An interventional study to evaluate the Safety and Pharmacokinetics (PK, the measure of how the human body processes a substance) of ETX2514 when administered intravenously (IV, directly into the bloodstream through a vein in the arm) to healthy participants.

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12616000995471

Enrollment

124

Registered

2016-07-28

Start date

2016-10-03

Completion date

2017-05-04

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This research project is being conducted to look at the safety, tolerability and pharmacokinetics (PK, how the human body processes a substance) of a 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.

Interventions

Part A- Single Ascending Dose (SAD) Cohort 1- 0.25g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 2- 0.5g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 3- 1g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 4- 1g IV ETX2514/ placebo infused over 2 hours to participants aged 18-55 Cohort 5- 2g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 6- 4g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 7- 8g IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 8- 1g IV ETX2514/ placebo infused over 3 hours in elderly subjects (aged 65 years or older) Participants will be confined to the study unit from Day-1 until 48 hours post dose (Day 3), and will be confined to bed during the infusion. Part B- Multiple Ascending Dose (MAD) Cohort 9- 0.25g IV EXT2514/ placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days and 1 dose on Day 8 to participants aged 18-55 Cohort 10- 0.5g IV EXT2514/ placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days and 1 dose on Day 8 to participants aged 18-55 Cohort 11- 1g IV EXT2514/ placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days and 1 dose on Day 8 to participants aged 18-55 Cohort 12- 2g IV EXT2514/ placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days and 1 dose on Day 8 to participants aged 18-55 Participants will be confined to the study unit from Day-1 until 48 hours post Day 8 dose (Day 10), and will be confined to bed during each infusion. Part C- single dose EXT2514 in combination with sulbactam and/or primaxin. Cohort 13, Day 1- single dose of 1g* IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 13, Day 3- single dose of 1g IV sulbactam infused over 3 hours to participants aged 18-55 Cohort 13, Day 5- single dose of 1g* IV ETX2514/ placebo plus 1g sulbactam infused over 3 hours at the same time to participants aged 18-55 Cohort 14, Day 1- single dose of 1g* IV ETX2514/ placebo infused over 3 hours to participants aged 18-55 Cohort 14, Day 3- single dose of 0.5g IV primaxin infused over 30 minutes to participants aged 18-55 Cohort 14, Day 5- single dose of 1g* IV ETX2514/ placebo infused over 3 hours plus 0.5g IV primaxin infused over 30 minutes at the same time to participants aged 18-55 Cohort 14, Day 8- single dose of 1g* IV ETX2514/ placebo plus 1g sulbactam infused over 3 hours plus 0.5g IV primaxin infused over 30 minutes at the same time to participants aged 18-55 *The actual ETX2514 dose and infusion time studied in part C will be determined based on PK and safety data from Part A. Participants will be confined to the study unit from Day-1 until 48 hours post Day 5 dose (Day 7), and will be confined to bed during each infusion. Part D- multiple dose EXT2514 in combination with sulbactam and/or primaxin. Cohort 15- 1g* IV ETX2514/ placebo plus 1g sulbactam infused over 3 hours plus 0.5g IV primaxin infused over 30 minutes at the same time, every 6 hours (4 times a day) for 10 consecutive days and 1 dose on Day 11 to participants aged 18-55 *The actual ETX2514 dose and infusion time studied in Part D will be determined based on PK and safety data from Part A. Participants will be confined to the study unit from Day-1 until 48 hours post Day 8 dose (Day 10), and will be confined to bed during each infusion. A triple lumen catheter will be used allowing the concurrent infusion of up to three drugs through a single line.

Study design

Allocation

Randomised controlled trial

Intervention model

Other

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

1. Aged 18 to 55 years (inclusive). In addition, 8 subjects greater than or equal to 65 years of age will be enrolled. 2. Be in general good health without clinically significant medical history. 3. Provide voluntary written informed consent prior to any study procedures and are willing and able to comply with the prescribed treatment protocol and evaluations. 4. Body mass index (BMI) greater than or equal to 18.0 kg/m^2 and less than or equal to 32.0 kg/m^2. 5. 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. 6. 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. 7. Female subjects 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 subjects must be surgically sterile, or using a medically acceptable contraceptive regimen.

Exclusion criteria

1. History of any moderate or severe hypersensitivity or allergic reaction to any beta-lactam antimicrobial (e.g., penicillin, cephalosporin, sulbactam or carbapenem). 2. 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. 3. 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. 4. Current smoker, or difficulty abstaining from smoking for the duration of study confinement. 5. History of major organ dysfunction. 6. Infection or any serious underlying medical condition that would impair the subject from receiving study drug. 7. History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last 3 months. 8. Standard donation of blood within 30 days of the study. 9. 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 subject in this study. 10. Anticipated need for surgery or hospitalization during the study 11. Unwillingness or inability to comply with the study protocol for any other reason.

Outcome results