500 
%CV 
16.4 
EDSEXE 013 T 01 C 
AUCo.24 
(ng.h/ml) 
44200 
39800 
42800 
43900 
51200 
46500 
44600 
8.6 
Cl (ml/h/kg) 
382 
487 
449 
415 
357 
349 
404 
13.4 
Vz (ml/kg) 
12100 
2610 
2650 
8110 
8190 
13400 
6490 
58 
Page 4 of 7 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
Across cohorts, galidesivir exposure increased roughly proportional to the increase in dose, with a 3. 7-fold increase 
in geometric mean Cmax and a 4.1-fold increase in AUCo-24 with a 4-fold increase in dose. 
l oose 
5 
10 
15 
110 (40) 
102 (20) 
81.4 (26) - · 
I 
I 
5540 (8) 
10300 (21) 
17700(16) 
I 
• 
10800(11) 
20800 (14) 
33900 (17) 
~~ AUCo-ia~t '."iT, .. 
\':J(ng.h/ml.:'.f :· 
~ ·/itJ1t:: ~). ·, :,~~~: 
17100 (24) 
32300 (16) 
59600 (21) 
237 (20) 
270 (16) 
228 (22) 
· Vz (ml/kg) 
37700 (13) 
39800 (29) 
56400 (12) 
20 
I 
NR 
I 20500 (16) 
44600 (9) 
44600 (9) 
404 (13) 
1 
NR 
1 
*Note for cohort 1,2 and 3, PK has been quantitated through 21 days of sampling. AUC0-1ast represents a longer period than 
Cohort 3. 
The figures below shows the mean galidesivir concentration-time profiles for all cohorts of this study. As Cohort 4 
only has PK available through 24 hours, the figure on the right shows concentration-time profiles for all cohorts 
through 24 hours. 
::r 
E 
c, 
.s 
~ 
·;; 
"iii 
QJ 
~ 
iii 
(!) 
100000 
10000 
1000 
100 
10 
0 
50 
time (h) 
100 
..... 5 mg/kg 
...... 10 mg/kg 
..... 15 mg/kg 
-+ 20 mg/kg 
::r 
E 
c, 
.s 
~ 
·;; 
"iii 
QJ 
~ 
iii 
(!) 
100000 
10000 
1000 
100 
10 
9.0 Summary of Discussion at Dose Escalation Call: 
0 
4 
8 
12 
16 
20 
24 
time (h) 
..... 5 mg/kg 
...... 10 mg/kg 
..... 15mg/kg 
-+ 20 mg/kg 
Based upon safety measures, tolerance, and pharmacokinetic results, the dose of 20 mg/kg was well tolerated. 
The Safety Committee discussed data and agreed that data supports safety of 20 mg/kg dose. 
The safety committee reviewed previous SAEs and outstanding AEs: 
Subject 12007, in Cohort 2, had a pregnancy that resulted in a spontaneous abortion. Hospital records have been 
obtained but follow-up gynecologic records were never received. The information was reviewed with the safety 
committee and the final SAE report will be submitted on 27-Mar-2019. The Pl deemed that the SAE was unlikely 
related to study drug due to subject's age and prior history of spontaneous abortion. The Sponsor concurred that 
the spontaneous abortion was unlikely related to study drug. In addition, this assessment is consistent with the 
reported preclinical toxicology. 
EDSEXE 013 T 01 C 
Page 5 of 7 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
Subject 13005, in Cohort 3, reported to the Pl on 26-Mar-2019 that he was in the hospital and had a "mass on his 
stomach". Hospital records are not yet available. The subject had four adverse events on study that are potentially 
related to his stomach mass. On day 1 of the study (08-Feb-2019) the subject developed anemia which was 
worked up and found to be an iron deficiency anemia with a negative stool hemoccult, normal reticulocyte count, 
and low serum iron. On day 3 of the study (10-Feb-2019) he reported abdominal bloating, nausea, and anorexia. 
The stomach mass was reported as an SAE on 26-Mar-2019 and the Pl deemed it to be unrelated to study drug 
because potential mass related adverse events began within days after dosing. All members of the safety 
committee, including the medical monitor, concur with this assessment. 
Subject 13007, in Cohort 3, developed urticaria which was evaluated by a dermatologist and found to be vascular 
urticaria on biopsy. Following dermatology workup, the subject noted working and sleeping at a facility that was 
found to have bedbugs. The follow-up dermatology report lists bedbugs as consistent with the subject's vascular 
urticaria. This adverse event was deemed by Pl to not be related to study drug based on subject history and 
dermatology report. 
Current Dose Level: 20 mg/kg 
Next Dose Level: 
NA 
Protocol changes required prior to next dose level administration (e.g. additional safety 
monitoring)? 
Yes 
D 
No 
~ 
The protocol has completed enrollment of all cohorts and therefore there will be no further doses administered. 
This report is intended to summarize the exposure of BCX4430 observed in cohort 4. 
There were no stopping criteria met in any cohort of the study 
There were no trends or dose relatedness to any laboratory abnormalities. 
Overall, galidesivir was well tolerated and has an acceptable safety profile, supporting further clinical development. 
EDSEXE 013 T 01 C 
Page 6 of 7 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved. 


PRAHEALTHSCIENCES 
Daniel Dickerson, MD, PhD 
Principal Investigator 
PRA EDS-Lenexa 
Diane Gesty-Palmer, MD, PhD 
Medical Monitor 
BioCryst Sr. Medical Director 
Amanda Mathis, PhD 
Director, Clinical Pharmacology 
BioCryst Pharmaceuticals 
EDSEXE 013 T 01 C 
Date 
Dose Escalation Report 
BioCryst BCX4430-106 
26Mar2019 
·2e lfv\oru\.t1 1A)te,, 
Date 
Page 7 of 7 
Note: The above information serves to document the review of safety information for the referenced study. The information contained in or 
appended to this report is not considered a source document and has not been subjected to definitive monitoring 
Strictly Confidential. © 2004-2014, PRA Health Sciences. All rights reserved.