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NCT03800173

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

Completed Phase 1 Results posted Last updated 23 July 2021
What this trial tests

Phase 1 trial testing galidesivir in Marburg Virus Disease in 32 participants. Completed in 30 April 2019.

Timeline
10 December 2018
Primary endpoint
30 April 2019
30 April 2019

Quick facts

Lead sponsorBioCryst Pharmaceuticals
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment32
Start date10 December 2018
Primary completion30 April 2019
Estimated completion30 April 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

BioCryst Pharmaceuticals — full company profile →

Who can join

Adults 18 to 55, any sex, with Marburg Virus Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Galidesivir Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events. Primary · 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).

Subjects with at least 1 TEAE
GroupValue95% CI
Placebo2
5 mg/kg Galidesivir0
10 mg/kg Galidesivir1
15 mg/kg Galidesivir4
20 mg/kg Galidesivir1
Not related TEAEs
GroupValue95% CI
Placebo2
5 mg/kg Galidesivir0
10 mg/kg Galidesivir1
15 mg/kg Galidesivir2
20 mg/kg Galidesivir0
Related TEAEs
GroupValue95% CI
Placebo0
5 mg/kg Galidesivir0
10 mg/kg Galidesivir0
15 mg/kg Galidesivir2
20 mg/kg Galidesivir1
Mild TEAE
GroupValue95% CI
Placebo2
5 mg/kg Galidesivir0
10 mg/kg Galidesivir1
15 mg/kg Galidesivir3
20 mg/kg Galidesivir1
Moderate TEAE
GroupValue95% CI
Placebo0
5 mg/kg Galidesivir0
10 mg/kg Galidesivir0
15 mg/kg Galidesivir0
20 mg/kg Galidesivir0
Severe TEAE
GroupValue95% CI
Placebo0
5 mg/kg Galidesivir0
10 mg/kg Galidesivir0
15 mg/kg Galidesivir1
20 mg/kg Galidesivir0
Subjects with at least 1 SAE
GroupValue95% CI
Placebo0
5 mg/kg Galidesivir0
10 mg/kg Galidesivir1
15 mg/kg Galidesivir1
20 mg/kg Galidesivir0
Subject Discontinuation due to AE
GroupValue95% CI
Placebo0
5 mg/kg Galidesivir0
10 mg/kg Galidesivir0
15 mg/kg Galidesivir0
20 mg/kg Galidesivir0
Plasma PK - Galidesivir Cmax (Maximum Observed Concentration of Drug) Secondary · 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.).

GroupValue95% CI
5 mg/kg Galidesivir5540± 7.8
10 mg/kg Galidesivir10300± 22.3
15 mg/kg Galidesivir17730± 17.5
20 mg/kg Galidesivir20490± 16.2
Plasma PK - Galidesivir AUC (Area Under the Concentration vs. Time Curve) Secondary · 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 wi

AUC0-inf
GroupValue95% CI
5 mg/kg Galidesivir21160± 23.0
10 mg/kg Galidesivir37080± 14.5
15 mg/kg Galidesivir65860± 21.9
20 mg/kg Galidesivir81230± 14.3
AUC0-t
GroupValue95% CI
5 mg/kg Galidesivir17150± 21.0
10 mg/kg Galidesivir32360± 17.4
15 mg/kg Galidesivir59590± 22.0
20 mg/kg Galidesivir73350± 14.1
Galidesivir Renal Clearance Secondary · 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.

