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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02971423




Registration number
NCT02971423
Ethics application status
Date submitted
21/10/2016
Date registered
23/11/2016
Date last updated
5/06/2017

Titles & IDs
Public title
Evaluation of the Safety, Tolerability and Pharmacokinetics of Intravenous ETX2514 Administered in Healthy Subjects
Scientific title
A Phase I, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous ETX2514 Administered in Healthy Subjects
Secondary ID [1] 0 0
ACTRN12616000995471p
Secondary ID [2] 0 0
CS2514-2016-0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acinetobacter Baumannii Infection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ETX2514
Treatment: Drugs - Placebo
Treatment: Drugs - Sulbactam
Treatment: Drugs - Imipenem/Cilastatin

Experimental: Part A; Cohort 1: 0.25 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 2: 0.5 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 3: 1.0 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 4: 1.0 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 5: 2.0 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 6: 4.0 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 7: 8.0 g IV ETX2514/placebo - Part 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.

Experimental: Part A; Cohort 8: 1.0 g IV ETX2514/placebo - Part 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.

Experimental: Part B; Cohort 9: 0.25 g IV EXT2514/placebo - Part 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.

Experimental: Part B; Cohort 10: 0.5 g IV EXT2514/placebo - Part 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.

Experimental: Part B; Cohort 11: 1.0 g IV EXT2514/placebo - Part 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.

Experimental: Part B; Cohort 12: 2.0 g IV EXT2514/placebo - Part 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.

Experimental: Part C; Cohort 13: ETX2514/placebo with sulbactam - Part 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.

Experimental: Part C; Cohort 14: ETX2514/placebo with SUL and/or IM/CIL - Part 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.

Experimental: Part D; Cohort 15: ETX2514/placebo with SUL and/or IM/CIL - Part 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.


