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Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01595438
Collaborator
Forest Laboratories (Industry)
598
Enrollment
84
Locations
2
Arms
22
Duration (Months)
7.1
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

Condition or Disease Intervention/Treatment Phase
  • Drug: Ceftazidime - Avibactam ( CAZ-AVI)
  • Drug: Doripenem
  • Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
  • Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
 Phase 3

Detailed Description

A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Study Design

Study Type:
Interventional
Actual Enrollment :
598 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults
Study Start Date :
Oct 1, 2012
Actual Primary Completion Date :
Aug 1, 2014
Actual Study Completion Date :
Aug 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ceftazidime - Avibactam ( CAZ-AVI)

IV treatment

Drug: Ceftazidime - Avibactam ( CAZ-AVI)
Ceftazidime 2000 mg and 500 mg of avibactam. Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes

Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement
Active Comparator: Doripenem

IV treatment

Drug: Doripenem
500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes

Drug: Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Drug: or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)
Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Outcome Measures

Primary Outcome Measures

  1. Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test [At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.]

    Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

  2. Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

  3. Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.

Secondary Outcome Measures

  1. Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  2. Per-patient Microbiological Response at LFU (mMITT Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at LFU

  3. Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  4. Per-patient Microbiological Response at TOC (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at TOC

  5. Per-patient Microbiological Response at LFU (ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at LFU

  6. Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a favorable per-patient microbiological response at EOT (IV)

  7. Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at TOC

  8. Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a favorable per patient microbiological response at LFU

  9. Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  10. Investigator Determined Clinical Response at TOC (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  11. Investigator Determined Clinical Response at LFU (mMITT Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  12. Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  13. Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  14. Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  15. Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  16. Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  17. Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  18. Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  19. Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  20. Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.

  21. Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  22. Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  23. Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.

  24. Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set.

  25. Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set.

  26. Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set.

  27. Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set) [Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.]

    Time to first defervescence while on IV study therapy in patients in the mMITT analysis set who have fever at study entry.

  28. Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set) [Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.]

    Time to first defervescence while on IV study therapy in patients in the ME at TOC analysis set who have fever at study entry.

  29. Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set) [Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.]

    Time to first defervescence while on IV study therapy in patients in the Extended ME at TOC analysis set who have fever at study entry.

  30. Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set) [Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.]

    Time to first defervescence while on IV study therapy in patients in the CE at TOC analysis set who have fever at study entry.

  31. Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set) [At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set

  32. Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set

  33. Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set

  34. Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set) [At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set

  35. Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set

  36. Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set

  37. Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set

  38. Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set

  39. Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set

  40. Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set) [At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set for blood only

  41. Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set for blood only

  42. Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set for blood only

  43. Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set) [At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set for blood only

  44. Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set for blood only

  45. Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set for blood only

  46. Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set) [At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy]

    Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set for blood only

  47. Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set for blood only

  48. Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set) [At LFU visit. LFU visit is 45 to 52 days from Randomization.]

    Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set for blood only

  49. Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the mMITT analysis set

  50. Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the Extended ME at TOC analysis set

  51. Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the ME at TOC analysis set

  52. Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the mMITT analysis set

  53. Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the Extended ME at TOC analysis set

  54. Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set) [At TOC visit. TOC visit is 21 to 25 days from Randomization]

    Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the ME at TOC analysis set

  55. Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set) [within 15 minutes before/after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  56. Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set) [Between 30 to 90 minutes after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  57. Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set) [Between 300 to 360 minutes after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  58. Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set) [within 15 minutes before/after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  59. Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set) [Between 30 to 90 minutes after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

  60. Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set) [Between 300 to 360 minutes after dose]

    Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • 18 to 90 years of age inclusive

  • Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after

  • Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)

  • Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis.

Exclusion Criteria:

  • Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem

  • Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI

  • Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant

  • Patient is immunocompromised

  • Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Sylmar California United States
2 Research Site Royal Oak Michigan United States
3 Research Site Lima Ohio United States
4 Research Site Cordoba Argentina
5 Research Site Corrientes Argentina
6 Research Site Córdoba Argentina
7 Research Site Mendoza Argentina
8 Research Site Santa Fe Argentina
9 Research Site Belo Horizonte Brazil
10 Research Site Campinas/SP Brazil
11 Research Site Salvador Brazil
12 Research Site São José do Rio Preto - SP Brazil
13 Research Site São Paulo Brazil
14 Research Site Vila Clementino Brazil
15 Research Site Pleven Bulgaria
16 Research Site Ruse Bulgaria
17 Research Site Sofia Bulgaria
18 Research Site Zagreb Croatia
19 Research Site Kyjov Czechia
20 Research Site Opava Czechia
21 Research Site Jena Germany
22 Research Site Wuppertal Germany
23 Research Site Athens Greece
24 Research Site Budapest Hungary
25 Research Site Nagykanizsa Hungary
26 Research Site Nyíregyháza Hungary
27 Research Site Zalaegerszeg Hungary
28 Research Site Jerusalem Israel
29 Research Site Petach-Tikva Israel
30 Research Site Safed Israel
31 Research Site Fukuoka-shi Japan
32 Research Site Koshigaya-shi Japan
33 Research Site Kyoto-shi Japan
34 Research Site Nagoya-shi Japan
35 Research Site Nara-shi Japan
36 Research Site Oita-shi Japan
37 Research Site Sendai-shi Japan
38 Research Site Sunto-gun Japan
39 Research Site Tokushima-shi Japan
40 Research Site Ueda-shi Japan
41 Research Site Utsunomiya-shi Japan
42 Research Site Busan Korea, Republic of
43 Research Site Seoul Korea, Republic of
44 Research Site Wonju Korea, Republic of
45 Research Site Guadalajara, Jalisco Mexico
46 Research Site Inowrocław Poland
47 Research Site Krakow Poland
48 Research Site Warszawa Poland
49 Research Site Lisboa Portugal
50 Research Site Brasov Romania
51 Research Site Bucharest Romania
52 Research Site Bucuresti Romania
53 Research Site Cluj Romania
54 Research Site Craiova Romania
55 Research Site Iasi Romania
56 Research Site Arkhangelsk Russian Federation
57 Research Site Krasnodar Russian Federation
58 Research Site Moscow Russian Federation
59 Research Site Novosibirsk Russian Federation
60 Research Site Penza Russian Federation
61 Research Site Rostov-on-Don Russian Federation
62 Research Site Saratov Russian Federation
63 Research Site St. Petersburg Russian Federation
64 Research Site St.Petersburg Russian Federation
65 Research Site Vsevolozhsk Russian Federation
66 Research Site Belgrade Serbia
67 Research Site Kragujevac Serbia
68 Research Site Poprad Slovakia
69 Research Site Presov Slovakia
70 Research Site Trnava Slovakia
71 Research Site Zilina Slovakia
72 Research Site Chiayi Taiwan
73 Research Site Taipei Taiwan
74 Research Site Diyarbakir Turkey
75 Research Site Cherkasy Ukraine
76 Research Site Dnipropetrovsk Ukraine
77 Research Site Kharkiv Ukraine
78 Research Site Kyiv Ukraine
79 Research Site Lviv Ukraine
80 Research Site Mykolaiv Ukraine
81 Research Site Odesa Ukraine
82 Research Site Odessa Ukraine
83 Research Site Uzhhorod Ukraine
84 Research Site Zaporizhzhya Ukraine

