A study to investigate the effects of sevuparin on lipopolysaccharide responses and the interaction between enoxaparin and sevuparin in healthy volunteers
- Conditions
- ovel treatment for systemic inflammation disorders such as endotoxemia and sepsis.Circulatory System
- Registration Number
- ISRCTN62166961
- Lead Sponsor
- Modus Therapeutics (Sweden)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 83
1. Healthy male and female volunteers aged 18 to 55 years, inclusive. Health status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis;
2. BMI in the range of 18 to 30 kg/m², and a minimum body weight of 50 kg and a maximal body weight of 112 kg;
3. No history of trauma with likely damage to the spleen or surgery to spleen;
4. Free from any clinically significant febrile illness 30 days preceding study Day 1.
1. History of sepsis, cardiovascular disease, syncope or malignancy;
2. Haemorrhagic diathesis (easy bruising, epistaxis, gastro-intestinal bleeding);
3. First degree family history of premature cardiovascular disease event (if diagnosed before 50 years of age);
4. Previous participation in a systemic (i.v./inhaled) LPS challenge trial or prior exposure to systemic endotoxin within a year before the first study day (applicable to Part 1 and 2 only) or previous exposure to sevuparin in study Part 1 or 2 (applicable to Part 3 only);
5. Subjects who have received any of the following excluded medications within prescribed 14 days of the first dose administration: aspirin, anti-platelet therapy, anticoagulant therapy and prophylactic and therapeutic LMWH or unfractioned heparin;
6. Subjects who have received prophylactic/therapeutic LMWH or unfractioned heparin within the last year;
7. Subjects who have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e. atopic dermatitis); including tattoos (applicable to Part 1 and 2 only).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part 1 (ID LPS) basal cutaneous perfusion measured using a laser speckle contrast imager on day -1, day 1 and day 2.<br>Part 2 (IV LPS) safety and tolerability measured using the following:<br>2.1. Vital signs on day 1 to 3 and day 8 (up to day 10)<br>2.2. Treatment-Emergent Adverse Events on day 1 to day 8 (up to day 10) <br>2.3. Electrocardiography on day 1 to 2 and day 8 (up to day 10) <br>2.4. Haematology and chemistry blood panels, including heparin-induced thrombocytopenia antibodies, at day 1 to 3 and day 8 (up to day 10) <br>2.5. Subjective assessment of feeling sick on a numeric rating scale on day 1 and 2. <br>Part 3 is to assess magnitude of any pharmacodynamic interactions in terms of coagulation parameters measured using APTT, PT, INR, fibrinogen, anti-factor Xa activity, anti-factor IIa activity and D-dimer concentration on day 1 and 2.<br>
- Secondary Outcome Measures
Name Time Method 1. Changes in immune cells and inflammatory cytokines measured using flow cytometry and MesoScale Discovery from baseline up to 48 h post-dose (Part 1 and Part 2). <br>2. Safety and tolerability endpoints measured using vital signs, Treatment-Emergent Adverse Events, electrocardiography and haematology and chemistry blood panels, including heparin-induced thrombocytopenia antibodies (if indicated), at baseline and up to 8-10 days post-dose (Part 1 and Part 3).<br>3. Pharmacokinetic endpoints measured using a heparin red assay method at baseline and up to 24 h post-dose (Part 2). <br>