Evaluation of the Safety, Tolerability and Pharmacokinetics of Intravenous ETX2514 Administered in Healthy Subjects

A Phase I, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous ETX2514 Administered in Healthy Subjects

This research project is being conducted to look at the safety, tolerability, and pharmacokinetics (PK; how the human body processes a substance) of ETX2514 when given to healthy volunteers intravenously as a single dose, and when given as multiple intravenous doses for up to 8 consecutive days.

As it is anticipated that ETX2514 could be used as a treatment for Acinetobacter baumannii (a type of bacteria) infections, this project will also look at whether ETX2514 will interact with the current treatments for these infections when they are administered at the same time.

This Phase 1, single-center, randomized, double-blind, and placebo-controlled study investigates the safety, tolerability, and PK profile of single and multiple ascending doses of intravenous (IV) ETX2514 when administered intravenously alone and in combination with sulbactam and/or imipenem/cilastatin in healthy adult participants.

The study will be conducted in four Parts: A, B, C, and D. Part A will explore the safety and tolerability of a single ascending dose (SAD) of IV ETX2514 over 8 cohorts. Part B will explore the safety and tolerability of multiple ascending doses (MAD) of IV ETX2514 over 4 cohorts. Part C will explore the safety and tolerability of IV ETX2514 when administered as a single dose in combination with sulbactam (1.0 gram [g]) and/or imipenem/cilastatin (0.5 g) to healthy participants over 2 cohorts. Part D will explore the safety and tolerability of multiple doses of combined IV ETX2514/sulbactam (1.0 g)/imipenem/cilastatin (0.5 g) to healthy participants.

Inclusion Criteria:

• Aged 18 to 55 years (inclusive). In addition, 8 participants greater than or equal to 65 years of age will be enrolled.
• Be in general good health without a clinically significant medical history
• Provide voluntary written informed consent prior to any study procedures and are willing and able to comply with the prescribed treatment protocol and evaluations
• Body mass index (BMI) greater than or equal to 18.0 kilograms (kg)/meters square (m^2) and less than or equal to 32.0 kg/m^2
• Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the Principal Investigator decides that out-of-range values are not clinically significant
• Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen (HBS Ag), hepatitis C virus antibody (HCV Ab), and Human Immunodeficiency Virus (HIV) at screening; and drugs of abuse, alcohol pre dose on Day -1
• Female participants must be of non-childbearing potential, or using a medically acceptable contraceptive regimen and must have a negative pregnancy test at Screening (serum) and on Day -1 (urine) prior to study drug dosing. Male participants must be surgically sterile, or using a medically acceptable contraceptive regimen.

Exclusion Criteria:

• History of any moderate or severe hypersensitivity or allergic reaction to any beta-lactam antimicrobial (e.g., penicillin, cephalosporin, sulbactam, or carbapenem).
• Use of prescription or over the counter medications within 7 days of Investigational Product administration, with the exception of contraceptive medications, paracetamol, oral non-steroidal anti-inflammatory agents, topical over the counter preparations, and routine vitamins (if they do not exceed an intake of 20 to 600 times the recommended daily dose), unless agreed as non-clinically relevant by the Principal Investigator and Sponsor
• Participation in an investigational drug or device study within 30 days before study drug dosing, i.e., there was at least 30 days in between the last dose on a prior study and dose administration on this study
• Current smoker, or difficulty abstaining from smoking for the duration of study confinement
• History of major organ dysfunction
• Infection or any serious underlying medical condition that would impair the participant from receiving study drug
• History of excessive alcohol intake (more than 4 standard drinks daily, on average) or use of recreational drugs within the last 3 months
• Standard donation of blood within 30 days of the study
• Concomitant disease or condition, including laboratory abnormality, which could interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study
• Anticipated need for surgery or hospitalization during the study
• Unwillingness or inability to comply with the study protocol for any other reason