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
Overview
- Phase
- Phase 1
- Intervention
- ANT3310
- Conditions
- Healthy Volunteers
- Sponsor
- Antabio
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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,
Arms & Interventions
Part A: Single Intravenous Ascending Dose of ANT3310
Intervention: ANT3310
Part A: Single Intravenous Dose of Matching placebo
Intervention: ANT3310-placebo
Part B: Multiple Intravenous Ascending Doses of ANT3310
Intervention: ANT3310
Part B: Multiple Intravenous Ascending Doses of Matching Placebo
Intervention: ANT3310-placebo
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.
Intervention: ANT3310
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.
Intervention: Meropenem
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
Intervention: ANT3310-placebo
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
Intervention: Meropenem-placebo
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part B (MAD): Time to maximum plasma concentration (Tmax) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of multiple i.v. dose of ANT3310 co-administered with meropenem(Day 11)
- Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of multiple i.v. dose of ANT3310 co-administered with meropenem(Day 11)
- 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)
- 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)
- 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)
- Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- Part B (MAD): Area under the concentration time curve (AUC) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- 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)