Study Vasodilatory Effects of C21
Conditions
Brief summary
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
Subject will be screened for eligibility. Eligible subjects will receive ascending doses of C21 (3, 10, 30, 100, and 200 µg/min through local intra-arterial 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.
Interventions
DRUGC21
C21 in ascending doses of 15, 50, 150, 500 and 1000 µg
DRUGSodium Nitroprusside
Ascending doses of 4, 8 and 16 µg sodium nitroprusside Positive control
Sponsors
CTC Clinical Trial Consultants AB
Vicore Pharma AB
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Subjects will receive increasing doses of C21
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willing and able to give written informed consent for participation in the study and to comply with study requirements. 2. Healthy male subject aged 18-45 years 3. Body mass index ≥ 18.5 and ≤ 30.0 kg/m2. 4. Wlling to use condom or be vasectomised or practice sexual abstinence 5. Clinically normal medical history, physical findings, vital signs, ECG and laboratory values
Exclusion criteria
1. 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. 2. History of thrombotic disease, vascular disorder, or severe bleeding disease. 3. Poor brachial artery access. 4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of baseline 5. 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. 6. Any planned major surgery within the duration of the study. 7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV). 8. Abnormal vital signs 9. Prolonged QT interval, cardiac arrhythmias or any clinically significant abnormalities in the resting ECG 10. 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. 11. Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins, and minerals 12. Regular use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid 13. Vaccination within 1 week prior to dosing or plans to receive any vaccine during the study conduct. 14. Planned treatment or treatment with another investigational drug within 3 months 15. Current regular smokers or users of nicotine products. 16. History of alcohol abuse 17. Presence or history of drug abuse 18. Positive screen for drugs of abuse or alcohol at screening 19. History of, or current use of, anabolic steroids. 20. Inability to refrain from consuming caffeine-containing beverages during Day 1 21. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the 3 months prior to screening. 22. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 85 minutes | Percentage change from baseline in forearm blood flow (FBF) in response to increasing intraarterial doses of C21 (3, 10, 30, 100, and 200 μg/min) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intra-arterial Doses of Sodium Nitroprusside | 45 minutes | Percentage change from baseline in forearm blood flow in response to increasing intra-arterial doses of sodium nitroprusside (0.8, 1.6, and 3.2 μg/min) |
| Frequency of Adverse Events | Day 1-7 | Total number of adverse events was counted |
| Number of Mild, Moderate, and Severe Adverse Events | Day 1-7 | Number of mild, moderate, and severe adverse events was counted |
| Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 85 min | Geometric mean forearm blood flow (mL/min) by increasing C21 dose (3, 10, 30, 100, and 200 μg/min) |
| Number of Participants With Clinically Significant Changes in Vital Sign Parameters | 5 hours | Participants with Clinically significant changes from baseline (screening ) to the end of treatment in mean systolic blood pressure, diastolic blood pressure or pulse rate were counted |
| Number of Participants With Clinically Significant Changes in ECG Parameters | 5 hours | Participants with Clinically significant changes from baseline (screening ) to the end of treatment in mean values of the ECG parameters were counted |
| Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters | 5 hours | Participants with Clinically significant changes from baseline (screening ) to the end of treatment (Day 1) in mean clinical chemistry, haematology or coagulation parameters were counted |
| Number of Serious Adverse Events (SAEs) | Day 1-7 | Number of serious adverse events (SAEs) was counted |
Countries
Sweden
Participant flow
Pre-assignment details
5 subjects were enrolled into the trial and all subjects received 5 ascending doses of C21 followed by 3 ascending doses of sodium nitroprusside as a positive control. Thus, the 5 subjects were reused for both C21 and sodium nitroprusside treatment.
