Background: This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.
Methods: This study comprised a randomized, double-blind, placebo-controlled, single-dose escalation phase and an open-label, multiple-dose escalation phase. 94 subjects received intramuscular injections of QHRD106/placebo only once and 30 subjects received QHRD106 four times. 6 subjects received 0.15 PNA units UKN intravenously for 7 d. PK and PD analysis were conducted by using a electrochemiluminescent assay and a liquid chromatography/mass spectrometry methodology respectively. Cerebral circulation was assessed by the magnetic resonance imaging system.
Results: QHRD106 exhibited a slow absorption profile in the human body. Compared to UKN, QHRD106 induced changes in bradykinin concentration later, but with a noticeably prolonged duration. Compared to baseline, cerebral blood flow exhibited a significant improvement on d 7 after a single dose of 18,900 IU and an improvement from d 2 to d 14 after multiple dose of 8400 IU of QHRD106. QHRD106 appeared generally good safety and no severe adverse events occurred in all the groups.
Conclusions: This study provided initial evidence of potential treatment for ischemic strokes that the QHRD106 injection functioned as a safe and effective long-acting kallikrein drug.
Registration: This study was registered on ClinicalTrials.gov with the identifier NCT06380699 and NCT06388772.
Keywords: Kallikreins; cerebrovascular circulation; clinical trial; ischemic stroke.