Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Drug development, Treatment Considerations
Objectives: The objective of this study was to evaluate the safety, tolerability and pharmacokinetics (PK) of OKL-1111 after single intravenous dosing in normal healthy male subjects. In addition, the pharmacodynamic (PD) response of OKL-1111 in the absence or presence of dabigatran was assessed ex vivo.
Design: A single-center, randomized, placebo-controlled, double-blind, single-ascending dose, alternating-group, partial crossover trial in healthy adult men (n=24). Next to standard hematology and clinical chemistry assays, possible prothrombotic effects were measured by means of measuring d-dimer formation and thrombin-antithrombin (TAT) complexes. A potential PD response of OKL-1111 was measured ex vivo in thrombin generation analyses (TGA).
Results: OKL-1111 was well tolerated up to a single intravenous administration of 1000 mg. There was no discernible difference from placebo or presence of dose-relationship in the number or severity of reported adverse events. No Serious Adverse Events were reported, and there were no indications of thrombosis (d-dimer, TAT). In addition, there were no treatment related effects of clinical significance on any safety and tolerability assessments. PK showed clear dose proportionality as expected for a mainly renally cleared compound and was not affected when individuals received dabigatran. OKL-1111 at a single dose of 1000mg reduced the dabigatran-induced lagtime increase in TGA.
Discussion: OKL-1111, to our knowledge the first fully universal reversal agent and the only clopidogrel reversal agent, can be safely administered to volunteers up to 1000mg, without (serious) adverse events.
Disclosures: Spaans: Curare Consulting: Current equity holder in private company; Alveron Pharma: Consultancy. Wilkes: Hammersmith Medicine Research: Current Employment. Schreurs: Alveron Pharma: Current Employment, Current holder of stock options in a privately-held company. Zwiers: Alveron Pharma: Consultancy, Current equity holder in private company, Current holder of stock options in a privately-held company; Okklo Life Sciences: Current equity holder in private company; PLG: Current equity holder in private company; Formynox BV: Current equity holder in private company; Sanquin research: Research Funding; Zwiers Pharma: Current equity holder in private company. Beyrath: Curare Consulting: Consultancy, Current Employment; Alveron Pharma: Consultancy. Patel: Alveron Pharma: Current Employment, Current holder of stock options in a privately-held company. Bakhtiari: Sanquin Research: Current Employment. Meijers: ECAT: Speakers Bureau; Synapse Research Institute: Consultancy; Alveron Pharma: Consultancy. Peters: Formynox: Current equity holder in private company; BioPharma Matters: Current equity holder in private company; Alveron Pharma: Consultancy, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties; Sanquin Research: Research Funding; Okklo Life Sciences: Current equity holder in private company.
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