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Study Investigation Pharmacokinetics and Pharmacodynamics of CS1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03903302
Recruitment Status : Completed
First Posted : April 4, 2019
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Jan Erik Berglund, Cereno Scientific AB

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.


Condition or disease Intervention/treatment Phase
Thrombosis Drug: CS1-Sodium Valproate Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Safety, pharmacokinetics and pharmacodynamics of CS1
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 6, 2017
Actual Primary Completion Date : February 28, 2018
Actual Study Completion Date : March 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots

Arm Intervention/treatment
Active Comparator: CS 1 I SAD
Single dose pharmacokinetics of CS1 I
Drug: CS1-Sodium Valproate
Single and multiple dose evaluation of CS1

Active Comparator: CS 1 II SAD
Single dose pharmacokinetics of CS1 II
Drug: CS1-Sodium Valproate
Single and multiple dose evaluation of CS1

Active Comparator: CS 1 III SAD
Single dose pharmacokinetics of CS1 III
Drug: CS1-Sodium Valproate
Single and multiple dose evaluation of CS1

Active Comparator: CS 1 II MAD
Multiple dose pharmacokinetics of CS1 II
Drug: CS1-Sodium Valproate
Single and multiple dose evaluation of CS1




Primary Outcome Measures :
  1. Pharmacokinetic of CS1 in plasma [ Time Frame: up to four weeks ]
    Plasma concentration of Valproate in plasma


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: up to four weeks ]
    Adverse event recording in free text


Other Outcome Measures:
  1. change in bleeding time [ Time Frame: four weeks ]
    Differences in bleeding time (minutes)

  2. Change in plasma PAI-1 levels [ Time Frame: four weeks ]
    ng/mL

  3. Change in hs-CRP levels [ Time Frame: four weeks ]
    mg/L

  4. Change in platelet numbers [ Time Frame: four weeks ]
    number of platelets per microliter blood

  5. Change in fibrinogen levels [ Time Frame: four weeks ]
    g/L

  6. Change in PAP [ Time Frame: four weeks ]
    ng/ml



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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:

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.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03903302


Locations
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Sweden
CTC Clinical Trial Consultants AB
Uppsala, Sweden, 75237
Sponsors and Collaborators
Cereno Scientific AB
Investigators
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Study Chair: Niklas Bergh, PhD Cereno Scientific AB
  Study Documents (Full-Text)

Documents provided by Jan Erik Berglund, Cereno Scientific AB:
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Responsible Party: Jan Erik Berglund, Principle Investigator, Cereno Scientific AB
ClinicalTrials.gov Identifier: NCT03903302    
Other Study ID Numbers: CS1-001
2017-002140-32 ( EudraCT Number )
First Posted: April 4, 2019    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jan Erik Berglund, Cereno Scientific AB:
tissue-plasminogen activator (t-PA)
plasminogen-activator inhibitor 1 (PAI-1)
fibrinolysis
thrombosis
Additional relevant MeSH terms:
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Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs