Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGDapansutrile
Patients receive investigational product.
DRUGPlacebo
Patients receive placebo.
Sponsors
Marc Donath
European Union (Horizon Europe Programme)
State Secretariat for Education Research and Innovation, Switzerland
Olatec Therapeutics LLC
Departement Klinische Forschung Universität Basel
CTU Kantonsspital Baden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-blind
Intervention model description
randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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) ≥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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c in blood of patients for dapansutrile compared to placebo | two time assessment at baseline and week 26 | Comparison of change in HbA1c for dapansutrile and placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c in blood of patients for dapansutrile compared to placebo | six 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 placebo | seven time assessement at baseline and week 4, 8, 12, 16, 20, 26 | Comparison of change in fasting plasma glucose for dapansutrile and placebo |
Countries
Belgium, France, Germany, Switzerland
Contacts
CONTACTMarc Y. Donath, Prof.
CONTACTMarkus Veit
STUDY_CHAIRMarc Y. Donath, Prof.
Kantonsspital Baden, Switzerland
Outcome results
None listed