A randomized, placebo-controlled study to evaluate the effects of intravenous sevuparin on dermal and systemic LPS responses and the interaction between subcutaneous enoxaparin and sevuparin on coagulation responses in healthy volunteers.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 64

Inclusion Criteria

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, a minimum body weight of 50 kg and a
maximum body weight of 112 kg;
3. Be able to abstain from smoking from 24 hours prior to dosing until study
discharge visit;
4. No history of alcohol or drug abuse;
5. No history of trauma with likely damage to the spleen or surgery to spleen;
6. Free from any clinically significant febrile illness 30 days preceding study
Day 1;
7. Non-atopic constitution, including non-asthmatic;
8. Fitzpatrick skin type I-III (applicable to Part 1 and 2 only);
9. No use of any prescription drugs, including aspirin or other non-steroid
anti-inflammatory drugs;
10. Able to give written informed consent and willing to comply with all
study-related procedures;
11. Female subjects of childbearing potential and male subjects who have sexual
intercourse with a woman of childbearing potential must be willing to practice
effective contraception during the study and be willing and able to continue
contraception for at least 90 days after their last dose of study treatment.
Women of childbearing potential are defined as all women physiologically
capable of becoming pregnant, unless they meet one of the following conditions:
• Postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks
after surgical bilateral oophorectomy with or without hysterectomy;
• Posthysterectomy.
For the purposes of the study, effective contraception is defined as follows:
• Females: Using 1 or more of the following acceptable methods of
contraception: surgical sterilization (e.g., bilateral tubal ligation),
intrauterine contraception/device, hormonal contraception, or any 2 barrier
methods (a combination of male or female condom with diaphragm, sponge or
cervical cap).
• Males: Effective male contraception includes a vasectomy with negative semen
analysis at follow up, or the use of condoms.
Abstinence can be considered an acceptable method of contraception at the
discretion of the investigator. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post ovulation methods) and withdrawal are not considered
acceptable methods of contraception.

Exclusion Criteria

1. History of sepsis or history of clinically significant 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
un-fractioned heparin
6. Subjects who have received prophylactic/therapeutic LMWH or un-fractioned
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).
8. Subject is female and is pregnant (based upon serum pregnancy test at
screening and urine pregnancy test pre-dose to the first sevuparin/placebo
administration), breast-feeding, or planning to become pregnant during the
study or within 90 days after last dose of study treatment.