Sponsors and Collaborators

  • Pfizer
  • Forest Laboratories

Investigators

  • Study Director: Paul Newell, MBBS, MRCP, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01595438
Other Study ID Numbers:
  • D4280C00002
  • 2011-005721-43
First Posted:
May 10, 2012
Last Update Posted:
Sep 6, 2017
Last Verified:
Aug 1, 2017
Keywords provided by Pfizer
Ceftazidime, Avibactam, Doripenem, Ciprofloxacin, sulfamethoxazole/trimethoprim, Anti-Infective Agents, Complicated Urinary Tract Infection,Acute Pyelonephritis
Additional relevant MeSH terms:
Infections
Communicable Diseases
Urinary Tract Infections
Pyelonephritis
Ciprofloxacin
Ceftazidime
Doripenem
Avibactam
Trimethoprim, Sulfamethoxazole Drug Combination
Trimethoprim
Sulfamethoxazole

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail The results presented in these forms represent the combined data base of the two identical protocols D4280C00002 and D4280C00004. The protocol D4280C00002 has a total of 522 randomized patients and the protocol D4280C00004 has a total of 511 randomized patients which adds up to a combined total of 1033 patients.
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Period Title: Overall Study
STARTED 516 517
COMPLETED 473 476
NOT COMPLETED 43 41

Baseline Characteristics

Arm/Group Title CAZ-AVI Doripenem Total
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group Total of all reporting groups
Overall Participants 511 509 1020
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
51.6
(19.76)
52.3
(18.83)
52.0
(19.29)
Age, Customized (Number) [Number]
18-45
192
37.6%
172
33.8%
364
35.7%
46-64
162
31.7%
177
34.8%
339
33.2%
65-74
79
15.5%
98
19.3%
177
17.4%
75-90
78
15.3%
62
12.2%
140
13.7%
Sex: Female, Male (Count of Participants)
Female
349
68.3%
357
70.1%
706
69.2%
Male
162
31.7%
152
29.9%
314
30.8%
Race/Ethnicity, Customized (Number) [Number]
American Indian Or Alaska Native
1
0.2%
3
0.6%
4
0.4%
Asian
48
9.4%
37
7.3%
85
8.3%
Black Or African American
1
0.2%
8
1.6%
9
0.9%
Other
40
7.8%
35
6.9%
75
7.4%
White
421
82.4%
426
83.7%
847
83%

