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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05905913
• Other study ID #: ANT3310-1001
• Status: Completed
• Phase: Phase 1
• Start date: April 12, 2023
• Est. completion date: January 5, 2024

Study information

• Verified date: March 2024
• Source: Antabio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: January 5, 2024
• Est. primary completion date: January 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 ß-lactam antibiotics,

3. History of Gilbert syndrome,

4. History of any severe antibiotic-associated superinfections,

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• ANT3310
ANT3310 will be infused over 3 hours
• ANT3310-placebo
ANT3310-placebo will be infused over 3 hours
• ANT3310
ANT3310 will be infused over 3 hours every 8 hours
• ANT3310-placebo
ANT3310-placebo will be infused over 3 hours every 8 hours
• ANT3310-placebo
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.
• ANT3310
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.
• Meropenem
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.
• Meropenem-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.

Locations

Country	Name	City	State
France	Biotrial	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Antabio

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone	Pharmacokinetic parameter of ANT3310 in plasma	24 hours
Secondary	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
Secondary	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
Secondary	Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone	Pharmacokinetic parameter of ANT3310 in plasma	24 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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