First-in-human, randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of Apta-1.
- Conditions
- blood poisoningSepsis10027665
- Registration Number
- NL-OMON51837
- Lead Sponsor
- Aptahem AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 72
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.
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 <90mL/min/1.73m2.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Parts A+B<br /><br>• Treatment-related (serious) adverse events ([S]AEs).<br /><br>• Concomitant medication.<br /><br>• Vital signs: Systolic blood pressure (mmHg), diastolic blood pressure (mmHg),<br /><br>heart rate (bpm), respiratory rate (bpm), body temperature (°C).<br /><br>• Clinical laboratory tests: hematology, coagulation, blood chemistry and<br /><br>urinalysis as listed in section 6.1.5.<br /><br>• Electrocardiogram (ECG) parameters (Heart Rate (HR) (bpm), PR, QRS, QT,<br /><br>QTcF).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part A<br /><br>Single intravenous dose administration (cohort 1):<br /><br>o AUCinf, AUCinf(%extrap), AUClast, AUC0-1h, CL, Cmax, t1/2, tmax, tlast, Vz.<br /><br>o Dose-normalized PK parameters: AUCinf, AUClast, Cmax.<br /><br><br /><br>Single intravenous dose with split (two equal doses) administration (cohort<br /><br>2-6):<br /><br>o AUC0-1h, AUCinf, AUCinf(%extrap), AUClast, CL, Cmax-dose1, Cmax-dose2,<br /><br>t1/2, tmax, tlast, Vz.<br /><br>o Dose-normalized PK parameters on total dose: Cmax, AUCinf, AUClast<br /><br>o Dose-normalized PK parameters on separate dose: AUC0-1h, Cmax-dose1,<br /><br>Cmax-dose2<br /><br><br /><br>Part B<br /><br>Single intravenous dose with split (two equal doses) administration:<br /><br>o AUC0-1h, AUCinf, AUCinf(%extrap), AUClast, CL, Cmax-dose1, Cmax-dose2, t1/2,<br /><br>tmax, tlast, Vz.<br /><br>o Dose-normalized PK parameters on total dose: AUCinf, AUClast<br /><br>o Dose-normalized PK parameters on separate dose: AUC0-1h, Cmax-dose1,<br /><br>Cmax-dose2</p><br>