Study Investigation Pharmacokinetics and Pharmacodynamics of CS1

Thrombosis Clinical Trial

Official title:

A Single Center, Randomised Study to Investigate Pharmacokinetics of CS1, Safety and Tolerability and in Obese, Borderline Hypertensive But Otherwise Healthy and Medicine Free Subjects After Administration of Single and Multiple Doses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03903302
• Other study ID #: CS1-001
• Secondary ID: 2017-002140-32
• Status: Completed
• Phase: Phase 1
• Start date: October 6, 2017
• Est. completion date: March 27, 2018

Study information

• Verified date: April 2019
• Source: Cereno Scientific AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 27, 2018
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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)

Exclusion criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, 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. Subjects with active or chronic liver disease or personal or familiar history of drug related severe hepatic dysfunction.

3. Subjects with phorphyria.

4. Subjects with Systemic lupus erytematosus (SLE)

5. Subjects with TPK, APTT, INR levels which are significant outside the reference intervals as judged by the investigator.

6. History of severe bleeding disease or thrombotic disease.

7. Subjects on regular treatment with anticoagulant or antiplatelets drugs

8. Subjects with significant cardiac disease.

9. Subjects with significant pancreatic disease.

10. Subjects with gastrointestinal problems/ diseases e.g. inflammatory bowel disease and irritable bowel syndrome

11. Any clinically significant illness, medical/surgical procedure or trauma within four weeks of the first administration of IMP.

12. Any planned major surgery within the duration of the study.

13. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).

14. After 10 minute supine rest at the time of screening, any vital signs values outside the following ranges:

• Systolic blood pressure > 160 mm Hg

• Diastolic blood pressure > 100 mm Hg

• Heart rate < 40 or > 90 beats per minute

15. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.

16. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to valproate acid or any other ingredient of the investigational medicinal product.

17. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment with less than three months between administration of last dose and first dose of IMP in this study. Subjects consented and screened but not dosed in previous phase I studies are not excluded.

18. Current smokers or users of nicotine products. Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit.

19. Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.

20. Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse.

21. Intake of xanthine and/or taurine containing energy drinks within two days prior to screening.

22. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.

23. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.

Related Conditions & MeSH terms

• Thrombosis

Intervention

Drug:
• CS1-Sodium Valproate
Single and multiple dose evaluation of CS1

Locations

Country	Name	City	State
Sweden	CTC Clinical Trial Consultants AB	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Cereno Scientific AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change in bleeding time	Differences in bleeding time (minutes)	four weeks
Other	Change in plasma PAI-1 levels	ng/mL	four weeks
Other	Change in hs-CRP levels	mg/L	four weeks
Other	Change in platelet numbers	number of platelets per microliter blood	four weeks
Other	Change in fibrinogen levels	g/L	four weeks
Other	Change in PAP	ng/ml	four weeks
Primary	Pharmacokinetic of CS1 in plasma	Plasma concentration of Valproate in plasma	up to four weeks
Secondary	Incidence of Treatment-Emergent Adverse Events	Adverse event recording in free text	up to four weeks