Safety, tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-naïve Chinese patients with type 2 diabetes: a randomised controlled, crossover, single-centre phase 1 trial

A multicentre, randomized, double‐blind, parallel, active‐ and placebo‐controlled Phase 3 clinical study of the glucokinase activator PB‐201 in treatment‐naive patients with type 2 diabetes mellitus: A study protocol

“…The two Phase 2 studies in which PB‐201 was administered at a maximal dose of 100 mg per day showed significantly reduced HbA1c levels, which was comparable with the effects seen for sitagliptin. In addition to this, PB‐201 was also well tolerated, with mild to moderate adverse events (AEs), and no incidence of serious AEs 16 . Furthermore, a comprehensive quantitative pharmacological analysis of all clinical data related to PB‐201 locally and globally showed no effect of ethnic differences on PB‐201 exposure, supporting bridging offshore clinical study data.…”

“…In another later Phase 1 clinical study conducted in China to further explore the optimal dosage, the safety and efficacy of 50 mg/50 mg, 100 mg/50 mg and 100 mg/100 mg doses were studied in treatment‐naive patients with T2DM. The results showed good safety and tolerability in all dosage groups; PB‐201 decreased glycaemia levels in a dose‐dependent manner; the 100 mg/100 mg glucose control effect was significant, and safety was not significantly different from that reported in the lower dosage groups 16,17 …”

“…A total of 72% of the study participants reached the highest dose of 6 mg/d towards the end of the 6‐week dose‐escalation period. Thus, both clinical studies showed a dose‐dependent effect of PB‐201, with no reduction in efficacy even after long‐term usage 16,17 …”

“…Thus, both clinical studies showed a dose-dependent effect of PB-201, with no reduction in efficacy even after long-term usage. 16,17 In an early-phase dose-escalation study, a daily dose of 300 mg was determined to be the maximum tolerated dosage, and further Phase 1 and Phase 2 exploratory studies were conducted thereafter within the safe dosage range; 50 mg once daily was determined to be the lowest effective dosage for the product in a Phase 2 clinical study. Both these early dosage exploratory studies were based on patients with T2DM who were poorly controlled with metformin and received a daily dose of ≤100 mg, but after 12 weeks of treatment, the changes in HbA1c levels from baseline were significantly different and clinically significant compared to placebo after removing the placebo effect in the 100-mg oncedaily group.…”

“…The results showed good safety and tolerability in all dosage groups; PB-201 decreased glycaemia levels in a dose-dependent manner; the 100 mg/100 mg glucose control effect was significant, and safety was not significantly different from that reported in the lower dosage groups. 16,17 Here, we report the study design and rationale for a Phase 3 study consisting of three arms, with a placebo and active control design, assessing the efficacy and safety of PB-201 in treatment-naive T2DM patients from baseline to 24 weeks of double-blind treatment followed by a 28-week treatment extension period.…”