GroupValue95% CI
5 mg/kg Galidesivir9.305± 16.7
10 mg/kg Galidesivir11.66± 17.8
15 mg/kg Galidesivir11.51± 14.5
20 mg/kg Galidesivir7.131± 90.4

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs were assessed and recorded from the time of signing the ICF through to the appropriate follow-up visit, up to 23 days from IMP dosing on Day 1. All AEs were graded for severity using the modified 2014 DMID Adult Toxicity Grading Scale. Any AEs not covered by the DMID criteria were assessed and classified into 1 of 3 clearly defined categories (mild, moderate, or severe).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/8 (0%)
Deaths: 0/8
5 mg/kg Galidesivir
Serious: 0/6 (0%)
Deaths: 0/6
10 mg/kg Galidesivir
Serious: 1/6 (17%)
Deaths: 0/6
15 mg/kg Galidesivir
Serious: 1/6 (17%)
Deaths: 0/6
20 mg/kg Galidesivir
Serious: 0/6 (0%)
Deaths: 0/6

Serious adverse events (2 terms)

ReactionSystemPlacebo5 mg/kg Galidesivir10 mg/kg Galidesivir15 mg/kg Galidesivir20 mg/kg Galidesivir
gastrooesophageal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)—————
Abortion spontaneousPregnancy, puerperium and perinatal conditions—————
Other adverse events (15 terms — click to expand)

ReactionSystemPlacebo5 mg/kg Galidesivir10 mg/kg Galidesivir15 mg/kg Galidesivir20 mg/kg Galidesivir
HeadacheNervous system disorders—————
SyncopeNervous system disorders—————
Abdominal DistensionGastrointestinal disorders—————
Abdominal painGastrointestinal disorders—————
NauseaGastrointestinal disorders—————
VomitingGastrointestinal disorders—————
ArthralgiaMusculoskeletal and connective tissue disorders—————
Back painMusculoskeletal and connective tissue disorders—————
GastroenteritisInfections and infestations—————
UrticariaSkin and subcutaneous tissue disorders—————
Hepatic lesionHepatobiliary disorders—————
Iron deficiency anaemiaBlood and lymphatic system disorders—————
LeukocytosisBlood and lymphatic system disorders—————
Decreased appetiteMetabolism and nutrition disorders—————
Upper airway cough syndromeRespiratory, thoracic and mediastinal disorders—————

Most-reported serious reactions: gastrooesophageal cancer, Abortion spontaneous.

Data from ClinicalTrials.gov NCT03800173 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics.
    Arshad U, Pertinez H, Box H, Tatham L, et al · · 2020 · cited 115× · PMID 32438446 · DOI 10.1002/cpt.1909
  2. SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19.
    Vicenti I, Zazzi M, Saladini F. · · 2021 · cited 77× · PMID 33475441 · DOI 10.1080/13543776.2021.1880568
  3. Pathogenicity and virulence of West Nile virus revisited eight decades after its first isolation.
    Saiz JC, Martín-Acebes MA, Blázquez AB, Escribano-Romero E, et al · · 2021 · cited 35× · PMID 33843445 · DOI 10.1080/21505594.2021.1908740
  4. Current status of small molecule drug development for Ebola virus and other filoviruses.
    Edwards MR, Basler CF. · · 2019 · cited 35× · PMID 31003196 · DOI 10.1016/j.coviro.2019.03.001
  5. Potential repurposed SARS-CoV-2 (COVID-19) infection drugs.
    Abuo-Rahma GEA, Mohamed MFA, Ibrahim TS, Shoman ME, et al · · 2020 · cited 25× · PMID 35515773 · DOI 10.1039/d0ra05821a
  6. Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.
    Li X, Peng T. · · 2021 · cited 25× · PMID 34017257 · DOI 10.3389/fphar.2021.660710
  7. Selected nucleos(t)ide-based prescribed drugs and their multi-target activity.
    Pastuch-Gawołek G, Gillner D, Król E, Walczak K, et al · · 2019 · cited 23× · PMID 31634460 · DOI 10.1016/j.ejphar.2019.172747
  8. Coronavirus in human diseases: Mechanisms and advances in clinical treatment.
    Lin P, Wang M, Wei Y, Kim T, et al · · 2020 · cited 21× · PMID 33173860 · DOI 10.1002/mco2.26

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