Outcome Measures

1. Primary Outcome
Title Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test
Description Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Time Frame At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Symptomatic resolution
276
54%
276
54.2%
Symptom persistence
103
20.2%
124
24.4%
Indeterminate
14
2.7%
17
3.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of symptomatic resolution rates ≤ non-inferiority margin
Type of Statistical Test Non-Inferiority or Equivalence
Comments -12.5%
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of symp resolution rates
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
-2.39 to 10.42
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Description Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Favorable
280
54.8%
269
52.8%
Unfavorable
81
15.9%
109
21.4%
Indeterminate
32
6.3%
39
7.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable combined response rates ≤ non-inferiority margin
Type of Statistical Test Non-Inferiority or Equivalence
Comments -12.5%
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable combined resp rates
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
0.30 to 13.12
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
Title Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test
Description Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Favorable
304
59.5%
296
58.2%
Unfavorable
58
11.4%
83
16.3%
Indeterminate
31
6.1%
38
7.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: Difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates ≤ non-inferiority margin
Type of Statistical Test Non-Inferiority or Equivalence
Comments -12.5%
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 6.4
Confidence Interval (2-Sided) 95%
0.33 to 12.36
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set)
Description Number of patients with a favorable per-patient microbiological response at EOT (IV)
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Favorable
374
73.2%
395
77.6%
Unfavorable
1
0.2%
3
0.6%
Indeterminate
18
3.5%
19
3.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-2.70 to 3.56
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Per-patient Microbiological Response at LFU (mMITT Analysis Set)
Description Number of patients with a favorable per patient microbiological response at LFU
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Favorable
268
52.4%
254
49.9%
Unfavorable
83
16.2%
125
24.6%
Indeterminate
42
8.2%
38
7.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
0.68 to 13.81
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Description Number of patients with a favorable per-patient microbiological response at EOT (IV)
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at EOT (IV) (ME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 325 361
Favorable
324
63.4%
359
70.5%
Unfavorable
1
0.2%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.21 to 1.72
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Per-patient Microbiological Response at TOC (ME at TOC Analysis Set)
Description Number of patients with a favorable per patient microbiological response at TOC
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
Favorable
241
47.2%
225
44.2%
Unfavorable
45
8.8%
73
14.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
2.27 to 15.24
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Per-patient Microbiological Response at LFU (ME at LFU Analysis Set)
Description Number of patients with a favorable per patient microbiological response at LFU
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at LFU (ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 245 262
Favorable
182
35.6%
166
32.6%
Unfavorable
63
12.3%
96
18.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
2.86 to 18.85
Parameter Dispersion Type:
Value:
Estimation Comments
9. Secondary Outcome
Title Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Description Number of patients with a favorable per-patient microbiological response at EOT (IV)
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at EOT (IV) (EME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 336 371
Favorable
335
65.6%
369
72.5%
Unfavorable
1
0.2%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.17 to 1.68
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set)
Description Number of patients with a favorable per patient microbiological response at TOC
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (Extended ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
Favorable
243
47.6%
236
46.4%
Unfavorable
49
9.6%
75
14.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
0.88 to 13.74
Parameter Dispersion Type:
Value:
Estimation Comments
11. Secondary Outcome
Title Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set)
Description Number of patients with a favorable per patient microbiological response at LFU
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at LFU (Extended ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 251 272
Favorable
184
36%
173
34%
Unfavorable
67
13.1%
99
19.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 9.7
Confidence Interval (2-Sided) 95%
1.72 to 17.55
Parameter Dispersion Type:
Value:
Estimation Comments
12. Secondary Outcome
Title Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set)
Description Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Clinical cure
378
74%
407
80%
Clinical failure
5
1%
5
1%
Indeterminate
10
2%
5
1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-4.07 to 1.02
Parameter Dispersion Type:
Value:
Estimation Comments
13. Secondary Outcome
Title Investigator Determined Clinical Response at TOC (mMITT Analysis Set)
Description Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Clinical cure
355
69.5%
377
74.1%
Clinical failure
11
2.2%
24
4.7%
Indeterminate
27
5.3%
16
3.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-4.23 to 4.03
Parameter Dispersion Type:
Value:
Estimation Comments
14. Secondary Outcome
Title Investigator Determined Clinical Response at LFU (mMITT Analysis Set)
Description Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Clinical cure
335
65.6%
350
68.8%
Clinical failure
23
4.5%
39
7.7%
Indeterminate
35
6.8%
28
5.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-3.71 to 6.30
Parameter Dispersion Type:
Value:
Estimation Comments
15. Secondary Outcome
Title Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set)
Description Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at EOT (IV) (ME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 325 361
Clinical cure
318
62.2%
358
70.3%
Clinical failure
4
0.8%
2
0.4%
Indeterminate
3
0.6%
1
0.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.64 to 0.55
Parameter Dispersion Type:
Value:
Estimation Comments
16. Secondary Outcome
Title Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set)
Description Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC )
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
Clinical cure
277
54.2%
285
56%
Clinical failure
4
0.8%
13
2.6%
Indeterminate
5
1%
0
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-2.03 to 4.56
Parameter Dispersion Type:
Value:
Estimation Comments
17. Secondary Outcome
Title Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set)
Description Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at LFU (ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 245 262
Clinical cure
226
44.2%
236
46.4%
Clinical failure
15
2.9%
24
4.7%
Indeterminate
4
0.8%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-2.90 to 7.24
Parameter Dispersion Type:
Value:
Estimation Comments
18. Secondary Outcome
Title Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)
Description Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at EOT (IV) (Extended ME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 336 371
Clinical cure
327
64%
368
72.3%
Clinical failure
4
0.8%
2
0.4%
Indeterminate
5
1%
1
0.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-4.30 to 0.04
Parameter Dispersion Type:
Value:
Estimation Comments
19. Secondary Outcome
Title Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set)
Description Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (Extended ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
Clinical cure
283
55.4%
298
58.5%
Clinical failure
4
0.8%
13
2.6%
Indeterminate
5
1%
0
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-2.07 to 4.32
Parameter Dispersion Type:
Value:
Estimation Comments
20. Secondary Outcome
Title Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set)
Description Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at LFU (Extended ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 251 272
Clinical cure
232
45.4%
246
48.3%
Clinical failure
