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AzTrials

Acinetobacter Baumannii InfectionPhase 1NCT02971423

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

A Phase 1 study testing ETX2514, Sulbactam and Imipenem/Cilastatin in people with Acinetobacter Baumannii Infection, run by Entasis Therapeutics at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Acinetobacter Baumannii Infection
What is being tested?
ETX2514, Sulbactam and Imipenem/Cilastatin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
124 participants
Where
1 siteAustralia
Study dates
Oct 2016to 1 Jun 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Study site

    Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: 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.

Read the detailed description

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.

Being tested
ETX2514, Placebo, Sulbactam, Imipenem/Cilastatin
Keywords
infection, gram-negative bacterium
Medical subject headings
Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ETX2514Drug

  • PlaceboDrug

    matching placebo infusion

  • SulbactamDrug

  • Imipenem/CilastatinDrug

Study groups in NCT02971423
Study groupRoleWhat they receive
Part A; Cohort 1: 0.25 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a single ascending dose (SAD) of intravenous (IV) ETX2514. Participants in Cohort 1, aged 18 to 55 years, will receive 0.25 grams (g) IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 2: 0.5 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 2, aged 18 to 55 years, will receive 0.5 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 3: 1.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 3, aged 18 to 55 years, will receive 1.0 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 4: 1.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 4, aged 18 to 55 years, will receive 1.0 g IV ETX2514/placebo infused over 2 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 5: 2.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 5, aged 18 to 55 years, will receive 2.0 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 6: 4.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 5, aged 18 to 55 years, will receive 4.0 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 7: 8.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 7, aged 18 to 55 years, will receive 8.0 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part A; Cohort 8: 1.0 g IV ETX2514/placeboExperimentalPart A of the study will explore the safety and tolerability of a SAD of IV ETX2514. Participants in Cohort 8, aged 65 years or older, will receive 1.0 g IV ETX2514/placebo infused over 3 hours.
Receives: Drug: ETX2514; Drug: Placebo
Part B; Cohort 9: 0.25 g IV EXT2514/placeboExperimentalPart B of the study will explore the safety and tolerability of multiple ascending doses (MAD) of IV ETX2514. Participants in Cohort 9, aged 18 to 55 years, will receive 0.25 g IV EXT2514/placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days, and then will receive 1 dose on Day 8.
Receives: Drug: ETX2514; Drug: Placebo
Part B; Cohort 10: 0.5 g IV EXT2514/placeboExperimentalPart B of the study will explore the safety and tolerability of MAD of IV ETX2514. Participants in Cohort 10, aged 18 to 55 years, will receive 0.5 g IV EXT2514/placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days, and then will receive 1 dose on Day 8.
Receives: Drug: ETX2514; Drug: Placebo
Part B; Cohort 11: 1.0 g IV EXT2514/placeboExperimentalPart B of the study will explore the safety and tolerability of MAD of IV ETX2514. Participants in Cohort 11, aged 18 to 55 years, will receive 1.0 g IV EXT2514/placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days, and then will receive 1 dose on Day 8.
Receives: Drug: ETX2514; Drug: Placebo
Part B; Cohort 12: 2.0 g IV EXT2514/placeboExperimentalPart B of the study will explore the safety and tolerability of MAD of IV ETX2514. Participants in Cohort 12, aged 18 to 55 years, will receive 2.0 g IV EXT2514/placebo infused over 3 hours, every 6 hours (4 times a day) for 7 consecutive days, and then will receive 1 dose on Day 8.
Receives: Drug: ETX2514; Drug: Placebo
Part C; Cohort 13: ETX2514/placebo with sulbactamExperimentalPart C of the study will explore the safety and tolerability of IV ETX2514 when administered as a single dose in combination with sulbactam (1.0 g) and/or imipenem/cilastatin (0.5 g) to healthy participants. On Day 1, participants will receive a single dose of 1.0 g IV ETX2514/placebo infused over 3 hours. On Day 3, participants will receive a single dose of 1.0 g IV sulbactam infused over 3 hours. On Day 5, participants will receive a single dose of 1.0 g IV ETX2514/placebo plus 1.0 g sulbactam infused over 3 hours at the same time. The actual Day 1 and Day 5 ETX2514 dose and infusion time will be determined based on PK and safety data from Part A.
Receives: Drug: ETX2514; Drug: Placebo; Drug: Sulbactam
Part C; Cohort 14: ETX2514/placebo with SUL and/or IM/CILExperimentalPart C of the study will explore the safety and tolerability of IV ETX2514 when administered as a single dose in combination with sulbactam (SUL: 1.0 g) and/or imipenem/cilastatin (IM/CIL: 0.5 g) to healthy participants. On Day 1, participants will receive a single dose of 1.0 g IV ETX2514/placebo infused over 3 hours. On Day 3, participants will receive a single dose of 0.5 g IV imipenem/cilastatin infused over 30 minutes. On Day 5, participants will receive a single dose of 1.0 g IV ETX2514/placebo infused over 3 hours plus 0.5 g imipenem/cilastatin infused over 30 minutes initiated at the same time as ETX2514/placebo. On Day 8, participants will receive a single dose of 1.0 g IV ETX2514/placebo plus 1.0 g sulbactam infused over 3 hours at the same time plus 0.5 g imipenem/cilastatin infused over 30 minutes initiated at the same time as ETX2514/placebo. The actual Day 1, Day 5, and Day 8 ETX2514 dose and infusion time will be determined based on PK and safety data from Part A.
Receives: Drug: ETX2514; Drug: Placebo; Drug: Sulbactam; Drug: Imipenem/Cilastatin
Part D; Cohort 15: ETX2514/placebo with SUL and/or IM/CILExperimentalPart D of the study 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. Participants in Cohort 15 will receive 1.0 g IV ETX2514/placebo and 1.0 g IV sulbactam both infused over 3 hours and 0.5 g IV imipenem/cilastatin infused over 30 minutes every 6 hours (4 times a day) for 10 days and will receive 1 dose on Day 11. The actual ETX2514 dose and infusion time will be determined based on PK and safety data from Part C.
Receives: Drug: ETX2514; Drug: Placebo; Drug: Sulbactam; Drug: Imipenem/Cilastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with any non-serious and any serious adverse event

    Measured: up to 14 days after the last infusion of study drug (Study Day 182)

  2. Number of participants with an adverse event of the indicated causality and severity

    Measured: up to 14 days after the last infusion of study drug (Study Day 182)

  3. Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part A

    Measured: Baseline (Day -1); Days 3, 5, 7, and 15 (Follow-up)

  4. Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part B

    Measured: Baseline (Day -1; Study Day [SD] 37); Days 2, 3, 5, 7, and 10 (SDs 39, 40, 42, 44, and 47, respectively); Day 22 (SD 59; Follow-up)

  5. Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part C

    Measured: Cohort 13: Baseline (Day -1; Study Day [SD] 80); Days 3, 4, and 7 (SDs 83, 84, and 87, respectively); Day 19 (SD 99; Follow-up). Cohort 14: Baseline; Days 3, 4, 7, and 10 (SDs 83, 84, 87, and 90, respectively); Day 22 (SD 102; Follow-up)

  6. Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part D

    Measured: Baseline (Day -1; SD 122); Days 2, 3, 5, 7, 10, 11, and 13 (SDs 124, 125, 127, 129, 132, and 133, respectively); Day 25 (SD 147; Follow-up)

  7. Change from Baseline in vital signs at the indicated time points in Part A

    Day 1: prior to infusion, and 1, 3, 6, and 12 hours post start of infusion. Day 2: 24 hours post start of infusion). Day 3: 48 hours post start of infusion

    Measured: Baseline (Day -1); Days 1-3; Day 5; Day 7; Day 15 (Follow-up)

  8. Change from Baseline in vital signs at the indicated time points in Part B

    Days 1-8: 30 minutes prior to infusion and 3, 6, and 12 hours post start of infusion. Day 9: 24 hours post Day 8 start of infusion. Day 10: 48 hours post Day 8 start of infusion

    Measured: Baseline (Day -1; SD 37); Days 1-10 (SDs 38-47, respectively); Day 22 (SD 59; Follow-up)

