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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Drug: glucokinase activator
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PB-201 50/50mg by mouth,every morning and noon for 7 days<br> | Drug: glucokinase activator<br>* PB-201 is a kind of dual and partial GKA<br>* Other names: PB-201;|
| Experimental: PB-201 100/50mg by mouth,every morning and noon for 7 days<br> | Drug: glucokinase activator<br>* PB-201 is a kind of dual and partial GKA<br>* Other names: PB-201;|
| Experimental: PB-201 100/100mg by mouth,every morning and noon for 7 days<br> | Drug: glucokinase activator<br>* PB-201 is a kind of dual and partial GKA<br>* Other names: PB-201;|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Placebo oral tablet<br>* Other names: PB-201 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to peak(Tmax) | hour | 9 days | 
| Peak Plasma Concentration (Cmax) | ng/mL | 9 days | 
| Area under the plasma concentration versus time curve (AUC) | ng•hr/mL | 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change for fasting plasma glucose (FPG) | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo | 8days | 
| The change for postprandial plasma glucose (PPG) | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo | 8 days | 
| The change for plasma C-peptide | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo | 8 days | 
| The change for plasma insulin | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucokinase activator(GKA), hypoglycemia