Effect of C21 on Forearm Blood Flow

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of C21 on forearm blood flow by use of strain-gauge venous occlusion plethysmography.

Detailed Description
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Subject will be screened for eligibility. Eligible subjects will receive ascending doses of C21 (3, 10, 30 and 100 µg/min through locla i.a. infusions for 5 min/dose. Forearm blood flow measurements will be performed in both arms during the last 2 minutes of each dose. infusions of sodium nitroprusside will be performed as a positive control using the same methodology.

Official Title
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A Phase 1, Open-label, Single-centre Study Investigating the Effect of C21 on Forearm Blood Flow in Healthy Male Subjects by Use of Strain-gauge Venous Occlusion Plethysmography

Conditions
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Study Vasodilatory Effects of C21

Intervention / Treatment
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* Drug: C21
* Drug: Sodium Nitroprusside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give written informed consent for participation in the study and to comply with study requirements. Healthy male subject aged 18-45 years Body mass index ≥ 18.5 and ≤ 30.0 kg/m2. Wlling to use condom or be vasectomised or practice sexual abstinence Clinically normal medical history, physical findings, vital signs, ECG and laboratory values Exclusion Criteria: History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. History of thrombotic disease, vascular disorder, or severe bleeding disease. Poor brachial artery access. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of baseline Malignancy within the past 5 years with the exception of basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Any planned major surgery within the duration of the study. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV). Abnormal vital signs Prolonged QT interval, cardiac arrhythmias or any clinically significant abnormalities in the resting ECG History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to the IMPs, including any of the excipients of the IMPs. Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins, and minerals Regular use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid Vaccination within 1 week prior to dosing or plans to receive any vaccine during the study conduct. Planned treatment or treatment with another investigational drug within 3 months Current regular smokers or users of nicotine products. History of alcohol abuse Presence or history of drug abuse Positive screen for drugs of abuse or alcohol at screening History of, or current use of, anabolic steroids. Inability to refrain from consuming caffeine-containing beverages during Day 1 Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the 3 months prior to screening. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects will receive increasing doses of C21
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C21<br>15 µg C21 (infusion rate 3 µg/min) 50 µg C21 (infusion rate 10 µg/min) 150 µg C21 (infusion rate 30 µg/min) 500 µg C21 (infusion rate 100 µg/min) 1000 µg C21 (infusion rate 200 µg/min) | Drug: C21<br>* C21 in ascending doses of 15, 50, 150, 500 and 1000 µg<br>* Other names: Compund 21;|
| Experimental: Control group<br>4 µg nitroprusside (infusion rate 0.8 µg/min) 8 µg nitroprusside (infusion rate 1.6 µg/min) 16 µg nitroprusside (infusion rate 3.2 µg/min) | Drug: Sodium Nitroprusside<br>* Ascending doses of 4, 8 and 16 µg<br>* Other names: Nipruss;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in forearm blood flow in response to increasing intraarterial doses of C21 |  | 85 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in forearm blood flow in response to increasing intra arterial doses of sodium nitroprusside |  | 45 minutes | 
| Frequency of adverse events |  | Day 7 | 
| Intensity of adverse events |  | Day 7 | 
| Seriousness of adverse events |  | Day 7 | 
| Clinically significant changes in vital sign parameters |  | 5 hours | 
| Clinically significant changes in ECG parameters |  | 5 hours | 
| Clinically significant changes in safety laboratory parameters |  | 5 hours |