FiH Study to Assess Safety and PK of SAD and MAD of ANT3310 Alone and in Combination With Meropenem in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT05905913
- Lead Sponsor
- Antabio
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
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:
- History of epilepsy (or known seizure disorder), brain lesions or other significant neurological disorders,
- Known history of clinically-significant hypersensitivity or urticaria, or severe allergic reaction to β-lactam antibiotics,
- History of Gilbert syndrome,
- History of any severe antibiotic-associated superinfections,
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Single Intravenous Ascending Dose of ANT3310 ANT3310 - Part A: Single Intravenous Dose of Matching placebo ANT3310-placebo - Part B: Multiple Intravenous Ascending Doses of Matching Placebo ANT3310-placebo - Part C: ANT3310 Placebo + Meropenem Placebo ANT3310-placebo Participants will receive a single dose of ANT3310-placebo or Meropenem-placebo in one of the 2 treatment sequences followed by repeat administrations of ANT3310-placebo + Meropenem-placebo Part C: ANT3310 Placebo + Meropenem Placebo Meropenem-placebo Participants will receive a single dose of ANT3310-placebo or Meropenem-placebo in one of the 2 treatment sequences followed by repeat administrations of ANT3310-placebo + Meropenem-placebo Part B: Multiple Intravenous Ascending Doses of ANT3310 ANT3310 - Part C: ANT3310 + Meropenem ANT3310 Participants will receive a single intravenous dose of ANT3310 or Meropenem in one of the 2 treatment sequences followed by the repeat administrations of ANT3310 + Meropenem. Part C: ANT3310 + Meropenem Meropenem Participants will receive a single intravenous dose of ANT3310 or Meropenem in one of the 2 treatment sequences followed by the repeat administrations of ANT3310 + Meropenem.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 A (SAD): Maximum Plasma Concentration (Cmax) 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): 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 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
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): 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 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 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 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
Trial Locations
- Locations (1)
Biotrial
🇫🇷Rennes, France