Thrombosis
Conditions
Keywords
tissue-plasminogen activator (t-PA), plasminogen-activator inhibitor 1 (PAI-1), fibrinolysis, thrombosis
Brief summary
SAD study: Eighteen subjects will be included in the SAD study (single dose) in 3 parallel arms, each with 6 subjects. The 3 arms will receive a single dose of one of the CS1 formulations I, II or III. The result of the pharmacokinetics analysis from the 6 first subjects is defined as SAD Pilot and will be used to evaluate the timing of PK sampling. Based on pharmacokinetic evaluations from all 18 subjects one of the formulations I (275 mg), II (276 mg) or III (276 mg) will be chosen to proceed into the MAD study. If none of the formulations show the desired PK properties the formulations may be re-dosed with a slightly different timing of the dose, i.e the IMP to be administered earlier or later during the evening. MAD study: Fifteen subjects will be included in a dose escalating study with 2 dose levels. The subjects will receive the lowest dose level (275 or 276 mg depending on the outcome of SAD) for the first 2 weeks before the dose is doubled (550 or 552 mg depending on the outcome of SAD) for the following 2 weeks.
Interventions
DRUGCS1-Sodium Valproate
Single and multiple dose evaluation of CS1
Sponsors
Cereno Scientific AB
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Safety, pharmacokinetics and pharmacodynamics of CS1
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willing and able to give written informed consent for participation in the study 2. Male and female subjects age ≥ 40 years, ≤ 75 years inclusive. 3. BMI 27- 35 kg/m2 4. PAI-1 levels minimum 15 kIE/L (applies only to the MAD study) 5. Acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator. Subjects with stable hypertension with one or more antihypertensive drugs can be accepted as acceptable medical history. 6. Male subjects who has not documented a vasectomy, must be willing to use condom from the date of dosing until three months after dosing of the IMP to prevent drug exposure of a partner and refrain from donating sperm and if they have a fertile partner, she must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy . 7. The females must be of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 months of amenorrhea (simultaneous determination of follicle stimulating hormone 25-140 IU/l and estradiol \< 200 pmol/l is confirmatory) -
Exclusion criteria
Diagnosis and main eligibility criteria Inclusion criteria: 1. Willing and able to give written informed consent for participation in the study 2. Male and female subjects age ≥ 40 years, ≤ 75 years inclusive. 3. BMI 27- 35 kg/m2 4. PAI-1 levels minimum 15 kIE/L (applies only to the MAD study) 5. Acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator. Subjects with stable hypertension with one or more antihypertensive drugs can be accepted as acceptable medical history. 6. Male subjects who has not documented a vasectomy, must be willing to use condom from the date of dosing until three months after dosing of the IMP to prevent drug exposure of a partner and refrain from donating sperm and if they have a fertile partner, she must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy . 7. The females must be of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 months of amenorrhea (simultaneous determination of follicle stimulating hormone 25-140 IU/l and estradiol \< 200 pmol/l is confirmatory)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic of CS1 in plasma | up to four weeks | Plasma concentration of Valproate in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | up to four weeks | Adverse event recording in free text |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in hs-CRP levels | four weeks | mg/L |
| Change in platelet numbers | four weeks | number of platelets per microliter blood |
| change in bleeding time | four weeks | Differences in bleeding time (minutes) |
| Change in PAP | four weeks | ng/ml |
| Change in fibrinogen levels | four weeks | g/L |
| Change in plasma PAI-1 levels | four weeks | ng/mL |
Countries
Sweden
Outcome results
None listed