FiH Study to Assess Safety and PK of SAD and MAD of ANT3310 Alone and in Combination With Meropenem in Healthy Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ANT3310
* Drug: ANT3310-placebo
* Drug: ANT3310
* Drug: ANT3310-placebo
* Drug: ANT3310-placebo
* Drug: ANT3310
* Drug: Meropenem
* Drug: Meropenem-placebo


Participation Criteria
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Eligibility Criteria
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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: 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,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Intravenous Ascending Dose of ANT3310<br> | Drug: ANT3310<br>* ANT3310 will be infused over 3 hours<br>|
| Placebo Comparator: Part A: Single Intravenous Dose of Matching placebo<br> | Drug: ANT3310-placebo<br>* ANT3310-placebo will be infused over 3 hours<br>|
| Experimental: Part B: Multiple Intravenous Ascending Doses of ANT3310<br> | Drug: ANT3310<br>* ANT3310 will be infused over 3 hours every 8 hours<br>|
| Placebo Comparator: Part B: Multiple Intravenous Ascending Doses of Matching Placebo<br> | Drug: ANT3310-placebo<br>* ANT3310-placebo will be infused over 3 hours every 8 hours<br>|
| Experimental: Part C: ANT3310 + Meropenem<br>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. | Drug: ANT3310<br>* ANT3310 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.<br>Drug: Meropenem<br>* 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.<br>|
| Placebo Comparator: Part C: ANT3310 Placebo + Meropenem Placebo<br>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 | Drug: ANT3310-placebo<br>* ANT3310-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.<br>Drug: Meropenem-placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | up to 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | 24 hours | 
| Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | 24 hours | 
| Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | 24 hours | 
| Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | 24 hours | 
| Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | Day 1, Day 7 | 
| Part B (MAD): Area under the concentration time curve (AUC) of multiple i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | Day 1, Day 7 | 
| Part B (MAD): Time to maximum plasma concentration (Tmax) of multiple i.v. ascending doses of ANT3310 alone | Pharmacokinetic parameter of ANT3310 in plasma | Day 1, Day 7 | 
| Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of a single i.v. dose of ANT3310 and meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 1, Day 3, Day 5 | 
| Part C (DDI and combination): Area under the concentration time curve (AUC) of a single i.v. dose of ANT3310 and meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 1, Day 3, Day 5 | 
| Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of a single i.v. dose of ANT3310 and meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 1, Day 3, Day 5 | 
| Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of multiple i.v. dose of ANT3310 co-administered with meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 11 | 
| Part C (DDI and combination): Area under the concentration time curve (AUC) of multiple i.v. dose of ANT3310 co-administered with meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 11 | 
| Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of multiple i.v. dose of ANT3310 co-administered with meropenem | Pharmacokinetic parameter of ANT3310 and meropenem in plasma | Day 11 |