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A Study to Evaluate the Safety and Pharmacokinetics (PK, the Measure of How the Human Body Processes a Substance) of ETX0282 When Administered Orally to Healthy Participants

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ClinicalTrials.gov Identifier: NCT03491748
Recruitment Status : Recruiting
First Posted : April 9, 2018
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
Entasis Therapeutics

Brief Summary:
This research project is being conducted to investigate the safety, tolerability, and pharmacokinetics (PK) of a single ascending dose (SAD) and multiple ascending doses (MAD) of oral ETX0282 when administered alone and in combination with cefpodoxime proxetil in healthy adult participants.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: ETX0282 Drug: Cefpodoxime proxetil Drug: Placebo Phase 1

Detailed Description:

This Phase 1, single-center, double-blind, randomized, placebo-controlled study will be conducted to:

  • Determine the safety and tolerability of oral ETX0282 when administered as a SAD and MAD to healthy participants;
  • Determine the safety and tolerability of oral ETX0282 when administered as a single oral dose in combination with cefpodoxime proxetil to healthy participants;
  • Characterize the PK in plasma and in urine of ETX0282 and ETX1317 following administration of single and multiple oral doses of ETX0282 in healthy participants; and
  • Determine the PK profile in plasma and in urine of ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of single oral doses of ETX0282 and cefpodoxime proxetil alone and when ETX0282 is co-administered with cefpodoxime proxetil at the same time as single oral doses in healthy participants.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral ETX0282 Administered in Healthy Subjects
Actual Study Start Date : March 16, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A (SAD): Cohort 1, 100 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and pharmacokinetics (PK) of a single ascending dose (SAD) of oral ETX0282. Participants will be treated with a single oral dose of 100 milligrams (mg) ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part A (SAD): Cohort 2, 200 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part A (SAD): Cohort 3, 400 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 400 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part A (SAD): Cohort 4, 800 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part A (SAD): Cohort 5, 1600 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 1600 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part A (SAD): Cohort 6 (Elderly), 800 mg ETX0282/Placebo
Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Elderly participants (aged 65 years or older) will be treated with a single oral dose of 800 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part B (Food Effect): Cohort 7, 800 mg ETX0282/Placebo
Part B of the study will explore the effect of food on oral ETX0282. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo (Day 1) while fasted and with a single oral dose of 800 mg ETX0282 or placebo (Day 4) with a high-fat meal. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post fed state dose assessments (Day 7).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part C (MAD): Cohort 8, 100 mg ETX0282/Placebo
Part C of the study will explore the safety, tolerability, and PK of multiple ascending doses (MAD) of oral ETX0282. Participants will be treated with a single oral dose of 100 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed twice daily (BID) beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 100 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part C (MAD): Cohort 9, 200 mg ETX0282/Placebo
Part C of the study will explore the safety, tolerability, and PK of MAD of oral ETX0282. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed BID beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part C (MAD): Cohort 10, 400 mg ETX0282/Placebo
Part C of the study will explore the safety, tolerability, and PK of MAD of oral ETX0282. Participants will be treated with a single oral dose of 400 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed BID beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 400 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part C (MAD): Cohort 11, 800 mg ETX0282/Placebo
Part C of the study will explore the safety, tolerability, and PK of MAD of oral ETX0282. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed BID beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).
Drug: ETX0282
Oral Gelatin capsules

Drug: Placebo
Oral Gelatin capsules

Experimental: Part D: Cohort 12, ETX0282/Placebo plus Cefpodoxime Proxetil
Part D of the study will explore the safety, tolerability, and PK of oral ETX0282 when administered as a single oral dose in combination with cefpodoxime proxetil tablets to healthy participants in a fasted state. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo in a fasted state on Day 1, with a single oral dose of 400 mg cefpodoxime proxetil in a fasted state on Day 4, and with a single oral dose of 800 mg ETX0282 or placebo plus a single oral dose of 400 mg cefpodoxime proxetil dosed at the same time in a fasted state on Day 7. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 7 dose assessments (Day 10).
Drug: ETX0282
Oral Gelatin capsules

Drug: Cefpodoxime proxetil
Oral tablets

Drug: Placebo
Oral Gelatin capsules

Experimental: Part E: Cohort 13, ETX0282/Placebo plus Cefpodoxime Proxetil
Part E of the study will explore the safety and tolerability of oral ETX0282 when administered as a multiple-dose combination with cefpodoxime proxetil tablets to healthy participants. Participants will be treated with an oral dose of 800 mg ETX0282 or placebo plus an oral dose of 400 mg cefpodoxime proxetil BID through Day 10, and once a day on Day 11. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 11 dose assessments (Day 14).
Drug: ETX0282
Oral Gelatin capsules