  9. Change from Baseline in vital signs at the indicated time points in Cohort 13 of Part C

    Days 1, 3, and 5: 30 minutes prior to infusion and 3, 6, and 12 hours post start of infusion. Days 2, 4, and 6: 24 hours post start of infusion. Day 7: 48 hours post Day 5 start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively); Day 19 (SD 99; Follow-up)

  10. Change from Baseline in vital signs at the indicated time points in Cohort 14 of Part C

    Days 1, 3, 5, and 8: 30 minutes prior to infusion and 3, 6, and 12 hours post start of infusion. Days 2, 4, 6, and 9: 24 hours post start of infusion. Days 7 and 10: 48 hours post Day 5 and Day 8, respectively, start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively); Day 22 (SD 102; Follow-up)

  11. Change from Baseline in vital signs at the indicated time points in Part D

    Days 1-11: 30 minutes prior to infusion and 3, 6, and 12 hours post infusion

    Measured: Baseline (SD 122); Days 1-13 (SDs 123-135, respectively); Day 25 (SD 147; Follow-up)

  12. Change from Baseline in electrocardiogram parameters at the indicated time points in Parts A and B

    Part A: Day 1: 150 minutes after start of infusion; Day 3: 48 hours after start of infusion. Part B: Days 1, 3, 5, and 7: 150 minutes after start of infusion; Day 10: 48 hours post Day 8 start of infusion

    Measured: Part A: Baseline (Day -1); Days 1 and 3; Follow-up visit (Day 15). Part B: Baseline (Day -1; SD 37); Days 1, 3, 5, 7, 10, and 22 (SDs 38, 40, 42, 44, 47, and 59, respectively)

  13. Change from Baseline in electrocardiogram parameters at the indicated time points in Cohort 13 in Part C

    Days 1, 3, and 5: 150 minutes post start of infusion; Day 7: 48 hours post Day 5 start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1, 3, 5, and 7 (SDs 81, 83, 85, and 87, respectively); Day 19 (SD 99; Follow-up)

  14. Change from Baseline in electrocardiogram parameters at the indicated time points in Cohort 14 in Part C

    Days 1, 3, 5, and 8: 150 minutes post start of infusion; Day 10: 48 hours post Day 8 start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1, 3, 5, 8, and 10 (SDs 81, 83, 85, 88, and 90, respectively); Day 22 (SD 102; Follow-up)

  15. Change from Baseline in electrocardiogram parameters at the indicated time points in Part D

    Days 1, 3, 5, 7, 9, and 11: 150 minutes post start of infusion. Day 13: 48 hours post Day 11 start of infusion

    Measured: Baseline (SD 122); Days 1, 3, 5, 7, 9, and 11 (SDs 123, 125, 127, 129, 131, and 133, respectively); Day 13 (SD 135); Day 25 (SD 147; Follow-up)

  16. Number of participants with an infusion site reaction

    Measured: up to 14 days after the last infusion of study drug (SD 182)

  17. Mean peak plasma concentration (Cmax) and plasma concentration at time t (Ct) in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  18. Mean Cmax and Ct in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  19. Mean Cmax and Ct in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  20. Mean Cmax and Ct in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  21. Mean Cmax and Ct in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  22. Mean Cmax and Ct in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  23. Mean time to peak plasma concentration (Tmax) in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  24. Mean Tmax in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  25. Mean Tmax in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  26. Mean Tmax in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  27. Mean Tmax in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  28. Mean Tmax in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  29. Mean AUC from time 0 to 24 hours (AUC0-24), AUC from time 0 to the last time point evaluated (AUC0-t), and AUC from time 0 and extrapolated to infinity (AUC0-∞) in blood at the indicated time points in Cohorts 1-3 in Part A

    AUC is defined as area under the concentration time curve. Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  30. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  31. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  32. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  33. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  34. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  35. Mean elimination rate constant (Kel) in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  36. Mean Kel in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  37. Mean Kel in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  38. Mean Kel in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  39. Mean Kel in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  40. Mean Kel in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  41. Mean elimination half-life (t1/2) in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  42. Mean t1/2 in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  43. Mean t1/2 in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  44. Mean t1/2 in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  45. Mean t1/2 in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  46. Mean t1/2 in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  47. Mean clearance in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  48. Mean clearance in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  49. Mean clearance in urine at the indicated time points in Part A