15
2.9%
24
4.7%
Indeterminate
4
0.8%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-2.94 to 6.91
Parameter Dispersion Type:
Value:
Estimation Comments
21. Secondary Outcome
Title Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set)
Description Number of patients with a clinical cure at EOT (IV). The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Clinically evaluable analysis set at EOT (IV) (CE at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 350 391
Clinical cure
346
67.7%
387
76%
Clinical failure
4
0.8%
4
0.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.99 to 1.61
Parameter Dispersion Type:
Value:
Estimation Comments
22. Secondary Outcome
Title Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set)
Description Number of patients with a clinical cure at TOC. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Clinically evaluable analysis set at TOC (CE at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 297 330
Clinical cure
289
56.6%
309
60.7%
Clinical failure
8
1.6%
21
4.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
0.41 to 7.16
Parameter Dispersion Type:
Value:
Estimation Comments
23. Secondary Outcome
Title Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set)
Description Number of patients with a clinical cure at LFU. The investigator should consider the entirety of the patient's clinical course and current status, including an evaluation of signs and symptoms (eg, fever, dysuria, costovertebral angle tenderness) and physical examination in order to classify the patient's clinical response.
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Clinically evaluable analysis set at LFU (CE at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 254 287
Clinical cure
235
46%
254
49.9%
Clinical failure
19
3.7%
33
6.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clinical cure rates
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
-1.00 to 9.05
Parameter Dispersion Type:
Value:
Estimation Comments
24. Secondary Outcome
Title Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Description Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
All patients - Clinical cure (n=75, 84)
67
13.1%
75
14.7%
Escherichia coli patients - Clin cure (n=36, 37)
33
6.5%
31
6.1%
Klebsiella pneumoniae patients-Clin cure(n=18,30)
17
3.3%
28
5.5%
Pseudomonas aeruginosa patients- Clin cure(n=7,6)
5
1%
6
1.2%
Enterobacter cloacae patients-Clin cure(n=7,6)
5
1%
5
1%
Proteus mirabilis patients - Clin cure (n=2, 5)
2
0.4%
5
1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clin cure rates in All patients
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-10.4 to 10.1
Parameter Dispersion Type:
Value:
Estimation Comments
25. Secondary Outcome
Title Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Description Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC(ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
All patients - Clinical cure (n=48, 57)
47
9.2%
55
10.8%
Escherichia coli patients-Clin cure (n=23,27)
22
4.3%
25
4.9%
Klebsiella pneumoniae patients-Clin cure(n=14, 22)
14
2.7%
22
4.3%
Pseudomonas aeruginosa patients-Clin cure(n=1, 2)
1
0.2%
2
0.4%
Enterobacter cloacae patients-Clin cure(n=5,5)
5
1%
5
1%
Proteus mirabilis patients - Clin cure (n=0, 2)
0
0%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clin cure rates in All patients
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-7.8 to 10.2
Parameter Dispersion Type:
Value:
Estimation Comments
26. Secondary Outcome
Title Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Description Clinical cure at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set. Includes patients infected by at least one ceftazidime-resistant Gram-negative pathogen.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC(Extended ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
All patients - Clinical cure (n=51, 63)
50
9.8%
61
12%
Escherichia coli patients - Clin cure (n=23, 27)
22
4.3%
25
4.9%
Klebsiella pneumoniae patients-Clin cure(n=15, 23)
15
2.9%
23
4.5%
Pseudomonas aeruginosa patients-Clin cure(n=3,6)
3
0.6%
6
1.2%
Enterobacter cloacae patients-Clin cure(n=5,5)
5
1%
5
1%
Proteus mirabilis patients - Clin cure (n=0, 2)
0
0%
2
0.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of clinical cure rates in All patients with a ceftazidime-resistant Gram-negative pathogen
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of clin cure rates in All patients
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-7.5 to 9.2
Parameter Dispersion Type:
Value:
Estimation Comments
27. Secondary Outcome
Title Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)
Description Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the mMITT analysis set.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 75 84
Favorable
47
9.2%
51
10%
Unfavorable
19
3.7%
27
5.3%
Indeterminate
9
1.8%
6
1.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-13.18 to 16.89
Parameter Dispersion Type:
Value:
Estimation Comments
28. Secondary Outcome
Title Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)
Description Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the ME at TOC analysis set.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC(ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 48 57
Favorable
35
6.8%
37
7.3%
Unfavorable
13
2.5%
20
3.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
-10.03 to 25.21
Parameter Dispersion Type:
Value:
Estimation Comments
29. Secondary Outcome
Title Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)
Description Favorable per-patient microbiological response at the TOC visit for patients infected with a ceftazidime resistant pathogen in the Extended ME at TOC analysis set.
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC(Extended ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 51 63
Favorable
37
7.2%
41
8.1%
Unfavorable
14
2.7%
22
4.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments Confidence interval of the difference (CAZ-AVI treatment group minus Doripenem treatment group) of favorable response rates
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Diff of favorable response rates
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
-9.91 to 24.01
Parameter Dispersion Type:
Value:
Estimation Comments
30. Secondary Outcome
Title Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set)
Description Time to first defervescence while on IV study therapy in patients in the mMITT analysis set who have fever at study entry.
Time Frame Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Number of patients with fever (>38°C) at baseline
157
30.7%
150
29.5%
Number afebrile at the time of the last obs
155
30.3%
143
28.1%
Number censored at the time of the last obs
2
0.4%
7
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: No difference in time to first defervescence between treatment groups.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.038
Comments
Method Log Rank
Comments
31. Secondary Outcome
Title Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set)
Description Time to first defervescence while on IV study therapy in patients in the ME at TOC analysis set who have fever at study entry.
Time Frame Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC(ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
Number of patients with fever (>38°C) at baseline
124
24.3%
108
21.2%
Number afebrile at the time of the last obs
124
24.3%
105
20.6%
Number censored at the time of the last obs
0
0%
3
0.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: No difference in time to first defervescence between treatment groups.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.129
Comments
Method Log Rank
Comments
32. Secondary Outcome
Title Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set)
Description Time to first defervescence while on IV study therapy in patients in the Extended ME at TOC analysis set who have fever at study entry.
Time Frame Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC(Extended ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
Number of patients with fever (>38°C) at baseline
124
24.3%
111
21.8%
Number afebrile at the time of the last obs
124
24.3%
108
21.2%
Number censored at the time of the last obs
0
0%
3
0.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: No difference in time to first defervescence between treatment groups.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.080
Comments
Method Log Rank
Comments
33. Secondary Outcome
Title Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set)
Description Time to first defervescence while on IV study therapy in patients in the CE at TOC analysis set who have fever at study entry.
Time Frame Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.

