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Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia

Phase 2
Recruiting
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: Placebo
Registration Number
NCT06047262
Lead Sponsor
University Hospital, Basel, Switzerland
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
300
Inclusion Criteria
  • 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) ≥18 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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intervention GroupDapansutrile1000 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.
Control GroupPlaceboMatching 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.
Primary Outcome Measures
NameTimeMethod
Change in HbA1c in blood of patients for dapansutrile compared to placebotwo time assessment at baseline and week 26

Comparison of change in HbA1c for dapansutrile and placebo

Secondary Outcome Measures
NameTimeMethod
Change in HbA1c in blood of patients for dapansutrile compared to placebosix time assessment at baseline and week 4, 8, 12, 16, 20

Comparison of change in HbA1c for dapansutrile and placebo

Change in fasting plasma glucose for dapansutrile compared to placeboseven time assessement at baseline and week 4, 8, 12, 16, 20, 26

Comparison of change in fasting plasma glucose for dapansutrile and placebo

Trial Locations

Locations (1)

University Hospital Basel

🇨🇭

Basel, Switzerland

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