A Trial to Evaluate the Effect of C21 on Endothelial Dysfunction in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is a single-centre, randomized, double-blind, placebo-controlled, 2-way cross-over phase 1b trial evaluating the pharmacodynamic effect of C21 on endothelial dysfunction and safety in subjects with type 2 diabetes mellitus (T2DM).

Official Title
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A Randomized, Double-blind, Placebo-controlled, 2-way Cross-over Trial Evaluating the Effect of C21 on Endothelial Dysfunction and Safety in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type2diabetes, Endothelial Dysfunction

Intervention / Treatment
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* Drug: C21


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient aged ≥ 40 years at the time of the screening visit (Visit 1). Documented diagnosed with T2DM prior to the screening visit (Visit 1). An RHI score ≤ 2 as assessed by EndoPAT at the time of the screening visit (Visit 1). Exclusion Criteria: Known, active hepatitis B, C, or human immunodeficiency virus (HIV) infection (i.e., HIV with a CD4 (cluster of differentiation 4) count <500 cells/mm³). Impaired hepatic function or clinically significant liver disease, which in the investigator's opinion makes the subject inappropriate for this trial. Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m2). Prolonged QTcF (QT interval with Fridericia's correction) (>450 ms), atrial fibrillation, clinically significant arrhythmia or other clinically significant abnormality in the resting ECG (electrocardiogram) at screening (Visit 1), as judged by the investigator. Unstable or deteriorating cardiac condition. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm 1<br>A single dose of C21 at visit 2 followed by a single dose of placebo at visit 3. | Drug: C21<br>* C21 is an angiotensin II type 2 receptor agonist (ATRAG)<br>|
| Experimental: Treatment arm 2<br>A single dose of placebo at visit 2 followed by a single dose C21 at visit 3. | Drug: C21<br>* C21 is an angiotensin II type 2 receptor agonist (ATRAG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic effect | Reactive hyperemia index (RHI) score as measured by EndoPAT (Endothelial pulse amplitude tonometry (PAT)). Normal value: RHI > 1.67. Abnormal value: RHI ≤ 1.67. A lower RHI score following C21 compared to placebo is the desired outcome. | Maximum 15 days after first Investigational Medical Product (IMP) intake. |