Outcome Measure Data

Analysis Population Description
Clinically evaluable analysis set at TOC(CE at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 297 330
Number of patients with fever (>38°C) at baseline
123
24.1%
118
23.2%
Number afebrile at the time of the last obs
122
23.9%
113
22.2%
Number censored at the time of the last obs
1
0.2%
5
1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Doripenem
Comments H0: No difference in time to first defervescence between treatment groups.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.155
Comments
Method Log Rank
Comments
34. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set
Time Frame At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=292, 306)
280
293
Klebsiella pneumoniae - Favorable (n=44, 56)
41
51
Proteus mirabilis - Favorable (n=17, 13)
16
11
Enterobacter cloacae - Favorable (n= 11,13)
9
13
Pseudomonas aeruginosa - Favorable (n=18, 20)
17
18
35. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=292, 306)
229
220
Klebsiella pneumoniae - Favorable (n=44, 56)
33
35
Proteus mirabilis - Favorable (n=17, 13)
16
9
Enterobacter cloacae - Favorable (n= 11,13)
6
9
Pseudomonas aeruginosa - Favorable (n=18, 20)
12
15
36. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=292, 306)
198
189
Klebsiella pneumoniae - Favorable (n=44, 56)
32
30
Proteus mirabilis - Favorable (n=17, 13)
16
6
Enterobacter cloacae - Favorable (n= 11,13)
6
9
Pseudomonas aeruginosa - Favorable (n=18, 20)
9
13
37. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set
Time Frame At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at EOT (IV) (EME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 336 371
Escherichia coli - Favorable (n=250, 274)
250
274
Klebsiella pneumoniae - Favorable (n=34, 49)
34
48
Proteus mirabilis - Favorable (n=13, 11)
13
11
Enterobacter cloacae - Favorable (n= 9, 12)
9
12
Pseudomonas aeruginosa - Favorable (n=18, 18)
17
17
38. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (EME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
Escherichia coli - Favorable (n=214, 226)
180
176
Klebsiella pneumoniae - Favorable (n=32, 42)
26
29
Proteus mirabilis - Favorable (n=14, 7)
14
4
Enterobacter cloacae - Favorable (n= 7, 11)
5
8
Pseudomonas aeruginosa - Favorable (n=13, 18)
8
13
39. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at LFU (EME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 251 272
Escherichia coli - Favorable (n=179, 198)
129
131
Klebsiella pneumoniae - Favorable (n=31, 36)
24
19
Proteus mirabilis - Favorable (n=11,5)
11
1
Enterobacter cloacae - Favorable (n= 7, 11)
5
8
Pseudomonas aeruginosa - Favorable (n=12, 16)
7
9
40. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at EOT (IV) (ME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 325 361
Escherichia coli - Favorable (n=249, 270)
249
270
Klebsiella pneumoniae - Favorable (n=33, 48)
33
47
Proteus mirabilis - Favorable (n=13,11)
13
11
Enterobacter cloacae - Favorable (n= 9, 12)
9
12
Pseudomonas aeruginosa - Favorable (n=10, 15)
9
14
41. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
Escherichia coli - Favorable (n=214, 221)
180
171
Klebsiella pneumoniae - Favorable (n=31, 41)
25
28
Proteus mirabilis - Favorable (n=14, 7)
14
4
Enterobacter cloacae - Favorable (n= 7, 11)
5
8
Pseudomonas aeruginosa - Favorable (n=9, 13)
7
9
42. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at LFU (ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 245 262
Escherichia coli - Favorable (n=179, 194)
129
127
Klebsiella pneumoniae - Favorable (n=30, 35)
23
18
Proteus mirabilis - Favorable (n=11,5)
11
1
Enterobacter cloacae - Favorable (n= 7, 11)
5
8
Pseudomonas aeruginosa - Favorable (n=8, 13)
6
8
43. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the mMITT analysis set for blood only
Time Frame At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=32, 28)
31
28
Klebsiella pneumoniae - Favorable (n=4, 2)
2
2
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=1, 2)
1
2
44. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the mMITT analysis set for blood only
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=32, 28)
31
28
Klebsiella pneumoniae - Favorable (n=4, 2)
3
2
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=1, 2)
1
2
45. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the mMITT analysis set for blood only
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
Escherichia coli - Favorable (n=32, 28)
29
27
Klebsiella pneumoniae - Favorable (n=4, 2)
3
2
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=1, 2)
1
2
46. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the Extended ME at EOT (IV) analysis set for blood only
Time Frame At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at EOT (IV) (EME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 336 371
Escherichia coli - Favorable (n=26, 24)
26
24
Klebsiella pneumoniae - Favorable (n=2, 1)
1
1
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=1, 2)
1
2
47. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the Extended ME at TOC analysis set for blood only
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (EME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
Escherichia coli - Favorable (n=22, 20)
22
20
Klebsiella pneumoniae - Favorable (n=2, 2)
2
2
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=0, 1)
0
1
48. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the Extended ME at LFU analysis set for blood only
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at LFU (EME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 251 272
Escherichia coli - Favorable (n=19, 18)
19
17
Klebsiella pneumoniae - Favorable (n=2, 1)
2
1
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=0, 1)
0
1
49. Secondary Outcome
Title Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the EOT (IV) visit in the ME at EOT (IV) analysis set for blood only
Time Frame At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at EOT (IV) (ME at EOT (IV))
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 325 361
Escherichia coli - Favorable (n=26, 24)
26
24
Klebsiella pneumoniae - Favorable (n=2, 1)
1
1
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=1, 2)
1
2
50. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the TOC visit in the ME at TOC analysis set for blood only
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
Escherichia coli - Favorable (n=22, 20)
22
20
Klebsiella pneumoniae - Favorable (n=2, 2)
2
2
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=0, 1)
0
1
51. Secondary Outcome
Title Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set)
Description Number of favorable per-pathogen microbiological responses at the LFU visit in the ME at LFU analysis set for blood only
Time Frame At LFU visit. LFU visit is 45 to 52 days from Randomization.