Drug: Cefpodoxime proxetil
Oral tablets

Drug: Placebo
Oral Gelatin capsules




Primary Outcome Measures :
  1. Number of participants with any non-serious adverse event [ Time Frame: Up to 14 days after the last dose of study drug (Study Day [SD] 256) ]
  2. Number of participants with any serious adverse event [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
  3. Number of participants with an adverse event of the indicated causality and severity [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
  4. Part A: Number of participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1) up to Day 15±2 (Follow-up) ]
  5. Part B: Number of participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1; SD 74) up to Day 18±2 (SD 92±2; Follow-up) ]
  6. Part C: Number of participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1; SD 123) up to Day 22±2 (SD 145±2; Follow-up) ]
  7. Part D: Number of participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1; SD 176) up to Day 21±2 (SD 197±2; Follow-up) ]
  8. Part E: Number of participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1; SD 228) up to Day 25±2 (SD 253±2; Follow-up) ]
  9. Part A: Number of participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1) up to Day 15±2 (Follow-up) ]
  10. Part B: Number of participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1; SD 74) up to Day 18±2 (SD 92±2; Follow-up) ]
  11. Part C: Number of participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1; SD 123) up to Day 22±2 (SD 145±2; Follow-up) ]
  12. Part D: Number of participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1; SD 176) up to Day 21±2 (SD 197±2; Follow-up) ]
  13. Part E: Number of participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1; SD 228) up to Day 25±2 (SD 253±2; Follow-up) ]
  14. Part A: Number of participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1) up to Day 15±2 (Follow-up) ]
  15. Part B: Number of participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1; SD 74) up to Day 18±2 (SD 92±2; Follow-up) ]
  16. Part C: Number of participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1; SD 123) up to Day 22±2 (SD 145±2; Follow-up) ]
  17. Part D: Number of participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1; SD 176) up to Day 21±2 (SD 197±2; Follow-up) ]
  18. Part E: Number of participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1; SD 228) up to Day 25±2 (SD 253±2; Follow-up) ]
  19. Part A: Mean peak plasma concentration (Cmax) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  20. Part A: Mean plasma concentration at time t (Ct) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  21. Part A: Mean time to peak plasma concentration (Tmax) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  22. Part A: Mean area under the concentration-time curve from time 0 to 24 hours (AUC0-24) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), and 24 (Day 2) hours postdose ]
  23. Part A: Mean area under the concentration-time curve from time 0 to the last time point evaluated (AUC0-t) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  24. Part A: Mean area under the concentration-time curve from time 0 and extrapolated to infinity (AUC0-∞) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  25. Part A: Mean elimination rate constant (Kel) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  26. Part A: Mean elimination half-life (t½) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  27. Part A: Mean clearance (CL) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  28. Part A: Mean volume of distribution (Vdss) of ETX0282 and ETX1317 in blood in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  29. Part A: Mean cumulative excretion of unchanged ETX0282 and ETX1317 in urine (Ae) in Cohorts 1 to 5 [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  30. Part A: Mean urinary clearance (CLR) of ETX0282 and ETX1317 in Cohorts 1 to 5 [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  31. Part A: Mean fraction of the administered dose of ETX0282 and ETX1317 that is excreted unchanged in the urine (fe) in Cohorts 1 to 5 [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  32. Part A: Mean dose proportionality of ETX0282 and ETX1317 in Cohorts 1 to 5 [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  33. Part C: Mean Cmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  34. Part C: Mean Ct of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  35. Part C: Mean Tmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  36. Part C: Mean AUC0-24 of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  37. Part C: Mean AUC0-t of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  38. Part C: Mean AUC0-∞ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  39. Part C: Mean AUC from time 0 to the end of the dosing period (AUC0-tau) of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  40. Part C: Mean accumulation ratio (R0) of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  41. Part C: Mean Kel of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  42. Part C: Mean t½ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  43. Part C: Mean CL of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  44. Part C: Mean Vdss of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  45. Part C: Mean Ae of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 8-11 (SDs 124-127 and 131-134): prior to dosing (-6 to 0 hours; first and last doses) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  46. Part C: Mean CLR of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 8-11 (SDs 124-127 and 131-134): prior to dosing (-6 to 0 hours; first and last doses) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  47. Part C: Mean fe of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 8-11 (SDs 124-127 and 131-134): prior to dosing (-6 to 0 hours; first and last doses) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  48. Part C: Mean dose proportionality of ETX0282 and ETX1317 [ Time Frame: Days 1-3, 5, and 8 (SDs 124-126, 128, and 131): predose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, 5, and 8 (SDs 126, 128, and 131); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post last dose ]
  49. Part D: Mean Cmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  50. Part D: Mean Ct of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  51. Part D: Mean Tmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  52. Part D: Mean AUC0-24 of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose ]
  53. Part D: Mean AUC0-t of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  54. Part D: Mean AUC0-∞ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  55. Part D: Mean Kel of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  56. Part D: Mean t½ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  57. Part D: Mean CL of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  58. Part D: Mean Vdss of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  59. Part D: Mean Ae of ETX0282 and ETX1317 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  60. Part D: Mean CLR of ETX0282 and ETX1317 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  61. Part D: Mean fe of ETX0282 and ETX1317 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  62. Part D: Mean dose proportionality of ETX0282 and ETX1317 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  63. Part E: Mean Cmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  64. Part E: Mean Ct of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  65. Part E: Mean Tmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  66. Part E: Mean AUC0-24 of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  67. Part E: Mean AUC0-t of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  68. Part E: Mean AUC0-∞ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  69. Part E: Mean AUC0-tau of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  70. Part E: Mean R0 of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  71. Part E: Mean Kel of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  72. Part E: Mean t½ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  73. Part E: Mean CL of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  74. Part E: Mean Vdss of ETX0282 and ETX1317 in blood [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  75. Part E: Mean Ae of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  76. Part E: Mean CLR of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  77. Part E: Mean fe of ETX0282 and ETX1317 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  78. Part E: Mean dose proportionality of ETX0282 and ETX1317 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  79. Part D: Mean Cmax of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  80. Part D: Mean Ct of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  81. Part D: Mean Tmax of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  82. Part D: Mean AUC0-24 of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose ]
  83. Part D: Mean AUC0-t of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  84. Part D: Mean AUC0-∞ of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  85. Part D: Mean Kel of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  86. Part D: Mean t½ of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  87. Part D: Mean CL of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  88. Part D: Mean Vdss of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  89. Part D: Mean Ae of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  90. Part D: Mean CLR of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  91. Part D: Mean fe of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  92. Part D: Mean dose proportionality of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-10 (SDs 177-186): predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours postdose ]
  93. Part E: Mean Cmax of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  94. Part E: Mean Ct of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  95. Part E: Mean Tmax of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  96. Part E: Mean AUC0-24 of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  97. Part E: Mean AUC0-t of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  98. Part E: Mean AUC0-∞ of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  99. Part E: Mean AUC0-tau of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  100. Part E: Mean R0 of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  101. Part E: Mean Kel of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  102. Part E: Mean t½ of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  103. Part E: Mean CL of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  104. Part E: Mean Vdss of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  105. Part E: Mean Ae of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  106. Part E: Mean CLR of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  107. Part E: Mean fe of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  108. Part E: Mean dose proportionality of cefpodoxime proxetil and cefpodoxime following administration of cefpodoxime proxetil as a single oral dose either alone or in combination with ETX0282 [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]

Secondary Outcome Measures :
  1. Number of elderly participants with any non-serious adverse event [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
  2. Number of elderly participants with any serious adverse event [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
  3. Number of elderly participants with an adverse event of the indicated causality and severity [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
  4. Part A: Number of elderly participants with abnormal, clinically significant hematology, clinical chemistry, and urinalysis laboratory values at the indicated time points [ Time Frame: Screening (Day -1); Days 2, 3, 4, 7, and 15±2 (Follow-up) ]
  5. Part A: Number of elderly participants with abnormal, clinically significant vital sign values at the indicated time points [ Time Frame: Screening (Day -1); Days 2, 3, 4, 7, and 15±2 (Follow-up) ]
  6. Part A: Number of elderly participants with abnormal, clinically significant electrocardiogram values at the indicated time points [ Time Frame: Screening (Day -1); Days 1-7; Day 15±2 (Follow-up) ]
  7. Number of participants who received concomitant medications [ Time Frame: Up to 14 days after the last dose of study drug (SD 256) ]
    Concomitant medications will be coded using the World Health Organization Drug Dictionary. The incidence of participants taking each medication by Anatomical Therapeutic Chemical second and fourth level categories (pharmacological or therapeutic group) will be presented.

  8. Part A: Mean Cmax of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  9. Part A: Mean Ct of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  10. Part A: Mean Tmax of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  11. Part A: Mean AUC0-24 of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), and 24 (Day 2) hours postdose ]
  12. Part A: Mean AUC0-t of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  13. Part A: Mean AUC0-∞ of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  14. Part A: Mean Kel of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  15. Part A: Mean t½ of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  16. Part A: Mean CL of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  17. Part A: Mean Vdss of ETX0282 and ETX1317 in blood of elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  18. Part A: Mean Ae of ETX0282 and ETX1317 for elderly participants (Cohort 6) [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  19. Part A: Mean CLR of ETX0282 and ETX1317 in urine for elderly participants (Cohort 6) [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  20. Part A: Mean fe of ETX0282 and ETX1317 for elderly participants (Cohort 6) [ Time Frame: Prior to dosing (-6 to 0 hours; Day 1); 0 to 8 (Day 1), 8 to 24 (Day 2), 24 to 48 (Day 3), and 48 to 72 (Day 4) hours postdose ]
  21. Part A: Mean dose proportionality of ETX0282 and ETX1317 for elderly participants (Cohort 6) [ Time Frame: Predose (0); 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 (Day 1), 24 (Day 2), 48 (Day 3), and 72 (Day 4) hours postdose ]
  22. Part B: Mean Cmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  23. Part B: Mean Ct of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  24. Part B: Mean Tmax of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  25. Part B: Mean AUC0-24 of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, and 24 hours postdose ]
  26. Part B: Mean AUC0-t of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  27. Part B: Mean AUC0-∞ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  28. Part B: Mean Kel of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  29. Part B: Mean t½ of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  30. Part B: Mean CL of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  31. Part B: Mean Vdss of ETX0282 and ETX1317 in blood [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  32. Part B: Mean Ae of ETX0282 and ETX1317 [ Time Frame: Days 1-7 (SDs 75-81): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  33. Part B: Mean CLR of ETX0282 and ETX1317 [ Time Frame: Days 1-7 (SDs 75-81): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  34. Part B: Mean fe of ETX0282 and ETX1317 [ Time Frame: Days 1-7 (SDs 75-81): prior to dosing (-6 to 0 hours) and at 0-8, 8-24, 24-48, and 48-72 hours postdose ]
  35. Part B: Mean dose proportionality of ETX0282 and ETX1317 [ Time Frame: Days 1-7 (SDs 75-81): predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48, and 72 hours postdose ]
  36. Part E: Mean Cmax of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  37. Part E: Mean Ct of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  38. Part E: Mean Tmax of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  39. Part E: Mean AUC0-24 of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  40. Part E: Mean AUC0-t of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  41. Part E: Mean AUC0-∞ of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  42. Part E: Mean AUC0-tau of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  43. Part E: Mean R0 of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  44. Part E: Mean Kel of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  45. Part E: Mean t½ of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  46. Part E: Mean CL of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  47. Part E: Mean Vdss of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]
  48. Part E: Mean Ae of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  49. Part E: Mean CLR of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  50. Part E: Mean fe of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1-4 and 11-14 (SDs 229-231 and 239-242): prior to dosing (-6 to 0 hours; first and last dose) and at 0-8, 8-24, 24-48, and 48-72 hours post first and last dose ]
  51. Part E: Mean dose proportionality of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil [ Time Frame: Days 1, 2, 4, 7, 9, and 11 (SDs 229, 230, 232, 235, 237, and 239): prior to the first dose; at trough on Days 2, 4, 7, 9, and 11 (SDs 230, 232, 235, 237, and 239); and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the last dose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 18 to 55 years (inclusive). In addition, for Cohort 6 in Part A, 8 participants ≥65 years of age will be enrolled.
  • Be in general good health without 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) ≥18.0 kilograms per meters squared (kg/m^2) and ≤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, hepatitis C virus antibody, and human immunodeficiency virus at Screening; and drugs of abuse, alcohol predose on Day -1
  • Female participants must be of non-childbearing potential (postmenopausal or with evidence of tubal ligation) or using a medically acceptable (highly effective method) 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. Men should not donate sperm during the study or for 90 days after the final dose of study medication.

Exclusion Criteria:

  • History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antimicrobial (e.g., penicillin or cephalosporin)
  • History of hypersensitivity or severe allergic reaction of any type to medications, bee stings, food, or environmental factors. A severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema.
  • 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 were at least 30 days between the last dose in a prior study and dose administration in 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
  • Surgery within 30 days before study enrolment
  • Unwillingness or inability to comply with the study protocol for any other reason

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03491748


Contacts
Contact: Jason Lickliter +61 390768609 j.lickliter@nucleusnetwork.com

Locations
Australia, Victoria
Nucleus Network Recruiting
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Entasis Therapeutics

Responsible Party: Entasis Therapeutics
ClinicalTrials.gov Identifier: NCT03491748     History of Changes
Other Study ID Numbers: CS0282-2017-0001
1010452 ( Other Identifier: INC Research )
First Posted: April 9, 2018    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Entasis Therapeutics:
Pharmacokinetics
ETX0282
Single Ascending Dose
Multiple Ascending Doses
ETX1317
Cefpodoxime Proxetil
Cefpodoxime
Enterobacteriaceae Infections

Additional relevant MeSH terms:
Cefpodoxime
Cefpodoxime proxetil
Ceftizoxime
Anti-Bacterial Agents
Anti-Infective Agents