Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes

NCT ID: NCT04531631

Last Updated: 2022-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2022-02-15

Brief Summary

Diabetes is a disorder of energy energy metabolism. Glucose is the main energy substrate for generation of ATP to maintain cellular metabolism, structure and function. Glucokinase (GK) serves as a glucose sensor for the initiation of the energy generation.for energy metabolism. Dorzagliatin is a novel, first-in-class, dual-acting allosteric GK activator (GKA). It increases the affinity of GK for glucose by directly binding a pocket distal to its active site, thus lowering the set point for glucose-stimulated insulin secretion in the beta-cell.

Dorzagliatin is a new drug which acts as GK sensor activator (GKA). It can restore the sensitivity of the pancreas cells to glucose and improve glucose control. The drug has been trialled in healthy volunteers and in individuals with type 2 diabetes.

The aim of this study is to understand the way in which dorzagliatin works to improve blood sugar control in people with diabetes. The study will look at how dorzagliatin affects insulin secretion and the sensitivity of the pancreas to changes in blood sugar levels. We will examine whether dorzagliatin can restore the function of this GK sensor in patients with known mutations. In a cross-over study, we will evaluate the effects of dorzagliatin, a specific GKA versus placebo in terms of insulin secretion and beta-cell glucose sensitivity in patients with newly-diagnosed T2D and patients who are known heterozygous carriers of GK mutations.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Group 1

receive a single oral dose of dorzagliatin 75mg tablet on visit 2 and receive one placebo tablet on visit 3

Group Type: OTHER

Dorzagliatin

Intervention Type: DRUG

tablet

placebo

Intervention Type: DRUG

placebo

Group 2

receive a single oral dose of one placebo tablet on visit 2 and receive dorzagliatin 75mg tablet on visit 3

Group Type: OTHER

Dorzagliatin

Intervention Type: DRUG

tablet

placebo

Intervention Type: DRUG

placebo

Interventions

Dorzagliatin

tablet

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Individuals aged ≥ 18 years but < 65years

2. Male or female

• Diagnosis of T2D for at least 3 months and less than 2 years
• On diet control only
• Abnormal fasting plasma glucose >5.6 mmol/l and known heterozygous carrier of pathogenic GK mutation

Exclusion Criteria

1. Subjects who do not agree to participate in this study.

2. Country of birth is unknown

3. Body weight less than 45kg

4. Acute phase of cerebrovascular and cardiovascular diseases (within 6 months of recruitment).

5. 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).

6. Severe hepatic dysfunction as defined by AST and/or ALT > 3 times upper limit of normal

7. Severe cardiovascular disease, history of stroke, heart failure (NYHA III or IV) or history of myocardial infarction within last 12 months

8. History of drug abuse or excessive alcohol intake based on investigator judgment

9. Severe hypoglycaemia resulting in seizure/unconsciousness/coma/hospitalization in the last 3 months before screening

10. Diagnosis with Type 1 Diabetes Mellitus (T1DM) or any previous episodes of diabetic ketoacidosis.

11. Dehydration, diarrhoea or vomiting at the time of recruitment

12. Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment

13. Subjects with anaemia (Haemoglobin <9.0mg/dL)

14. Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.

15. Participation in a clinical trial within 30 days before enrolment

16. 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.

17. Subjects judged unsuitable for the study based on investigator judgment

18. Use of metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 [GLP-1] agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 3 months prior to study enrolment will not be permitted.

19. Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued

20. Unwilling or unable to follow protocol requirements.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Juliana Chan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Chinese University of Hong Kong

Hong Kong, , Hong Kong

Countries

Hong Kong

Other Identifiers

CRE-2020.196

Identifier Type: -

Identifier Source: org_study_id