Type2 Diabetes Mellitus
Conditions
Keywords
Glucokinase activator(GKA), hypoglycemia
Brief summary
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.
Interventions
DRUGglucokinase activator
PB-201 is a kind of dual and partial GKA
DRUGPlacebo
Placebo oral tablet
Sponsors
PegBio Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Glycosylated hemoglobin (HbA1c) 7.5%-11% at screening, and 7.0%-10.0% pre-randomization 2. FPG 7.0 mmol/L-11.0mmol/L at screening and pre-randomization 3. Body mass index (BMI) 18.5 and-35.0 kg/m2 at screening 4. Antidiabetics-naive within 2 months before screening
Exclusion criteria
1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes 2. History of febrile illness within 5 days prior to dosing 3. Medical history of myocardial infarction, angina/unstable angina, coronary revascularization, stroke or transient ischemic attack 4. Any medical history or current clinical evidence of congestive heart failure, New York Heart Association (NYHA) Functional Classification, Classes II-IV 5. Episode(s) of hypoglycemia adverse events (HAE) of 'severe' intensity prior to screening; either: 1. \>1 in the previous 3 months; or 2. \>2 in the previous 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to peak(Tmax) | 9 days | hour |
| Peak Plasma Concentration (Cmax) | 9 days | ng/mL |
| Area under the plasma concentration versus time curve (AUC) | 9 days | ng•hr/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change for fasting plasma glucose (FPG) | 8days | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo |
| The change for plasma insulin | 8 days | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo |
| The change for postprandial plasma glucose (PPG) | 8 days | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo |
| The change for plasma C-peptide | 8 days | The change from baseline value (day 0) to the last dose of drug in this period (day 7) compared to placebo |
Countries
China
Outcome results
None listed