Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in Individuals With Recent-onset Type 2 Diabetes and Monogenic Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- first phase insulin response to glucose
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 recent-onset T2D group
- •Diagnosis of T2D for at least 3 months and less than 2 years
- •On diet control only
- •HbA1c>6.5 % and <8% Additional Inclusion criteria for GK MODY-2 group
- •Abnormal fasting plasma glucose >5.6 mmol/l and known heterozygous carrier of pathogenic GK mutation
排除标准
- •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
- •Severe hypoglycaemia resulting in seizure/unconsciousness/coma/hospitalization in the last 3 months before screening
- •Diagnosis with Type 1 Diabetes Mellitus (T1DM) or any previous episodes of diabetic ketoacidosis.
- •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 <9.0mg/dL)
- •Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.
- •Participation in a clinical trial 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 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.
- •Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued
- •Unwilling or unable to follow protocol requirements.
研究组 & 干预措施
Group 1
receive a single oral dose of dorzagliatin 75mg tablet on visit 2 and receive one placebo tablet on visit 3
干预措施: Dorzagliatin (Drug)
Group 1
receive a single oral dose of dorzagliatin 75mg tablet on visit 2 and receive one placebo tablet on visit 3
干预措施: placebo (Drug)
Group 2
receive a single oral dose of one placebo tablet on visit 2 and receive dorzagliatin 75mg tablet on visit 3
干预措施: Dorzagliatin (Drug)
Group 2
receive a single oral dose of one placebo tablet on visit 2 and receive dorzagliatin 75mg tablet on visit 3
干预措施: placebo (Drug)
结局指标
主要结局
first phase insulin response to glucose
时间窗: 10 mins
measure insulin between 0 to 10 minutes
次要结局
- First phase C-peptide responses to glucose(10 mins)
- Maximum concentration (Cmax) 1st phase insulin between 0 to 10 minutes(10 mins)
- Time to maximum (Tmax) of acute phase insulin response between 0 to 10 minutes(10 mins)
- Second phase insulin response(40 mins)
- Beta cell glucose sensitivity(40 mins)
- Insulin sensitivity index(40 mins)
- Area under curve of glucagon levels(120 mins)
- Area under curve of GLP-1 levels(120 mins)
研究者
Juliana Chan
Professor
Chinese University of Hong Kong