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at LFU (ME at LFU)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 245 262
Escherichia coli - Favorable (n=19, 18)
19
17
Klebsiella pneumoniae - Favorable (n=2, 1)
2
1
Proteus mirabilis - Favorable (n=1, 0)
1
0
Pseudomonas aeruginosa - Favorable (n=0, 1)
0
1
52. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set)
Description Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the mMITT analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
E. coli (MIC: <=0.008) - Favorable (n=5, 6)
3
5
E. coli (MIC: 0.015) - Favorable (n=8, 7)
8
6
E. coli (MIC: 0.03) - Favorable (n=28, 35)
24
23
E. coli (MIC: 0.06) - Favorable (n=123, 139)
103
111
E. coli (MIC: 0.12) - Favorable (n=90, 81)
67
54
E. coli (MIC: 0.25) - Favorable (n=28, 25)
18
13
E. coli (MIC: 0.5) - Favorable (n=5, 6)
4
2
E. coli (MIC: 1) - Favorable (n=3, 0)
1
0
E. coli (MIC: 2) - Favorable (n=1, 0)
1
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: 32) - Favorable (n=0, 0)
0
0
E. coli (MIC: >32) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
1
2
Kleb. pneumoniae (MIC: 0.06) - Favorable (n=9, 8)
7
8
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=11, 10)
9
7
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=4, 10)
1
3
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=8, 16)
6
11
Kleb. pneumoniae (MIC: 1) - Favorable (n=8, 5)
6
3
Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 4)
2
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 1)
0
1
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=1,1)
1
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=10, 5)
10
3
Proteus mirabilis (MIC: 0.06)- Favorable (n=6,6)
5
5
Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 0.5)- Favorable (n=0,1)
0
1
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
0
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 3,2)
2
2
Entero. cloacae (MIC: 0.25)- Favorable (n= 1,4)
0
1
Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
0
1
Entero. cloacae (MIC: 1)- Favorable (n= 2,5)
1
4
Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
1
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.5) - Favorable (n=0,2)
0
2
P.aeruginosa (MIC: 1) - Favorable (n=1,4)
1
2
P.aeruginosa (MIC: 2) - Favorable (n=5,5)
5
5
P.aeruginosa (MIC: 4) - Favorable (n=7,6)
3
4
P.aeruginosa (MIC: 8) - Favorable (n=2,2)
1
1
P.aeruginosa (MIC: 16) - Favorable (n=1,1)
0
1
P.aeruginosa (MIC: 32) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: >32) - Favorable (n=2,0)
2
0
53. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Description Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the Extended ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (EME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
E. coli (MIC: <=0.008) - Favorable (n=4,4)
2
4
E. coli (MIC: 0.015) - Favorable (n=5, 6)
5
5
E. coli (MIC: 0.03) - Favorable (n=18, 21)
17
17
E. coli (MIC: 0.06) - Favorable (n=95, 111)
83
94
E. coli (MIC: 0.12) - Favorable (n=68, 54)
56
40
E. coli (MIC: 0.25) - Favorable (n=19, 18)
13
8
E. coli (MIC: 0.5) - Favorable (n=2, 5)
2
2
E. coli (MIC: 1) - Favorable (n=2, 0)
1
0
E. coli (MIC: 2) - Favorable (n=1, 0)
1
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: 32) - Favorable (n=0, 0)
0
0
E. coli (MIC: >32) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
1
2
Kleb. pneumoniae (MIC: 0.06) - Favorable (n=5, 7)
4
7
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=8, 9)
7
6
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=3, 7)
1
2
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=6, 11)
4
8
Kleb. pneumoniae (MIC: 1) - Favorable (n=6, 4)
6
3
Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 1)
2
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 1)
0
1
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=1,0)
1
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=9, 2)
9
0
Proteus mirabilis (MIC: 0.06)- Favorable (n=4,5)
4
4
Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 0.5)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
0
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 1,2)
1
2
Entero. cloacae (MIC: 0.25)- Favorable (n= 0,3)
0
0
Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
0
1
Entero. cloacae (MIC: 1)- Favorable (n= 1,4)
1
4
Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
1
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.5) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 1) - Favorable (n=1,4)
1
2
P.aeruginosa (MIC: 2) - Favorable (n=4,5)
4
5
P.aeruginosa (MIC: 4) - Favorable (n=5,6)
1
4
P.aeruginosa (MIC: 8) - Favorable (n=2,2)
1
1
P.aeruginosa (MIC: 16) - Favorable (n=0,1)
0
1
P.aeruginosa (MIC: 32) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: >32) - Favorable (n=1,0)
1
0
54. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set)
Description Per pathogen microbiological response at TOC by CAZ-AVI MIC for baseline pathogen in the ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
E. coli (MIC: <=0.008) - Favorable (n=4,4)
2
4
E. coli (MIC: 0.015) - Favorable (n=5, 6)
5
5
E. coli (MIC: 0.03) - Favorable (n=18, 21)
17
17
E. coli (MIC: 0.06) - Favorable (n=95, 111)
83
94
E. coli (MIC: 0.12) - Favorable (n=68, 54)
56
40
E. coli (MIC: 0.25) - Favorable (n=19, 18)
13
8
E. coli (MIC: 0.5) - Favorable (n=2, 5)
2
2
E. coli (MIC: 1) - Favorable (n=2, 0)
1
0
E. coli (MIC: 2) - Favorable (n=1, 0)
1
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: 32) - Favorable (n=0, 0)
0
0
E. coli (MIC: >32) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 0.03) - Favorable (n=1, 2)
1
2
Kleb. pneumoniae (MIC: 0.06) - Favorable (n=5, 7)
4
7
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=8, 9)
7
6
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=3, 7)
1
2
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=6, 11)
4
8
Kleb. pneumoniae (MIC: 1) - Favorable (n=5, 4)
5
3
Kleb. pneumoniae (MIC: 2) - Favorable (n= 2, 1)
2
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 32) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: >32) - Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=1,0)
1
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=9, 2)
9
0
Proteus mirabilis (MIC: 0.06)- Favorable (n=4,5)
4
4
Proteus mirabilis (MIC: 0.12)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.25)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 0.5)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 32)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >32)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 0.06)- Favorable (n= 0, 1)
0
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 1,2)
1
2
Entero. cloacae (MIC: 0.25)- Favorable (n= 0,3)
0
0
Entero. cloacae (MIC: 0.5)- Favorable (n= 1,1)
0
1
Entero. cloacae (MIC: 1)- Favorable (n= 1,4)
1
4
Entero. cloacae (MIC: 2)- Favorable (n= 1,0)
1
0
Entero. cloacae (MIC: 4)- Favorable (n= 2,0)
1
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 32)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >32)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.12) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.25) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.5) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 1) - Favorable (n=1,4)
1
2
P.aeruginosa (MIC: 2) - Favorable (n=4,4)
4
4
P.aeruginosa (MIC: 4) - Favorable (n=3,4)
1
3
P.aeruginosa (MIC: 8) - Favorable (n=1,1)
1
0
P.aeruginosa (MIC: 16) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 32) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: >32) - Favorable (n=0,0)
0
0
55. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set)
Description Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the mMITT analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological modified intent to treat analysis set (mMITT)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 393 417
E. coli (MIC: <=0.008) - Favorable (n=1, 3)
1
3
E. coli (MIC: 0.015) - Favorable (n=160, 160)
127
119
E. coli (MIC: 0.03) - Favorable (n=112, 123)
89
86
E. coli (MIC: 0.06) - Favorable (n=14, 10)
10
4
E. coli (MIC: 0.12) - Favorable (n=3, 3)
1
2
E. coli (MIC: 0.25) - Favorable (n=1, 0)
1
0
E. coli (MIC: 0.5) - Favorable (n=0,0)
0
0
E. coli (MIC: 1) - Favorable (n=0, 0)
0
0
E. coli (MIC: 2) - Favorable (n=0, 0)
0
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: >16) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 3)
1
2
Kleb. pneumoniae (MIC: 0.03)-Favorable (n=22, 27)
16
21
Kleb. pneumoniae (MIC: 0.06)- Favorable (n=11, 16)
10
7
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=4,4)
2
2
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2,3)
1
2
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=2, 1)
1
0
Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 2) - Favorable (n= 0, 0)
0
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 1)
0
1
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 1)
0
0
Kleb. pneumoniae (MIC: >16) - Favorable (n=1, 0)
1
0
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=1, 0)
1
0
Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
2
1
Proteus mirabilis (MIC: 0.12)- Favorable (n=6,5)
5
4
Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 4)
6
2
Proteus mirabilis (MIC: 0.5)- Favorable (n=2,2)
2
2
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 3,1)
2
1
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,5)
1
2
Entero. cloacae (MIC: 0.06)- Favorable (n= 3, 1)
1
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 0, 4)
0
4
Entero. cloacae (MIC: 0.25)- Favorable (n= 0,1)
0
0
Entero. cloacae (MIC: 0.5)- Favorable (n= 4,0)
2
0
Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
0
1
Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
2
3
P.aeruginosa (MIC: 0.12) - Favorable (n=2,2)
1
2
P.aeruginosa (MIC: 0.25) - Favorable (n=2,5)
2
2
P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
2
1
P.aeruginosa (MIC: 1) - Favorable (n=1,4)
0
3
P.aeruginosa (MIC: 2) - Favorable (n=1,0)
1
0
P.aeruginosa (MIC: 4) - Favorable (n=2,2)
1
1
P.aeruginosa (MIC: 8) - Favorable (n=2,1)
1
1
P.aeruginosa (MIC: 16) - Favorable (n=2,1)
0
1
P.aeruginosa (MIC: >16) - Favorable (n=2,1)
2
1
56. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)
Description Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the Extended ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Extended microbiological evaluable analysis set at TOC (EME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 292 311
E. coli (MIC: <=0.008) - Favorable (n=1,1)
1
1
E. coli (MIC: 0.015) - Favorable (n=122, 119)
106
95
E. coli (MIC: 0.03) - Favorable (n=79, 89)
64
70
E. coli (MIC: 0.06) - Favorable (n=10, 8)
7
3
E. coli (MIC: 0.12) - Favorable (n=1, 2)
1
1
E. coli (MIC: 0.25) - Favorable (n=1, 0)
1
0
E. coli (MIC: 0.5) - Favorable (n=0, 0)
0
0
E. coli (MIC: 1) - Favorable (n=0, 0)
0
0
E. coli (MIC: 2) - Favorable (n=0, 0)
0
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: >16) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 2)
1
1
Kleb. pneumoniae (MIC:0.03) - Favorable (n=15, 23)
12
18
Kleb. pneumoniae (MIC: 0.06) - Favorable (n=8, 12)
7
6
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=3, 2)
2
2
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2, 2)
1
1
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 2) - Favorable (n= 0,0)
0
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 1)
0
1
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: >16) - Favorable (n=1, 0)
1
0
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=1,0)
1
0
Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
2
1
Proteus mirabilis (MIC: 0.12)- Favorable (n=4,2)
4
2
Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 3)
6
1
Proteus mirabilis (MIC: 0.5)- Favorable (n=1,0)
1
0
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 1,1)
1
1
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,4)
1
1
Entero. cloacae (MIC: 0.06)- Favorable (n= 2, 1)
1
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 0,4)
0
4
Entero. cloacae (MIC: 0.25)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.5)- Favorable (n= 3,0)
2
0
Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
0
1
Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
2
3
P.aeruginosa (MIC: 0.12) - Favorable (n=1,2)
0
2
P.aeruginosa (MIC: 0.25) - Favorable (n=2,4)
2
1
P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
2
1
P.aeruginosa (MIC: 1) - Favorable (n=1,3)
0
2
P.aeruginosa (MIC: 2) - Favorable (n=1,0)
1
0
P.aeruginosa (MIC: 4) - Favorable (n=0,2)
0
1
P.aeruginosa (MIC: 8) - Favorable (n=1,1)
0
1
P.aeruginosa (MIC: 16) - Favorable (n=2,1)
0
1
P.aeruginosa (MIC: >16) - Favorable (n=1,1)
1
1
57. Secondary Outcome
Title Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set)
Description Per pathogen microbiological response at TOC by Doripenem MIC for baseline pathogen in the ME at TOC analysis set
Time Frame At TOC visit. TOC visit is 21 to 25 days from Randomization

