(W0930-02-11) VLX-1005 Multiple Ascending Dose Pharmacokinetics

Purpose: To evaluate the pharmacokinetics (PK) of VLX-1005, a novel inhibitor of 12-lipoxygenase for the treatment of heparin induced thrombocytopenia, following IV administration to healthy volunteers in a multiple ascending dose study (clinical study protocol VLX-1005-001).

Methods: Four cohorts of healthy volunteers (8 active / 2 placebo) were randomized to receive multiple doses of 100 mg, 200 mg, and 400 mg after a one-hour or 400 mg after a four-hour infusion once daily for 5 days. Plasma and urine samples were collected after dosing on day 1 and day 5. Bioanalysis: Plasma and urine samples were analyzed for VLX-1005 with LC/MS/MS methods with lower limits of quantitation of 1 ng/mL. Pharmacokinetic Analysis: PK parameters for VLX-1005 were calculated by non-compartmental analysis.

Results: After IV administration of VLX-1005 once-daily for five days, there were dose-related increases in the geometric mean plasma concentrations, Cmax and AUC(0-24) on days 1 and 5. Power model exponents for Cmax and AUC (estimate ± asymptotic standard error) did not include 1.0, demonstrating slightly less than dose-proportional increase over the 4-fold dose range. There was negligible excretion of unchanged VLX-1005 in urine.

Conclusion: Pharmacokinetics of VLX-1005 in healthy volunteers was characterized after once-daily IV administration for 5 days. The PK profile exhibits nearly dose proportional increases in exposure metrics after multiple doses. The PK information has been utilized to project doses for a drug-drug interaction study, VLX-1005-002, and the ongoing Phase 2 clinical trial, VLX-1005-003 (ALATHEA).

Acknowledgements: BioAgilytix conducted plasma and urine bioanalysis. William Kramer is a paid consultant to Veralox Therapeutics.


Figure 1. Geometric mean plasma concentrations of VLX-1005 after IV administration of 100 mg to 400 mg once-daily for 5 days to healthy subjects — linear (left panel) and semi logarithmic (right panel) axes.