Clinical Trial for the Investigational Drug (PB-201) in Subjects With Type 2 Diabetes Mellitus

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, 4-Period, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Three Dose Levels of the Investigational Drug (PB-201) in Drug-naive Adult Subjects With Type 2 Diabetes Mellitus as Monotherapy

This crossover study investigates the safety, tolerability, pharmacokinetics (PK) ,pharmacodynamics (PD) effect of three dose levels of PB-201,and characterizes the PK profile of a prominent des-methyl metabolite of PB-201(WI-0800), following dosing of three dose levels of PB-201 in drug-naive Chinese adult subjects with Type 2 diabetes mellitus (T2DM) as monotherapy. There were 7 days separating 4 treatment periods and at least 7-day washout (but not exceeding 14 days) between dosing in 4 periods with 3 dose levels of PB-201 and placebo. Three dose levels of PB-201 are: split dose regimen of 50 mg 30 minutes before morning meal plus 50 mg 30 minutes before lunch at approximately 3.5 hours after morning dose, and split dose regimen of 100 mg 30 minutes before morning meal plus 100 mg 30 minutes before lunch at approximately 3.5 hours after morning dose, and split dose regimen of 150 mg 30 minutes before morning meal plus 100 mg 30 minutes before lunch at approximately 3.5 hours after morning dose.

The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo

The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo

The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo

The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo

Inclusion Criteria: Glycosylated hemoglobin (HbA1c) 7.5%-11% at screening, and 7.0%-10.0% pre-randomization FPG 7.0 mmol/L-11.0mmol/L at screening and pre-randomization Body mass index (BMI) 18.5 and-35.0 kg/m2 at screening Antidiabetics-naive within 2 months before screening Exclusion Criteria: Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes History of febrile illness within 5 days prior to dosing Medical history of myocardial infarction, angina/unstable angina, coronary revascularization, stroke or transient ischemic attack Any medical history or current clinical evidence of congestive heart failure, New York Heart Association (NYHA) Functional Classification, Classes II-IV Episode(s) of hypoglycemia adverse events (HAE) of 'severe' intensity prior to screening; either: >1 in the previous 3 months; or >2 in the previous 6 months

Liu D, Du Y, Yao X, Wei Y, Zhu J, Cui C, Zhou H, Xu M, Li H, Ji L. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-naive Chinese patients with type 2 diabetes: a randomised controlled, crossover, single-centre phase 1 trial. EClinicalMedicine. 2021 Nov 6;42:101185. doi: 10.1016/j.eclinm.2021.101185. eCollection 2021 Dec.