blood poisoning Sepsis
Conditions
Interventions
Apta-1 or placebo
Sponsors
Aptahem AB
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Has the ability to communicate well with the Investigator in the Dutch language and is willing and able to comply with all study procedures and give written informed consent prior to any study-mandated procedure. 2. Healthy male and female subjects,18 to 55 years of age, inclusive, at screening. 3. Body mass index (BMI) between 18 and 30 kg/m2 and with a weight between 50 and 100 kg, both inclusive, at screening. 4. 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 (see paragraph 4.5.1.) during the study and be willing and able to continue contraception for respectively at least 180 days (females) and 90 days (males) 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: • Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks after surgical bilateral oophorectomy with or without hysterectomy; • Post-hysterectomy.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition (e.g. history of sepsis, cardiovascular disease, syncope or malignancy) that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3. Hemorrhagic diathesis (e.g. nose bleeds, mucosal bleedings, easy bruising, gastrointestinal bleeding, menorrhagia), as judged by the investigator. 4. Use of any prescription or OTC medications, antibiotics, NSAIDs (such as ibuprofen), aspirin, anti-platelet therapy, anti-coagulation therapy, prophylactic and therapeutic LMWH or un-fractioned heparin within 4 weeks, or 5 half-lives (whichever is longer), prior to first IMP administration. Exception for prescription contraceptives. 5. Any active or ongoing chronic inflammatory or infectious disease including periodontitis except for common viral or fungal skin infections such as plantar warts or athlete*s foot. Additional criteria for part B: 1. Previous participation in a systemic (i.v./inhaled) LPS challenge trial or prior exposure to systemic endotoxin within a year before LPS administration in this study. 2. Significant risk or history of cardiac failure, overfilling and/or developing edema. 3. Estimated glomerular filtration rate (eGFR) of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts A+B • Treatment-related (serious) adverse events ([S]AEs). • Concomitant medication. • Vital signs: Systolic blood pressure (mmHg), diastolic blood pressure (mmHg), heart rate (bpm), respiratory rate (bpm), body temperature (°C). • Clinical laboratory tests: hematology, coagulation, blood chemistry and urinalysis as listed in section 6.1.5. • Electrocardiogram (ECG) parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcF). | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A Single intravenous dose administration (cohort 1): o AUCinf, AUCinf(%extrap), AUClast, AUC0-1h, CL, Cmax, t1/2, tmax, tlast, Vz. o Dose-normalized PK parameters: AUCinf, AUClast, Cmax. Single intravenous dose with split (two equal doses) administration (cohort 2-6): o AUC0-1h, AUCinf, AUCinf(%extrap), AUClast, CL, Cmax-dose1, Cmax-dose2, t1/2, tmax, tlast, Vz. o Dose-normalized PK parameters on total dose: Cmax, AUCinf, AUClast o Dose-normalized PK parameters on separate dose: AUC0-1h, Cmax-dose1, Cmax-dose2 Part B Single intravenous dose with split (two equal doses) administration: o AUC0-1h, AUCinf, AUCinf(%extrap), AUClast, CL, Cmax-dose1, Cmax-dose2, t1/2, tmax, tlast, Vz. o Dose-normalized PK parameters on total dose: AUCinf, AUClast o Dose-normalized PK parameters on separate dose: AUC0-1h, Cmax-dose1, Cmax-dose2 | — |
Countries
Netherlands
Outcome results
None listed