    -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1); Days 1-3

  50. Mean clearance in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  51. Mean clearance in urine at the indicated time points in Part B

    All days: -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 37); Days 1-3 and 7-10 (SDs 38-40 and 44-47, respectively)

  52. Mean clearance in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  53. Mean clearance in urine at the indicated time points in Cohort 13 in Part C

    Day 1 to Day 3 (ETX2514/placebo): from -12 to 0 hours prior to start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 3-5 (sulbactam): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 5-7 (infusion to co-administer ETX2514/placebo and sulbactam): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively)

  54. Mean clearance in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  55. Mean clearance in urine at the indicated time points in Cohort 14 in Part C

    Day 1 to Day 3 (ETX2514/placebo): from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 3 to Day 5 (imipenem/cilastatin): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 5 to Day 7 (infusion to co-administer ETX2514/placebo and imipenem/cilastatin): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 8 to Day 10 (infusion to co-administer ETX2514/placebo, sulbactam, and imipenem/cilastatin): from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively)

  56. Mean clearance in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  57. Mean clearance in urine at the indicated time points in Part D

    Days 1-3: from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 11-13: from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 123); Days 1-3 (SDs 124-126, respectively); Days 10-13 (SDs 133-136, respectively)

  58. Mean volume of distribution (VzVdss) in blood at the indicated time points in Cohorts 1-3 and 5-8 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  59. Mean VzVdss in blood at the indicated time points in Cohort 4 in Part A

    Day 1: 30 minutes prior to infusion; 1, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  60. Mean VzVdss in blood at the indicated time points in Part B

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 8: 30 minutes prior to infusion of the final dose, which is given on Day 8; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 9: 24 and 36 hours post start of infusion. Day 10: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)

  61. Mean VzVdss in blood at the indicated time points in Cohort 13 in Part C

    Day 1: 30 minutes prior to infusion of ETX2514/placebo; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of ETX2514/placebo. Day 2: 24 and 36 hours post start of infusion of ETX2514/placebo. Day 3: immediately prior to start of infusion of sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion of sulbactam. Day 4: 24 and 36 hours post start of infusion of sulbactam. Day 5: immediately prior to infusion to co-administer ETX2514/placebo and sulbactam (48 hours); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 6: 24 and 36 hours post start of infusion to co-administer ETX2514/placebo and sulbactam. Day 7: 48 hours post start of infusion to co-administer ETX2514/placebo and sulbactam

    Measured: Days 1-7 (SDs 81-87, respectively)

  62. Mean VzVdss in blood at the indicated time points in Cohort 14 in Part C

    ETX2514/placebo infusion: Day 1: 30 minutes prior to infusion (PTI); 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion (PSOI). Day 2: 24 and 36 PSOI. Imipenem (IM)/cilastatin (CIL) infusion: Day 3: immediately prior to start of infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 4, 5, 6, 8, and 12 hours PSOI. Day 4: 24 and 36 hours PSOI. Co-administration of ETX2514/placebo and IM/CIL: Day 5: immediately prior to infusion (48 hours); 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours PSOI. Day 6: 24 and 36 hours PSOI. Day 7: 48 hours PSOI. Co-administration of ETX2514/placebo, sulbactam, and IM/CIL: Day 8: 30 minutes prior to infusion; 30 minutes PSOI; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 PSOI. Day 9: 24 and 36 hours PSOI. Day 10: 48 hours PSOI

    Measured: Days 1-10 (SDs 81-90, respectively)

  63. Mean VzVdss in blood at the indicated time points in Part D

    Day 1: 30 minutes prior to infusion; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Days 2 and 4: 30 minutes prior to infusion of the second dose given on Days 2 and 4, respectively. Day 11: 30 minutes prior to infusion of the final dose given on Day 11; 30 minutes post start of infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 12: 24 and 36 hours post start of infusion. Day 13: 48 hours post start of infusion

    Measured: Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)

  64. Mean cumulative excretion of unchanged drug in urine (Ae) at the indicated time points in Part A

    -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1); Days 1-3

  65. Mean Ae at the indicated time points in Part B

    All days: -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 37); Days 1-3 and 7-10 (SDs 38-40 and 44-47, respectively)

