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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: glucokinase activator

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2019
• Primary Completion (Actual): December 19, 2019
• Study Completion (Actual): December 19, 2019

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: June 2, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: hypoglycemia; Glucokinase activator(GKA)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: PB-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No