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

March 13, 2024 updated by: Antabio

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rennes, France, 35042
        • Biotrial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

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)
Time Frame: 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
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
Time Frame: 24 hours
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
Time Frame: 24 hours
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
Time Frame: 24 hours
Pharmacokinetic parameter of ANT3310 in plasma
24 hours
Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone
Time Frame: 24 hours
Pharmacokinetic parameter of ANT3310 in plasma
24 hours
Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone
Time Frame: Day 1, Day 7
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
Time Frame: Day 1, Day 7
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
Time Frame: Day 1, Day 7
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
Time Frame: Day 1, Day 3, Day 5
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
Time Frame: Day 1, Day 3, Day 5
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
Time Frame: Day 1, Day 3, Day 5
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
Time Frame: Day 11
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
Time Frame: Day 11
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
Time Frame: Day 11
Pharmacokinetic parameter of ANT3310 and meropenem in plasma
Day 11

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Antabio

Investigators

  • Principal Investigator: Sophie Hays, MD, Biotrial

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 12, 2023

Primary Completion (Actual)

January 5, 2024

Study Completion (Actual)

January 5, 2024

Study Registration Dates

First Submitted

May 19, 2023

First Submitted That Met QC Criteria

June 13, 2023

First Posted (Actual)

June 15, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANT3310-1001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe