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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dapansutrile
  Patients receive investigational product.
• Препарат Placebo
  Patients receive placebo.

Первичные конечные точки

• Change in HbA1c in blood of patients for dapansutrile compared to placebo [Срок оценки: two time assessment at baseline and week 26]

Вторичные конечные точки (2)

• Change in HbA1c in blood of patients for dapansutrile compared to placebo [Срок оценки: six time assessment at baseline and week 4, 8, 12, 16, 20]
• Change in fasting plasma glucose for dapansutrile compared to placebo [Срок оценки: seven time assessement at baseline and week 4, 8, 12, 16, 20, 26]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 2 центра

• Hopital Lariboisiere — Paris
• Hopital Bichat — Paris

Швейцария · 2 центра

• University Hospital Basel — Basel
• Kantonsspital Olten — Olten

Бельгия · 1 центр

• CHU de Liege — Liège

Германия · 1 центр

• Deutsches Zentrum für Diabetesforschung Düsseldorf — Düsseldorf

Идентификаторы

NCT: NCT06047262 · 2023-01387; kt23Donath

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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