  66. Mean Ae at the indicated time points in Cohort 13 in Part C

    Day 1 to Day 3 (ETX2514/placebo): from -12 to 0 hours prior to start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 3-5 (sulbactam): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 5-7 (infusion to co-administer ETX2514/placebo and sulbactam): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively)

  67. Mean Ae at the indicated time points in Cohort 14 in Part C

    Day 1 to Day 3 (ETX2514/placebo): from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 3 to Day 5 (imipenem/cilastatin): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 5 to Day 7 (infusion to co-administer ETX2514/placebo and imipenem/cilastatin): 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Day 8 to Day 10 (infusion to co-administer ETX2514/placebo, sulbactam, and imipenem/cilastatin): from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively)

  68. Mean Ae at the indicated time points in Part D

    Days 1-3: from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion. Days 11-13: from -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Baseline (Day -1; SD 123); Days 1-3 (SDs 124-126, respectively); Days 10-13 (SDs 133-136, respectively)

Secondary outcomes (16)

  1. Number of elderly participants with any non-serious and any serious adverse event

    Measured: up to Day 15

  2. Number of elderly participants with an adverse event of the indicated causality and severity

    Measured: up to Day 15

  3. Number of participants with abnormal, clinically significant hematology and clinical chemistry parameters at the indicted time points in Part A for elderly participants

    Measured: Baseline (Day -1); Days 3, 5, 7, and 15 (Follow-up)

  4. Change from Baseline in vital signs at the indicated time points in Part A for elderly participants

    Day 1: prior to infusion, and 1, 3, 6, and 12 hours post start of infusion. Day 2: 24 hours post start of infusion). Day 3: 48 hours post start of infusion

    Measured: Baseline (Day -1); Days 1-3; Day 5; Day 7; Day 15 (Follow-up)

  5. Change from Baseline in electrocardiogram parameters at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes after start of infusion

    Measured: Baseline (Day -1); Day 1; Day 3; Follow-up visit (Day 15)

  6. Number of elderly participants with an infusion site reaction

    Measured: up to Day 15

  7. Mean Cmax and Ct in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  8. Mean Tmax in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  9. Mean AUC0-24, AUC0-t, and AUC0-∞ in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  10. Mean Kel in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  11. Mean t1/2 in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  12. Mean clearance in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  13. Mean clearance in urine at the indicated time points in Part A for elderly participants

    -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Days 1-3

  14. Mean VzVdss in blood at the indicated time points in Part A for elderly participants

    Day 1: 30 minutes prior to infusion; 1, 2, 3, 3.5, 4, 5, 6, 8, and 12 hours post start of infusion. Day 2: 24 and 36 hours post start of infusion; Day 3: 48 hours post start of infusion

    Measured: Days 1-3

  15. Mean Ae at the indicated time points in Part A for elderly participants

    -12 to 0 hours prior to the start of infusion; 0-6, 6-12, 12-24, and 24-48 hours post start of infusion

    Measured: Days 1-3

  16. Number of elderly participants using concomitant medications

    Measured: up to Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2016 (estimated)
  2. Study startOct 2016
  3. Primary completion1 Jun 2017
  4. Study completion1 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02971423
Sponsor's protocol ID
CS2514-2016-0001
Other IDs
ACTRN12616000995471p
Status last verified
Apr 2017
First submitted
21 Oct 2016
Last updated
5 Jun 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Lickliter JD, Lawrence K, O'Donnell J, Isaacs R. Safety, Pharmacokinetics, and Drug-Drug Interaction Potential of Intravenous Durlobactam, a beta-Lactamase Inhibitor, in Healthy Subjects. Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00071-20. doi: 10.1128/AAC.00071-20. Print 2020 Jun 23.

    PubMed 32284380

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ETX2514, Sulbactam and Imipenem/Cilastatin in people with Acinetobacter Baumannii Infection, run by Entasis Therapeutics at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with any non-serious and any serious adverse event (time frame: up to 14 days after the last infusion of study drug (Study Day 182)). The study lists 68 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02971423, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.

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