Visual Abstract
Background: PB201, a dual-acting glucokinase activator (GKA), increases glucose stimulated insulin secretion, promotes glycogen synthesis and reduces hepatic glucose output by targeting both pancreatic and hepatic glucokinase. As a partial GKA, PB201 maintains efficacy while mitigates risk of hypoglycemia.
Methods: Totally 16 patients with T2DM were randomized to this 4-period crossover study. In each period, 1 of the 3 dose levels of PB201 (50/50mg, 100/50mg or 100/100 mg) or placebo was administrated before breakfast and lunch for 7 days. A 7 to 14-day washout separated each period. The primary endpoints were safety and PK profiles of PB201. Continuous glucose monitoring (CGM) system was also utilized. ClinicalTrials.gov NCT03973515.
Results: PB201 demonstrated dose-proportional increases in AUClast and Cmax. Elimination half-life ranged from 8.01 to 9.55 hours across all doses. No sex effect was observed in PK parameters. PB201 also showed dose-related effect in PD responses and good glycemic control (Table 1). No hypoglycemia or other drug-related adverse events were reported.
Conclusion: PB201 showed linear PK properties and provided efficient glycemic control in a dose-dependent manner. Meanwhile, it was safe and well tolerated by the subjects.
M. Xu: None. Pegbio study group: n/a.
