A Study to Evaluate the Single Dose Safety, Tolerability and Pharmacokinetics of IV BCX4430

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Marburg Virus Disease

Intervention / Treatment
-----------------
* Drug: galidesivir
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: written informed consent males and non-pregnant, non-lactating females BMI 19.0-32.0 willing to abide by contraceptive requirements normal vitals willing to abide by study procedures and restrictions Exclusion Criteria: clinically significant medical condition or medical history or psychiatric condition or history of psychiatric condition abnormal cardiac finding, or laboratory/urinalysis abnormality at screening known family history of sudden death or long QT syndrome, family or personal history of QT prolongation, or arrhythmia that required medical intervention current participation in any other investigational drug study or participation in an investigational drug study within 3 months of screening visit use of prescription, OTC, or herbal medications during study or use of any specified medications within 30 days prior to study Recent or current history of alcohol or drug abuse Regular use of tobacco or nicotine products Positive serology for HBV, HCV, or HIV history of severe adverse reaction to or known sensitivity to any drug pregnant, lactating, or planning to become pregnant within 30 days of the study. Male subjects with pregnant female partners are excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galidesivir<br>Galidesivir IV infusion | Drug: galidesivir<br>* galidesivir IV infusion<br>|
| Placebo Comparator: placebo<br>Placebo IV infusion | Drug: placebo<br>* placebo IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Galidesivir Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events. | Any event reported on the subject's study record that occurred on or after the initiation of study drug was defined as treatment emergent (TEAE). | AEs were assessed and recorded from the time of signing the ICF through to the appropriate follow-up period, up to 23 days from IMP dosing on Day 1. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PK - Galidesivir Cmax (Maximum Observed Concentration of Drug) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points: Day 1 to Day 5: 0 hour (pre dose), halfway through the infusion (0.5 hour), 1 hour (end of the infusion), 1.25, 1.50, 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. Cmax for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). | Plasma PK parameters are based on sampling over a 21 day period | 
| Plasma PK - Galidesivir AUC (Area Under the Concentration vs. Time Curve) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points: Day 1 to Day 5: 0 hour (pre dose), halfway through the infusion (0.5 hour), 1 hour (end of the infusion), 1.25, 1.50, 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. AUC0-inf (AUC from time 0 extrapolated to infinite time) and AUC0-t (AUC from time 0 to time t, where t = the last quantifiable concentration) for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). | Plasma PK parameters are based on sampling over a 21 day period | 
| Galidesivir Renal Clearance | Urine was collected from subjects over a 96 hour period per protocol, analyzed for galidesivir concentrations. Urine PK parameters including CLR (renal clearance of unchanged drug cumulatively over all collection intervals or in a specific interval) were estimated in SAS for Windows v9.4 or higher (SAS Institute, Inc.) based on the recorded urine concentrations and volumes. | Urine PK parameters are based on sampling over a 96 hour period. |