Treatment: Drugs: ETX2514


Treatment: Drugs: Placebo
matching placebo infusion

Treatment: Drugs: Sulbactam


Treatment: Drugs: Imipenem/Cilastatin


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with any non-serious and any serious adverse event
Timepoint [1] 0 0
up to 14 days after the last infusion of study drug (Study Day 182)
Primary outcome [2] 0 0
Number of participants with an adverse event of the indicated causality and severity
Timepoint [2] 0 0
up to 14 days after the last infusion of study drug (Study Day 182)
Primary outcome [3] 0 0
Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part A
Timepoint [3] 0 0
Baseline (Day -1); Days 3, 5, 7, and 15 (Follow-up)
Primary outcome [4] 0 0
Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part B
Timepoint [4] 0 0
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)
Primary outcome [5] 0 0
Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part C
Timepoint [5] 0 0
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)
Primary outcome [6] 0 0
Number of participants with abnormal, clinically significant hematology and clinical chemistry laboratory values at the indicated time points in Part D
Timepoint [6] 0 0
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)
Primary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline (Day -1); Days 1-3; Day 5; Day 7; Day 15 (Follow-up)
Primary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline (Day -1; SD 37); Days 1-10 (SDs 38-47, respectively); Day 22 (SD 59; Follow-up)
Primary outcome [9] 0 0
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
Timepoint [9] 0 0
Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively); Day 19 (SD 99; Follow-up)
Primary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively); Day 22 (SD 102; Follow-up)
Primary outcome [11] 0 0
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
Timepoint [11] 0 0
Baseline (SD 122); Days 1-13 (SDs 123-135, respectively); Day 25 (SD 147; Follow-up)
Primary outcome [12] 0 0
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
Timepoint [12] 0 0
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)
Primary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline (Day -1; SD 80); Days 1, 3, 5, and 7 (SDs 81, 83, 85, and 87, respectively); Day 19 (SD 99; Follow-up)
Primary outcome [14] 0 0
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
Timepoint [14] 0 0
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)
Primary outcome [15] 0 0
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
Timepoint [15] 0 0
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)
Primary outcome [16] 0 0
Number of participants with an infusion site reaction
Timepoint [16] 0 0
up to 14 days after the last infusion of study drug (SD 182)
Primary outcome [17] 0 0
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
Timepoint [17] 0 0
Days 1-3
Primary outcome [18] 0 0
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
Timepoint [18] 0 0
Days 1-3
Primary outcome [19] 0 0
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
Timepoint [19] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [20] 0 0
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
Timepoint [20] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [21] 0 0
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
Timepoint [21] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [22] 0 0
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
Timepoint [22] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [23] 0 0
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
Timepoint [23] 0 0
Days 1-3
Primary outcome [24] 0 0
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
Timepoint [24] 0 0
Days 1-3
Primary outcome [25] 0 0
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
Timepoint [25] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [26] 0 0
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
Timepoint [26] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [27] 0 0
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
Timepoint [27] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [28] 0 0
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
Timepoint [28] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [29] 0 0
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 (AUC0-8) 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
Timepoint [29] 0 0
Days 1-3
Primary outcome [30] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [30] 0 0
Days 1-3
Primary outcome [31] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [31] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [32] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [32] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [33] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [33] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [34] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [34] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [35] 0 0
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
Timepoint [35] 0 0
Days 1-3
Primary outcome [36] 0 0
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
Timepoint [36] 0 0
Days 1-3
Primary outcome [37] 0 0
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
Timepoint [37] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [38] 0 0
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
Timepoint [38] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [39] 0 0
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
Timepoint [39] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [40] 0 0
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
Timepoint [40] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [41] 0 0
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
Timepoint [41] 0 0
Days 1-3
Primary outcome [42] 0 0
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
Timepoint [42] 0 0
Days 1-3
Primary outcome [43] 0 0
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
Timepoint [43] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [44] 0 0
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
Timepoint [44] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [45] 0 0
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
Timepoint [45] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [46] 0 0
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
Timepoint [46] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [47] 0 0
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
Timepoint [47] 0 0
Days 1-3
Primary outcome [48] 0 0
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
Timepoint [48] 0 0
Days 1-3
Primary outcome [49] 0 0
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
Timepoint [49] 0 0
Baseline (Day -1); Days 1-3
Primary outcome [50] 0 0
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
Timepoint [50] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [51] 0 0
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
Timepoint [51] 0 0
Baseline (Day -1; SD 37); Days 1-3 and 7-10 (SDs 38-40 and 44-47, respectively)
Primary outcome [52] 0 0
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
Timepoint [52] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [53] 0 0
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
Timepoint [53] 0 0
Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively)
Primary outcome [54] 0 0
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
Timepoint [54] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [55] 0 0
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
Timepoint [55] 0 0
Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively)
Primary outcome [56] 0 0
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
Timepoint [56] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [57] 0 0
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
Timepoint [57] 0 0
Baseline (Day -1; SD 123); Days 1-3 (SDs 124-126, respectively); Days 10-13 (SDs 133-136, respectively)
Primary outcome [58] 0 0
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
Timepoint [58] 0 0
Days 1-3
Primary outcome [59] 0 0
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
Timepoint [59] 0 0
Days 1-3
Primary outcome [60] 0 0
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
Timepoint [60] 0 0
Days 1, 2, 4, 8, 9, and 10 (SDs 38, 39, 41, 45, 46, and 47, respectively)
Primary outcome [61] 0 0
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
Timepoint [61] 0 0
Days 1-7 (SDs 81-87, respectively)
Primary outcome [62] 0 0
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
Timepoint [62] 0 0
Days 1-10 (SDs 81-90, respectively)
Primary outcome [63] 0 0
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
Timepoint [63] 0 0
Days 1, 2, 4, 11, 12, and 13 (SDs 124, 125, 127, 134, 135, and 136, respectively)
Primary outcome [64] 0 0
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
Timepoint [64] 0 0
Baseline (Day -1); Days 1-3
Primary outcome [65] 0 0
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
Timepoint [65] 0 0
Baseline (Day -1; SD 37); Days 1-3 and 7-10 (SDs 38-40 and 44-47, respectively)
Primary outcome [66] 0 0
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
Timepoint [66] 0 0
Baseline (Day -1; SD 80); Days 1-7 (SDs 81-87, respectively)
Primary outcome [67] 0 0
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
Timepoint [67] 0 0
Baseline (Day -1; SD 80); Days 1-10 (SDs 81-90, respectively)
Primary outcome [68] 0 0
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
Timepoint [68] 0 0
Baseline (Day -1; SD 123); Days 1-3 (SDs 124-126, respectively); Days 10-13 (SDs 133-136, respectively)
Secondary outcome [1] 0 0
Number of elderly participants with any non-serious and any serious adverse event
Timepoint [1] 0 0
up to Day 15
Secondary outcome [2] 0 0
Number of elderly participants with an adverse event of the indicated causality and severity
Timepoint [2] 0 0
up to Day 15
Secondary outcome [3] 0 0
Number of participants with abnormal, clinically significant hematology and clinical chemistry parameters at the indicted time points in Part A for elderly participants
Timepoint [3] 0 0
Baseline (Day -1); Days 3, 5, 7, and 15 (Follow-up)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline (Day -1); Days 1-3; Day 5; Day 7; Day 15 (Follow-up)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline (Day -1); Day 1; Day 3; Follow-up visit (Day 15)
Secondary outcome [6] 0 0
Number of elderly participants with an infusion site reaction
Timepoint [6] 0 0
up to Day 15
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Days 1-3
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Days 1-3
Secondary outcome [9] 0 0
Mean AUC0-24, AUC0-t, and AUC0-8 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
Timepoint [9] 0 0
Days 1-3
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Days 1-3
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Days 1-3
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Days 1-3
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Days 1-3
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Days 1-3
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Days 1-3
Secondary outcome [16] 0 0
Number of elderly participants using concomitant medications
Timepoint [16] 0 0
up to Day 15

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Entasis Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/show/NCT02971423
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason Lickliter
Address 0 0
Nucleus Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications