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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases

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

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: Placebo
matching placebo infusion
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Timepoint [24] 0 0
Days 1-3
Primary outcome [25] 0 0
Mean Tmax in blood at the indicated time points in Part B
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
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
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
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
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
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
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
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
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
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
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
Timepoint [36] 0 0
Days 1-3
Primary outcome [37] 0 0
Mean Kel in blood at the indicated time points in Part B
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
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
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
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
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
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
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
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
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
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
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
Timepoint [48] 0 0
Days 1-3
Primary outcome [49] 0 0
Mean clearance in urine at the indicated time points in Part A
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
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
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
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
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
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
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
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
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
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
Timepoint [59] 0 0
Days 1-3
Primary outcome [60] 0 0
Mean VzVdss in blood at the indicated time points in Part B
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Sex
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
1/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2017
Sample size
Target
Accrual to date
Final
124
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/study/NCT02971423
Trial related presentations / 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. Erratum In: Antimicrob Agents Chemother. 2023 Jun 15;67(6):e0047623. doi: 10.1128/aac.00476-23.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02971423