A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 6
- 主要终点
- Change in HbA1c in blood of patients for dapansutrile compared to placebo
研究概览
简要总结
The aim of the study is to determine whether NLRP3 inhibition with dapansutrile represents a new pharmacological option for diabetes management with potential as an anti-inflammatory agent to also address micro- and macro-vascular risk and complications from diabetes.
详细描述
To date, no other oral NLRP3 inhibitor has sufficiently advanced in development to be tested in a chronic low-grade inflammatory disease such as type 2 diabetes mellitus over a period of 3 to 4 months as proposed in this trial. Based on the publicly available information, dapansutrile is the most advanced oral NLRP3 inhibitor in development. The rationale is built upon dapansutrile's clinical and extensive preclinical and safety findings, and from data in chronic animal toxicology studies to date, which together enable and support its investigation in select chronic low-grade inflammatory diseases. Therefore, the investigators have selected type 2 diabetes mellitus and its complications, including risk for cardiovascular disease, as a disease with clinical features of low-grade inflammation to further investigate the therapeutic potential of NLRP3 inhibition with dapansutrile.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 2, Diabetes mellitus as defined by the criteria of the American Diabetes Association (ADA) Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (see Appendix 1) and recognized by the World Health Organization (WHO, 2019), for at least 3 months prior to the Baseline Visit/Day 1
- •HbA1c value of ≥ 7.7% to ≤ 11.0% at the Screening Visit.
- •High-sensitivity C-reactive protein (hsCRP) ≥ 1.5 mg/L at the Screening Visit.
- •Body mass index (BMI) ≥25 to ≤ 40 kg/m2 at the Screening Visit
- •Acceptable overall medical condition to safely participate in the study and complete all study procedures (particularly with regard to cardiovascular, renal, and hepatic conditions), in the opinion of the Investigator
排除标准
- •Diagnosis of type 1 diabetes mellitus
- •HbA1c value of ≤ 7.5% or ≥ 10.5% at the Baseline Visit/Day 1, as determined at point of care (local laboratory)
- •Use of thiazolidinediones (glitazones), pramlintide, or short-acting insulin/insulin analogues (as bolus or premixed insulin) within 12 weeks prior to the Screening Visit
- •Less than 80% compliance in taking investigational medicinal product by pill count during the Run-In Period, as assessed at the Baseline Visit/Day 1
- •Significant weight loss (> 5 kg) in the 12 weeks prior to the Screening Visit
- •Systolic blood pressure (BP) ≥ 160 mmHg, diastolic BP ≥ 100 mmHg, or resting heart rate (HR) ≥ 100 beats/minute at the Screening Visit
- •Previous myocardial infarction, any cardiac surgery
研究组 & 干预措施
Intervention Group
1000 mg dapansutrile (2 × 500mg tablets) administered twice a day from day 1 through the week 26 visit, inclusive. All tablets will be self-administered by mouth with water, with or without food.
干预措施: Dapansutrile (Drug)
Control Group
Matching placebo (2 tablets) administered twice a day from day 1 through the Week 26 visit, inclusive. All tablets will be self-administered by mouth with water, with or without food.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in HbA1c in blood of patients for dapansutrile compared to placebo
时间窗: two time assessment at baseline and week 26
Comparison of change in HbA1c for dapansutrile and placebo
次要结局
- Change in HbA1c in blood of patients for dapansutrile compared to placebo(six time assessment at baseline and week 4, 8, 12, 16, 20)
- Change in fasting plasma glucose for dapansutrile compared to placebo(seven time assessement at baseline and week 4, 8, 12, 16, 20, 26)
研究者
Marc Donath
Prof. Dr. med.
Kantonsspital Baden