Clinical trial NCT05905913: FiH Study to Assess Safety and PK of SAD and MAD of ANT3310 Alone and in Combination With Meropenem in Healthy Subjects
Official title: Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single- and Multiple-Ascending Doses of Intravenous ANT3310 Alone and in Combination With Meropenem in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Antabio
Sponsor class: INDUSTRY
First posted: 2023-06-15
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.


Eligibility 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,

Primary outcomes:
measure: 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)
timeFrame: up to 11 days
Secondary outcomes:
measure: Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone
timeFrame: 24 hours
measure: Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone
timeFrame: 24 hours
measure: Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone
timeFrame: 24 hours
measure: Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone
timeFrame: 24 hours
measure: Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone
timeFrame: Day 1, Day 7
measure: Part B (MAD): Area under the concentration time curve (AUC) of multiple i.v. ascending doses of ANT3310 alone
timeFrame: Day 1, Day 7
measure: Part B (MAD): Time to maximum plasma concentration (Tmax) of multiple i.v. ascending doses of ANT3310 alone
timeFrame: Day 1, Day 7
measure: Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of a single i.v. dose of ANT3310 and meropenem
timeFrame: Day 1, Day 3, Day 5
measure: Part C (DDI and combination): Area under the concentration time curve (AUC) of a single i.v. dose of ANT3310 and meropenem
timeFrame: Day 1, Day 3, Day 5
measure: Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of a single i.v. dose of ANT3310 and meropenem
timeFrame: Day 1, Day 3, Day 5
measure: Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of multiple i.v. dose of ANT3310 co-administered with meropenem
timeFrame: Day 11
measure: Part C (DDI and combination): Area under the concentration time curve (AUC) of multiple i.v. dose of ANT3310 co-administered with meropenem
timeFrame: Day 11
measure: Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of multiple i.v. dose of ANT3310 co-administered with meropenem
timeFrame: Day 11
Other outcomes:
Locations:
city: Rennes
country: France
facility: Biotrial
Study officials:
affiliation: Biotrial
name: Sophie Hays, MD
role: PRINCIPAL_INVESTIGATOR
References: