Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of single and multiple intravenous ascending doses of ANT3310, a novel, specific, competitive inhibitor of serine β-lactamases, alone and in combination with meropenem in healthy subjects.
Interventions
DRUGANT3310
ANT3310 will be infused over 3 hours
DRUGANT3310-placebo
ANT3310-placebo will be infused over 3 hours
DRUGMeropenem
Meropenem will be infused over 3 hours as a single dose as part of the drug-drug interaction study, then every 8 hours as part of the repeat doses study.
DRUGMeropenem-placebo
Meropenem-placebo will be infused over 3 hours as a single dose as part of the drug-drug interaction study, then every 8 hours as part of the repeat doses study.
Sponsors
Antabio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: * Participant capable of giving signed informed consent * Contraceptive use by women or men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Participants are overtly healthy as determined by a medical evaluation including medical history without clinically relevant pathologies, physical examination, vital signs, ECG assessment, and clinical laboratory result * eGFR ≥ 90 mL/min and \< 160 mL/min for males or \< 150 mL/min for females * Body weight within 50.0 and 100.0 kg and BMI within 18.0 and 30.0 kg/m2 Main
Exclusion criteria
* History of any clinically-relevant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrine, haematologic, neuromuscular or allergic disease(s), metabolic disorder, cancer, cirrhosis, significant acute infection, local infection within 2 weeks of dose administration, * ECG: any history of clinically-significant ECG abnormalities, an uninterpretable ECG, or any of ECG abnormalities, unless considered not significant by the Investigator * Abnormalities in clinical chemical, haematological, or coagulation variables considered medically relevant by the Investigator, * Positive urine drug screen, positive breathalyzer for alcohol * Positive results in any of the following virology tests: HIV-1 and -2 antibodies, HBsAg, and anti-hepatitis C virus antibody * Positive SARS-CoV-2 antigen test * Women who are pregnant or nursing, * Donation or loss of over 500 mL of blood within sixty days prior to the first study drug administration, Part C with co-administration of meropenem: 1. History of epilepsy (or known seizure disorder), brain lesions or other significant neurological disorders, 2. Known history of clinically-significant hypersensitivity or urticaria, or severe allergic reaction to β-lactam antibiotics, 3. History of Gilbert syndrome, 4. History of any severe antibiotic-associated superinfections,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and severity of Treatment Emergent Adverse Events (TEAE) to evaluate the safety and tolerability profile of single and multiple intravenous ascending doses of ANT3310 alone (Part A and B) and in combination with meropenem (Part C) | up to 11 days | Percentage of subjects who experience at least one TEAE, including abnormalities in vital signs, physical examinations, laboratory safety tests and ECG, by seriousness, intensity, and relatedness |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone | 24 hours | Pharmacokinetic parameter of ANT3310 in plasma |
| Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone | 24 hours | Pharmacokinetic parameter of ANT3310 in plasma |
| Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone | 24 hours | Pharmacokinetic parameter of ANT3310 in plasma |
| Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone | Day 1, Day 7 | Pharmacokinetic parameter of ANT3310 in plasma |
| Part B (MAD): Area under the concentration time curve (AUC) of multiple i.v. ascending doses of ANT3310 alone | Day 1, Day 7 | Pharmacokinetic parameter of ANT3310 in plasma |
| Part B (MAD): Time to maximum plasma concentration (Tmax) of multiple i.v. ascending doses of ANT3310 alone | Day 1, Day 7 | Pharmacokinetic parameter of ANT3310 in plasma |
| Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone | 24 hours | Pharmacokinetic parameter of ANT3310 in plasma |
| Part C (DDI and combination): Area under the concentration time curve (AUC) of a single i.v. dose of ANT3310 and meropenem | Day 1, Day 3, Day 5 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
| Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of a single i.v. dose of ANT3310 and meropenem | Day 1, Day 3, Day 5 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
| Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of multiple i.v. dose of ANT3310 co-administered with meropenem | Day 11 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
| Part C (DDI and combination): Area under the concentration time curve (AUC) of multiple i.v. dose of ANT3310 co-administered with meropenem | Day 11 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
| Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of multiple i.v. dose of ANT3310 co-administered with meropenem | Day 11 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
| Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of a single i.v. dose of ANT3310 and meropenem | Day 1, Day 3, Day 5 | Pharmacokinetic parameter of ANT3310 and meropenem in plasma |
Countries
France
Outcome results
None listed