The study is designed to characterize the safety and tolerability of VLX-1005 and argatroban administered intravenously, either alone or in combination; and the pharmacokinetics and pharmacodynamics and potential interaction of both agents in a population of healthy subjects.
VLX-1005 is being developed as a treatment for heparin induced thrombocytopenia (HIT), a rare but life threatening illness. Currently, the anticoagulant argatroban remains the standard of care for treating HIT. However, this treatment remains inadequate due to both thrombosis and major bleeding complications that each may exceed 30% of treated HIT patients. These findings are significant to the later stage clinical development of VLX-1005 as a trial of VLX-1005 on top of argatroban therapy would require an understanding of any potential drug-drug interactions- whether direct or via metabolism. Specifically, coadministration of VLX-1005 with argatroban mandates an analysis of the potential effects on PK, pharmacodynamics and bleeding. The current study is designed to address these important questions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Measurement and comparison of the effects and potential interactions between VLX-1005 and argatroban on safety, tolerability, PK and PD
Measurement and comparison of the effects and potential interactions between VLX-1005 and argatroban on safety, tolerability, PK and PD
Celerion, Inc.
Lincoln, Nebraska, United States
Effects of argatroban on Cmax of VLX-1005
Measure the effects of argatroban on the maximum plasma concentration (Cmax) of VLX-1005
Time frame: 0 - 51 hours
Effects of VLX-1005 on Cmax of argatroban
Measure the effects of VLX-1005 on the maximum plasma concentration (Cmax) of argatroban
Time frame: 0 - 51 hours
Effects of argatroban on Tmax of VLX-1005
Measure the effects of argatroban on the time to maximum plasma concentration (Tmax) of VLX-1005
Time frame: 0 - 51 hours
Effects of VLX-1005 on Tmax of argatroban
Measure the effects of VLX-1005 on the time to maximum plasma concentration (Tmax) of argatroban
Time frame: 0 - 51 hours
Effects of argatroban on AUC(inf) of VLX-1005
Measure the effects of argatroban on the Area Under the Curve \[AUC(inf)\] of VLX-1005
Time frame: 0 - 51 hours
Effects of VLX-1005 on AUC(inf) of argatroban
Measure the effects of VLX-1005 on the Area Under the Curve \[AUC(inf)\] of argatroban
Time frame: 0 - 51 hours
Effects of VLX-1005 on whole blood aggregometry
The change in impedance from baseline by whole blood aggregometry will be measured to assess the effects of VLX-1005 on platelet aggregation
Time frame: 0 - 9 hours
Effects of argatroban on whole blood aggregometry
The change in impedance from baseline by whole blood aggregometry will be measured to assess the effects of argatroban on platelet aggregation
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Time frame: 0 - 9 hours
Effects of VLX-1005 on PFA-100
Change in PFA-100 (a platelet pharmacodynamic measure) from baseline, to assess the effects of VLX-1005 on platelet aggregation
Time frame: 0 - 9 hours
Effects of argatroban on PFA-100
Change in PFA-100 (a platelet pharmacodynamic measure) from baseline, to assess the effects of argatroban on platelet aggregation
Time frame: 0 - 9 hours
Safety as measured by incidence of Treatment Emergent Adverse Events
To assess the effects on subject safety of VLX-1005 and argatroban alone and in combination as measured by incidence of Treatment Emergent Adverse Events as assessed by CTCAE, ver 5.0.
Time frame: 0 - 30 days
Effects of VLX-1005 on 12-HETE
12-hydroxyeicosatetraenoic acid (12-HETE), a platelet biomarker, will be measured to assess the effects of VLX-1005 on its production
Time frame: 0 - 12 hours
Effects of argatroban on 12-HETE
12-HETE, a platelet biomarker, will be measured to assess the effects of argatroban on its production
Time frame: 0 - 12 hours