Study Investigation Pharmacokinetics and Pharmacodynamics of CS1

NCT03903302 | Completed Phase 1

• 2 other identifiers: CS1-0012017-002140-32
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombosis

Keywords

tissue-plasminogen activator (t-PA); plasminogen-activator inhibitor 1 (PAI-1); fibrinolysis; thrombosis

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic of CS1 in plasma

  Plasma concentration of Valproate in plasma

  up to four weeks

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  up to four weeks

Other Outcomes (6)

• change in bleeding time

  four weeks

• Change in plasma PAI-1 levels

  four weeks

• Change in hs-CRP levels

  four weeks

Study Arms (4)

CS 1 I SAD

ACTIVE COMPARATOR

Single dose pharmacokinetics of CS1 I

Drug: CS1-Sodium Valproate

CS 1 II SAD

ACTIVE COMPARATOR

Single dose pharmacokinetics of CS1 II

Drug: CS1-Sodium Valproate

CS 1 III SAD

ACTIVE COMPARATOR

Single dose pharmacokinetics of CS1 III

Drug: CS1-Sodium Valproate

CS 1 II MAD

ACTIVE COMPARATOR

Multiple dose pharmacokinetics of CS1 II

Drug: CS1-Sodium Valproate

Interventions

CS1-Sodium Valproate DRUG

Single and multiple dose evaluation of CS1

CS 1 I SAD; CS 1 II MAD; CS 1 II SAD; CS 1 III SAD

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent for participation in the study
• Male and female subjects age ≥ 40 years, ≤ 75 years inclusive.
• BMI 27- 35 kg/m2
• PAI-1 levels minimum 15 kIE/L (applies only to the MAD study)
• 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.
• 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 .
• 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) -

You may not qualify if:

• Diagnosis and main eligibility criteria
• Willing and able to give written informed consent for participation in the study
• Male and female subjects age ≥ 40 years, ≤ 75 years inclusive.
• BMI 27- 35 kg/m2
• PAI-1 levels minimum 15 kIE/L (applies only to the MAD study)
• 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.
• 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 .
• 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)
• 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.
• Subjects with active or chronic liver disease or personal or familiar history of drug related severe hepatic dysfunction.
• Subjects with phorphyria.
• Subjects with Systemic lupus erytematosus (SLE)
• Subjects with TPK, APTT, INR levels which are significant outside the reference intervals as judged by the investigator.
• History of severe bleeding disease or thrombotic disease.
• Subjects on regular treatment with anticoagulant or antiplatelets drugs

Sponsors & Collaborators

• Cereno Scientific AB: lead

Study Sites (1)

CTC Clinical Trial Consultants AB

Uppsala, 75237, Sweden

Location

MeSH Terms

Conditions

Thrombosis

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Niklas Bergh, PhD

  Cereno Scientific AB

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Safety, pharmacokinetics and pharmacodynamics of CS1

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 4, 2019
• Study Start: October 6, 2017
• Primary Completion: February 28, 2018
• Study Completion: March 27, 2018
• Last Updated: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)