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

Phase 1

Completed

Conditions: Marburg Virus Disease

Interventions: Drug: placebo
Drug: galidesivir

Registration Number: NCT03800173

Lead Sponsor: BioCryst Pharmaceuticals

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	Placebo IV infusion
Galidesivir	galidesivir	Galidesivir IV infusion

Primary Outcome Measures

Name	Time	Method
Galidesivir Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events.	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.	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).

Secondary Outcome Measures

Name	Time	Method
Galidesivir Renal Clearance	Urine PK parameters are based on sampling over a 96 hour period.	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.
Plasma PK - Galidesivir Cmax (Maximum Observed Concentration of Drug)	Plasma PK parameters are based on sampling over a 21 day period	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 - Galidesivir AUC (Area Under the Concentration vs. Time Curve)	Plasma PK parameters are based on sampling over a 21 day period	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.).