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
Overview
- Phase
- Phase 1
- Intervention
- glucokinase activator
- Conditions
- Type2 Diabetes Mellitus
- Sponsor
- PegBio Co., Ltd.
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Time to peak(Tmax)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
PB-201 50/50mg by mouth,every morning and noon for 7 days
Intervention: glucokinase activator
PB-201 100/50mg by mouth,every morning and noon for 7 days
Intervention: glucokinase activator
PB-201 100/100mg by mouth,every morning and noon for 7 days
Intervention: glucokinase activator
placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Time to peak(Tmax)
Time Frame: 9 days
hour
Peak Plasma Concentration (Cmax)
Time Frame: 9 days
ng/mL
Area under the plasma concentration versus time curve (AUC)
Time Frame: 9 days
ng•hr/mL
Secondary Outcomes
- The change for plasma insulin(8 days)
- The change for fasting plasma glucose (FPG)(8days)
- The change for postprandial plasma glucose (PPG)(8 days)
- The change for plasma C-peptide(8 days)