Participants by arm
| Arm | Count |
|---|---|
| C21 Combined 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)
C21: C21 in ascending doses of 15, 50, 150, 500 and 1000 µg | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | C21 Combined |
|---|---|
| Age, Continuous | 29.0 years STANDARD_DEVIATION 9.2 |
| Body mass index | 26.8 kg/m2 STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 180.0 cm STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 86.8 kg STANDARD_DEVIATION 9.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21
Percentage change from baseline in forearm blood flow (FBF) in response to increasing intraarterial doses of C21 (3, 10, 30, 100, and 200 μg/min)
Time frame: 85 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C21 3 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 27.8 percentage of change from baseline | Standard Deviation 24.3 |
| C21 10 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 17.2 percentage of change from baseline | Standard Deviation 5.5 |
| C21 30 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 37.0 percentage of change from baseline | Standard Deviation 26.6 |
| C21 100 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 28.5 percentage of change from baseline | Standard Deviation 22.7 |
| C21 200 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intraarterial Doses of C21 | 60.5 percentage of change from baseline | Standard Deviation 38.3 |
Secondary
Dose-response Curve of C21 on Forearm Blood Flow (FBF)
Geometric mean forearm blood flow (mL/min) by increasing C21 dose (3, 10, 30, 100, and 200 μg/min)
Time frame: 85 min
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| C21 3 ug/Min | Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 2.594 mL/min | Geometric Coefficient of Variation 43.2 |
| C21 10 ug/Min | Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 2.594 mL/min | Geometric Coefficient of Variation 32.4 |
| C21 30 ug/Min | Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 3.231 mL/min | Geometric Coefficient of Variation 44.7 |
| C21 100 ug/Min | Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 3.215 mL/min | Geometric Coefficient of Variation 38.1 |
| C21 200 ug/Min | Dose-response Curve of C21 on Forearm Blood Flow (FBF) | 3.907 mL/min | Geometric Coefficient of Variation 24.5 |
95% CI: [0.8313, 1.2025]
95% CI: [1.0355, 1.4979]
95% CI: [1.0304, 1.4904]
95% CI: [1.0305, 1.4906]
95% CI: [0.8273, 1.1967]
95% CI: [1.252, 1.811]
95% CI: [1.2522, 1.8113]
95% CI: [1.0053, 1.4541]
95% CI: [1.0103, 1.4614]
95% CI: [1.0357, 1.4981]
Secondary
Frequency of Adverse Events
Total number of adverse events was counted
Time frame: Day 1-7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C21 3 ug/Min | Frequency of Adverse Events | 3 Number of adverse events |
| C21 10 ug/Min | Frequency of Adverse Events | 3 Number of adverse events |
Secondary
Number of Mild, Moderate, and Severe Adverse Events
Number of mild, moderate, and severe adverse events was counted
Time frame: Day 1-7
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C21 3 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of mild AEs | 3 Number of events |
| C21 3 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of moderate Aes | 0 Number of events |
| C21 3 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of severe AEs | 0 Number of events |
| C21 10 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of mild AEs | 3 Number of events |
| C21 10 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of moderate Aes | 0 Number of events |
| C21 10 ug/Min | Number of Mild, Moderate, and Severe Adverse Events | Number of severe AEs | 0 Number of events |
Secondary
Number of Participants With Clinically Significant Changes in ECG Parameters
Participants with Clinically significant changes from baseline (screening ) to the end of treatment in mean values of the ECG parameters were counted
Time frame: 5 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 3 ug/Min | Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| C21 10 ug/Min | Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters
Participants with Clinically significant changes from baseline (screening ) to the end of treatment (Day 1) in mean clinical chemistry, haematology or coagulation parameters were counted
Time frame: 5 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 3 ug/Min | Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters | 0 Participants |
| C21 10 ug/Min | Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Sign Parameters
Participants with Clinically significant changes from baseline (screening ) to the end of treatment in mean systolic blood pressure, diastolic blood pressure or pulse rate were counted
Time frame: 5 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| C21 3 ug/Min | Number of Participants With Clinically Significant Changes in Vital Sign Parameters | 0 Participants |
| C21 10 ug/Min | Number of Participants With Clinically Significant Changes in Vital Sign Parameters | 0 Participants |
Secondary
Number of Serious Adverse Events (SAEs)
Number of serious adverse events (SAEs) was counted
Time frame: Day 1-7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C21 3 ug/Min | Number of Serious Adverse Events (SAEs) | 0 Number of SAEs |
| C21 10 ug/Min | Number of Serious Adverse Events (SAEs) | 0 Number of SAEs |
Secondary
Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intra-arterial Doses of Sodium Nitroprusside
Percentage change from baseline in forearm blood flow in response to increasing intra-arterial doses of sodium nitroprusside (0.8, 1.6, and 3.2 μg/min)
Time frame: 45 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C21 3 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intra-arterial Doses of Sodium Nitroprusside | 319.8 percentage of change from baseline | Standard Deviation 186 |
| C21 10 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intra-arterial Doses of Sodium Nitroprusside | 229.5 percentage of change from baseline | Standard Deviation 73.1 |
| C21 30 ug/Min | Percentage Change From Baseline in Forearm Blood Flow in Response to Increasing Intra-arterial Doses of Sodium Nitroprusside | 319.6 percentage of change from baseline | Standard Deviation 141.4 |