Safety, tolerability and pharmacokinetic profile of recombinant human tissue kallikrein, DM199, after intravenous and subcutaneous administration in healthy volunteers
Background: DM199 is a recombinant form of human tissue kallikrein (KLK1) that is being developed for ischemia-related diseases such as acute ischemic stroke. KLK1 is an important serine protease that promotes vasodilation and microcirculation in multiple tissues. Preclinical stroke studies demonstrate that KLK1 treatment promotes vasodilation, angiogenesis, prevents inflammation, and cerebral cell death.
Methods: The safety and tolerability, as well as the pharmacokinetic profile of DM199 was investigated in a Phase 1B clinical trial following an intravenously (IV) or subcutaneous (SC) administration. Part A was a single ascending IV infusion of DM199 and Part B involved a single IV infusion and single SC dose in two different groups.
Results: For both routes of administration, DM199 was found to be safe and well tolerated at all doses given, albeit the PK profile differed between routes with respect to the time to maximum concentration and plasma half-life. Importantly, DM199 did not influence blood coagulation parameters, suggesting it could be safely used with other stroke treatments like tPA.
Conclusions: Together, these results support the design of future studies to test the efficacy of DM199 in ischemic related diseases including in acute ischemic stroke (AIS).
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