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Dorzagliatin and 1st Phase Insulin and Beta-cell Glucose Sensitivity in IGT and NGT

Primary Purpose

Glucose Intolerance

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Dorzagliatin

Placebo

About this trial

This is an interventional treatment trial for Glucose Intolerance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Individuals aged ≥ 18 years but < 65years
Male or female
Body mass index of over 18 kg/m2 and < 30 kg/m2

Additional inclusion criteria for IGT group

Fasting plasma glucose <7.0 mmol/L and HbA1c < 6.5%
2 hour plasma glucose ≥7.8 and <11.1 mmol/L on 75g oral glucose tolerance test (OGTT)
Never been treated with glucose lowering drugs (including traditional Chinese medicine for glycemic control)

Additional inclusion criteria for NGT group

Fasting plasma glucose <5.6 mmol/L and HbA1c < 5.7%
2 hour plasma glucose <7.8 mmol/L on 75g oral glucose tolerance test (OGTT)
Never been treated with glucose lowering drugs (including traditional Chinese medicine for glycemic control

Exclusion Criteria:

Subjects who do not agree to participate in this study.
Country of birth is unknown.
Body weight less than 45kg.
Acute phase of cerebrovascular and cardiovascular diseases (within 6 months of recruitment).
Subjects with severe renal dysfunction as defined by eGFR <30 ml/min/1.73m2 or patients receiving renal dialysis (such as haemodialysis or continuous ambulatory peritoneal dialysis).
Severe hepatic dysfunction as defined by AST and/or ALT > 3 times upper limit of normal.
Severe cardiovascular disease, history of stroke, heart failure (NYHA III or IV) or history of myocardial infarction within last 12 months.
History of drug abuse or excessive alcohol intake based on investigator judgment.
History of diabetes mellitus.
Dehydration, diarrhoea or vomiting at the time of recruitment.
Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment.
Subjects with anaemia (Haemoglobin <11.0mg/dL or haematocrit <0.35 ) at screening, known iron deficiency, haemoglobinopathies or anaemia due to chronic disease.
Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.
Participation in a clinical trial with investigational product within 30 days before enrolment.
Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: ≥300 mL of blood within 30 days prior to study drug administration.
Subjects judged unsuitable for the study based on investigator judgment.
Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued.
Unwilling or unable to follow protocol requirements

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

dorzagliatin

placebo

Arm Description

Dorzagliatin 50 mg single dose

matching placebo

Outcomes

Primary Outcome Measures

2-hour hyperglycemic clamp

first phase insulin secretion

Secondary Outcome Measures

Full Information

NCT ID

NCT05468229

First Posted

July 19, 2022

Last Updated

July 21, 2022

Sponsor

Chinese University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT05468229

Brief Title

Dorzagliatin and 1st Phase Insulin and Beta-cell Glucose Sensitivity in IGT and NGT

Official Title

Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in Individuals With Impaired and Normal Glucose Tolerance

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

August 2022 (Anticipated)

Primary Completion Date

April 2023 (Anticipated)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Dorzagliatin, a novel dual allosteric activator of glucokinase. reduces blood glucose by increasing insulin secretion by enhancing sensitivity of beta cells to glucose. In this placebo controlled cross over study, we examined the effects of dorzagliatin in people with impaired glucose tolerance and normal glucose tolerance.

Detailed Description

Objective To investigate the acute effects of a single dose dorzagliatin on first phase insulin secretion and beta cell glucose sensitivity (βCGS) in individuals with impaired and normal glucose tolerance Methodology and rationale: A total of 20 subjects will be recruited, 10 in impaired glucose tolerant (IGT) and 10 in normal glucose tolerant (NGT) groups, respectively. Eligible participants will have a two-hour hyperglycemic clamp following a single dose of dorzagliatin or placebo in a randomized crossover fashion on V2 or V3. Subjects will be randomized to dorzagliatin 50mg or placebo in the IGT and NGT groups. Arterialized blood glucose (venous blood drawn from back of the hand placed in a temperature regulated box), measured every 5 minutes at the bedside Yellow Spring Instrument (YSI) or EKF glucose analyser, will be maintained at 12 mmol/l using an infusion of dextrose. Blood will be sampled for insulin and C-peptide at regular intervals for evaluation of first and second phase insulin secretion. Glucagon-like peptide-1 (GLP-1) and glucagon will be evaluated at regular intervals during the clamp studies. After 14 ± 2 days washout out (Day 14), participants will receive a single dose of dorzagliatin or matched placebo followed by a repeat hyperglycemic clamp to evaluate differences in beta-cell function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glucose Intolerance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Masking Description

double blind placebo controlled

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

dorzagliatin

Arm Type

Active Comparator

Arm Description

Dorzagliatin 50 mg single dose

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

matching placebo

Intervention Type

Drug

Intervention Name(s)

Dorzagliatin

Intervention Description

single oral dose of dorzagliatin 50 mg

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo

Primary Outcome Measure Information:

Title

2-hour hyperglycemic clamp

Description

first phase insulin secretion

Time Frame

2-hour

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Individuals aged ≥ 18 years but < 65years Male or female Body mass index of over 18 kg/m2 and < 30 kg/m2 Additional inclusion criteria for IGT group Fasting plasma glucose <7.0 mmol/L and HbA1c < 6.5% 2 hour plasma glucose ≥7.8 and <11.1 mmol/L on 75g oral glucose tolerance test (OGTT) Never been treated with glucose lowering drugs (including traditional Chinese medicine for glycemic control) Additional inclusion criteria for NGT group Fasting plasma glucose <5.6 mmol/L and HbA1c < 5.7% 2 hour plasma glucose <7.8 mmol/L on 75g oral glucose tolerance test (OGTT) Never been treated with glucose lowering drugs (including traditional Chinese medicine for glycemic control Exclusion Criteria: Subjects who do not agree to participate in this study. Country of birth is unknown. Body weight less than 45kg. Acute phase of cerebrovascular and cardiovascular diseases (within 6 months of recruitment). Subjects with severe renal dysfunction as defined by eGFR <30 ml/min/1.73m2 or patients receiving renal dialysis (such as haemodialysis or continuous ambulatory peritoneal dialysis). Severe hepatic dysfunction as defined by AST and/or ALT > 3 times upper limit of normal. Severe cardiovascular disease, history of stroke, heart failure (NYHA III or IV) or history of myocardial infarction within last 12 months. History of drug abuse or excessive alcohol intake based on investigator judgment. History of diabetes mellitus. Dehydration, diarrhoea or vomiting at the time of recruitment. Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment. Subjects with anaemia (Haemoglobin <11.0mg/dL or haematocrit <0.35 ) at screening, known iron deficiency, haemoglobinopathies or anaemia due to chronic disease. Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug. Participation in a clinical trial with investigational product within 30 days before enrolment. Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: ≥300 mL of blood within 30 days prior to study drug administration. Subjects judged unsuitable for the study based on investigator judgment. Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued. Unwilling or unable to follow protocol requirements

12. IPD Sharing Statement

Plan to Share IPD

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Dorzagliatin and 1st Phase Insulin and Beta-cell Glucose Sensitivity in IGT and NGT

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