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

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

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

Study Overview

• Status: Completed
• Conditions: Marburg Virus Disease
• Intervention / Treatment: Drug: galidesivir; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Galidesivir; Galidesivir IV infusion	Drug: galidesivir; galidesivir IV infusion
Placebo Comparator: placebo; Placebo IV infusion	Drug: placebo; placebo IV infusion

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.

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Daniel Dickerson, MD, PhD, PRA Health Sciences

Publications and helpful links

General Publications

• Mathis A, Collins D, Dobo S, Walling DM, Sheridan WP, Taylor R. Pharmacokinetics and Safety of the Nucleoside Analog Antiviral Drug Galidesivir Administered to Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2022 Apr;11(4):467-474. doi: 10.1002/cpdd.1037. Epub 2022 Feb 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2018
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Virus Diseases; Marburg Virus Disease; Anti-Infective Agents; Antiviral Agents; Galidesivir
• Other Study ID Numbers: BCX4430-106; 272201300017C-18-0-1 (U.S. NIH Grant/Contract); DMID18-0013 (Other Identifier: NIAID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No