Abstract
Purpose
SY-004, a dual-acting full glucokinase activator, is under development to provide
a dose-dependent improvement of glucose control. This study aimed to assess the tolerability,
safety, and pharmacokinetic and pharmacodynamic properties of SY-004 in healthy Chinese
adults.
Methods
Two study participants were administered 2 mg of SY-004 in the 2-mg cohort, whereas
6 study participants were randomized with 4 study participants receiving SY-004 and
2 receiving placebo in the 20-mg cohort. In each of other 3 dose cohorts (40, 80,
and 120 mg), 12 participants were randomized in a 10:2 ratio to receive single oral
SY-004 capsules or placebos. Drug concentrations, glucose and insulin levels, and
safety data were assessed and analyzed. Noncompartmental analysis was used to determine
SY-004 pharmacokinetic parameters.
Findings
SY-004 was generally well tolerated. Nine of the 44 study participants reported 17
treatment-related adverse events, and most treatment-related adverse events were mild.
SY-004 had approximately dose-proportional increases in systemic exposure. The mean
t½ ranged from 37.6 to 49.9 hours, and CL/F values ranged from 67.1 to 110 L/h across
all doses. The cumulative amounts of the unchanged drug excreted in urine were very
low, accounting for no more than 1.53% of the given doses. No significant difference
in sex was observed in pharmacokinetic parameters. The pharmacodynamic response appeared
to slightly correlate with dose.
Implications
SY-004, a new potential glucokinase activator, had favorable safety profiles and good
PK characteristics. The glucose-lowering effects were slightly dose related. The SY-004
data in healthy Chinese adults supports further development. ClinicalTrials.gov identifier:
NCT03171623.
Key words
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Article info
Publication history
Published online: January 26, 2022
Accepted:
December 17,
2021
Identification
Copyright
© 2022 Elsevier Inc.
