Clinical trial NCT03973515: Clinical Trial for the Investigational Drug (PB-201) in Subjects With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type2 Diabetes Mellitus
Keywords: Glucokinase activator(GKA)
hypoglycemia
Lead sponsor: PegBio Co., Ltd.
Sponsor class: OTHER
First posted: 2019-06-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to peak(Tmax)
timeFrame: 9 days
measure: Peak Plasma Concentration (Cmax)
timeFrame: 9 days
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 9 days
Secondary outcomes:
measure: The change for fasting plasma glucose (FPG)
timeFrame: 8days
measure: The change for postprandial plasma glucose (PPG)
timeFrame: 8 days
measure: The change for plasma C-peptide
timeFrame: 8 days
measure: The change for plasma insulin
timeFrame: 8 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
Study officials:
affiliation: Peking University Third Hospital
name: HaiYan Li
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.