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

Phase 1

Completed

Brief Summary: 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).

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Treatment arm 2	C21	A single dose of placebo at visit 2 followed by a single dose C21 at visit 3.
Treatment arm 1	C21	A single dose of C21 at visit 2 followed by a single dose of placebo at visit 3.

Primary Outcome Measures

Name	Time	Method
Pharmacodynamic Effect	Maximum 15 days after first Investigational Medical Product (IMP) intake.	Reactive hyperemia index (RHI) score as measured by EndoPAT (Endothelial pulse amplitude tonometry (PAT)). The EndoPAT software, provided with the device, is calculating the RHI using a computerised, automated algorithm. Reactive Hyperemia Index (RHI) score is a post-to-pre occlusion pulse amplitude tonometry signal ratio in the occluded arm relative to the same ratio in the control arm, and corrected for baseline vascular tone. RHI is a measure of endothelial function. Normal value: RHI \> 1.67. Abnormal value: RHI ≤ 1.67. There is no theoretical minimum and/or maximum values for the RHI score. A lower RHI score following C21 compared to placebo is the desired outcome.

Secondary Outcome Measures

Name	Time	Method
Augmentation Index (AI) Score as Measured by EndoPAT (Endothelial Pulse Amplitude Tonometry (PAT)). The AI Score Reported is Change Between Baseline Value and Value at the Visit Where Either C21 or Placebo is Taken.	Maximum 15 days after first Investigational Medical Product (IMP) intake.	The EndoPAT software, provided with the device is calculating the the Augmentation index (AI) using a computerised, automated algorithm. Augmentation index is a measurement of vascular stiffness. Augmentation index is calculated from PAT pulses based on the following formula AIx = 100 × (Augmentation pressure)/(Pulse Pressure). Ideally the augmentation index is somewhere between 20-80, but can be both negative and positive depending on the value of the augmentation pressure. A higher value is indicative of vascular stiffness.