Chronic Dorzagliatin on Insulin and Incretin Function in Intermediate Hyperglycemia and Type 2 Diabetes

Effects of Repeated Dose of Dorzagliatin on Insulin Secretion, Glucagon Release and Incretin Function in Intermediate Hyperglycemia and Type 2 Diabetes

A total of 30 subjects will be recruited 15 with intermediate hyperglycemia and 15 in the tyep 2 diabetes group respectively. Eligible participants will undergo hyperglycemic-clamp/oral glucose tolerance at baseline and after 4 weeks of dorzagliatin treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus; Prediabetes / Type 2 Diabetes
• Intervention / Treatment: Drug: Dorzagliatin

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elaine Chow; Phone Number: +852 35051641; Email: e.chow@cuhk.edu.hk
• Study Contact Backup: Name: Elaine Chow; Phone Number: +852 35051642

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Phase 1 Clinical Trial Centre
    • Contact: Michelle Wong; Phone Number: +852 35051641; Email: michellewong27@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individuals aged ≥ 18 years but < 70 years
2. Male or female
3. Body mass index of over 18 kg/m2 and < 35 kg/m2

Additional inclusion criteria for IH group

• Fasting plasma glucose <7.0 mmol/L and HbA1c < 6.5%
• 1 hour plasma glucose ≥8.6 and <11.6 mmol/L on 75g oral glucose tolerance test (OGTT)
• No use of glucose lowering drugs in past 6 months

Additional inclusion criteria for T2D group

• HbA1c 6.5 to 10% at screening
• On diet control, or stable dose of oral glucose lowering drugs metformin for at least 8 weeks

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 aspartate aminotransferase (AST) and/or alanine aminotransferase (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. Dehydration, diarrhoea or vomiting at the time of recruitment. 10. Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment.

  11. Subjects with anaemia (Haemoglobin <9.0mg/dL). 12. Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.

  13. Participation in a clinical trial with investigational product within 30 days before enrolment.

  14. 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.

  15. Subjects judged unsuitable for the study based on investigator judgment. 16. Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued.

  17. Unwilling or unable to follow protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IH/T2D; partipiants with intermediate hyperglycemia (IH) n=15 or T2D (n=15)	Drug: Dorzagliatin; chronic treatment with dorzagliatin for 4 weeks (50mg twice daily or 75mg twice daily, oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Insulin secretion	Acute (first phase) insulin response (AIRg) to glucose will be calculated as the mean incremental responses above baseline (average of -20 and -10 and 0 minutes) to the samples drawn at 2, 4, 6, 8 and 10 minutes of the hyperglycemic clamp.	At baseline and after 4 weeks of study drug treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Second phase insulin secretion	The mean incremental insulin levels between 60 to 90 minutes of hyperglycemic clamp	At baseline and after 4 weeks of study drug treatment
Beta cell glucose sensitivity	Beta cell glucose sensitivity will be calculated as increment of insulin secretion in 60-90 minutes of the clamp minus basal insulin divided by glucose change in the same period	At baseline and after 4 weeks of study drug treatment
Glucagon-like peptide -1 (GLP-1)	GLP-1 secretion Area under the curve (0-270 minute during hyperglyemic- OGTT clamp study)	At baseline and after 4 weeks of study drug treatment
Glucagon	Glucagon area under the curve (0-270 minute) during hyperglyemic- OGTT clamp	At baseline and after 4 weeks of study drug treatment
Incretin effect	Difference between the post prandial (100-270min) and preprandial (60-90min) C peptide response	At baseline and after 4 weeks of study drug treatment

Collaborators and Investigators

• Sponsor: Elaine Chow
• Investigators: Principal Investigator: Elaine Chow, MBChB, PhD, FRCP, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): April 2, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 1, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: diabetes; clamp; glucokinase activator
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Hyperglycemia
• Other Study ID Numbers: SENSITISE-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No