NCT03973515

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2019

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 29, 2019

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 4, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

August 27, 2019

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2019

Completed
Last Updated

January 22, 2020

Status Verified

June 1, 2019

Enrollment Period

4 months

First QC Date

May 29, 2019

Last Update Submit

January 21, 2020

Conditions

Type2 Diabetes Mellitus

Keywords

Glucokinase activator(GKA)hypoglycemia

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (4)

  • 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

  • The change for plasma insulin

    8 days

Study Arms (4)

PB-201 50/50mg by mouth,every morning and noon for 7 days

EXPERIMENTAL
Drug: glucokinase activator

PB-201 100/50mg by mouth,every morning and noon for 7 days

EXPERIMENTAL
Drug: glucokinase activator

PB-201 100/100mg by mouth,every morning and noon for 7 days

EXPERIMENTAL
Drug: glucokinase activator

placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

glucokinase activatorDRUG

PB-201 is a kind of dual and partial GKA

Also known as: PB-201
PB-201 100/100mg by mouth,every morning and noon for 7 daysPB-201 100/50mg by mouth,every morning and noon for 7 daysPB-201 50/50mg by mouth,every morning and noon for 7 days
PlaceboDRUG

Placebo oral tablet

Also known as: PB-201 Placebo
placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Peking University Third Hospital

Beijing, China

Location

Related Publications (1)

  • 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.

    PMID: 34805810DERIVED

MeSH Terms

Conditions

Hypoglycemia

Interventions

glucokinase activator compound 50Lead-201

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • HaiYan Li

    Peking University Third Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 29, 2019

First Posted

June 4, 2019

Study Start

August 27, 2019

Primary Completion

December 19, 2019

Study Completion

December 19, 2019

Last Updated

January 22, 2020

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)