Outcome Measure Data

Analysis Population Description
Microbiological evaluable analysis set at TOC (ME at TOC)
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
Measure Participants 286 298
E. coli (MIC: <=0.008) - Favorable (n=1,1)
1
1
E. coli (MIC: 0.015) - Favorable (n=122, 119)
106
95
E. coli (MIC: 0.03) - Favorable (n=79, 89)
64
70
E. coli (MIC: 0.06) - Favorable (n=10, 8)
7
3
E. coli (MIC: 0.12) - Favorable (n=1,2)
1
1
E. coli (MIC: 0.25) - Favorable (n=1,0)
1
0
E. coli (MIC: 0.5) - Favorable (n=0,0)
0
0
E. coli (MIC: 1) - Favorable (n=0, 0)
0
0
E. coli (MIC: 2) - Favorable (n=0, 0)
0
0
E. coli (MIC: 4) - Favorable (n=0, 0)
0
0
E. coli (MIC: 8) - Favorable (n=0, 0)
0
0
E. coli (MIC: 16) - Favorable (n=0, 0)
0
0
E. coli (MIC: >16) - Favorable (n=0, 0)
0
0
Kleb.pneumoniae (MIC: <=0.008)-Favorable(n=0, 0)
0
0
Kleb. pneumoniae (MIC: 0.015) - Favorable (n=1, 2)
1
1
Kleb. pneumoniae (MIC:0.03) - Favorable (n=15, 23)
12
18
Kleb. pneumoniae (MIC: 0.06) - Favorable (n=8, 12)
7
6
Kleb.pneumoniae (MIC: 0.12) -Favorable(n=3,2)
2
2
Kleb. pneumoniae (MIC: 0.25) - Favorable (n=2, 2)
1
1
Kleb. pneumoniae (MIC: 0.5) - Favorable (n=1,0)
1
0
Kleb. pneumoniae (MIC: 1) - Favorable (n=1, 0)
1
0
Kleb. pneumoniae (MIC: 2) - Favorable (n= 0,0)
0
0
Kleb. pneumoniae (MIC: 4) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 8) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: 16) - Favorable (n=0, 0)
0
0
Kleb. pneumoniae (MIC: >16) - Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC:<=0.008)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.015)- Favorable (n=0,0)
0
0
Proteus mirabilis (MIC: 0.03)- Favorable (n=1, 0)
1
0
Proteus mirabilis (MIC: 0.06)- Favorable (n=2,2)
2
1
Proteus mirabilis (MIC: 0.12)- Favorable (n=4,2)
4
2
Proteus mirabilis (MIC: 0.25)- Favorable (n=6, 3)
6
1
Proteus mirabilis (MIC: 0.5)- Favorable (n=1,0)
1
0
Proteus mirabilis (MIC: 1)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 2)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 4)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 8)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: 16)- Favorable (n=0, 0)
0
0
Proteus mirabilis (MIC: >16)- Favorable (n=0, 0)
0
0
Entero. cloacae (MIC: <=0.008)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.015)- Favorable (n= 1,1)
1
1
Entero. cloacae (MIC: 0.03)- Favorable (n= 1,4)
1
1
Entero. cloacae (MIC: 0.06)- Favorable (n= 2, 1)
1
1
Entero. cloacae (MIC: 0.12)- Favorable (n= 0,4)
0
4
Entero. cloacae (MIC: 0.25)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 0.5)- Favorable (n= 3,0)
2
0
Entero. cloacae (MIC: 1)- Favorable (n= 0,1)
0
1
Entero. cloacae (MIC: 2)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 4)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 8)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: 16)- Favorable (n= 0,0)
0
0
Entero. cloacae (MIC: >16)- Favorable (n= 0,0)
0
0
P.aeruginosa (MIC: <=0.008) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.015) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.03) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 0.06) - Favorable (n=2,3)
2
3
P.aeruginosa (MIC: 0.12) - Favorable (n=1,2)
0
2
P.aeruginosa (MIC: 0.25) - Favorable (n=2,4)
2
1
P.aeruginosa (MIC: 0.5) - Favorable (n=2,1)
2
1
P.aeruginosa (MIC: 1) - Favorable (n=1,3)
0
2
P.aeruginosa (MIC: 2) - Favorable (n=1,0)
1
0
P.aeruginosa (MIC: 4) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 8) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: 16) - Favorable (n=0,0)
0
0
P.aeruginosa (MIC: >16) - Favorable (n=0,0)
0
0
58. Secondary Outcome
Title Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame within 15 minutes before/after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (ceftazidime within 15 minutes before/after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 480
Geometric Mean (Full Range) [NG/ML]
65481.2
59. Secondary Outcome
Title Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame Between 30 to 90 minutes after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (ceftazidime between 30 to 90 minutes after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 483
Geometric Mean (Full Range) [NG/ML]
47575.1
60. Secondary Outcome
Title Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame Between 300 to 360 minutes after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (ceftazidime between 300 to 360 minutes after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 481
Geometric Mean (Full Range) [NG/ML]
16959.6
61. Secondary Outcome
Title Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame within 15 minutes before/after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (avibactam within 15 minutes before/after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 489
Geometric Mean (Full Range) [NG/ML]
9307.3
62. Secondary Outcome
Title Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame Between 30 to 90 minutes after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (avibactam between 30 to 90 minutes after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 490
Geometric Mean (Full Range) [NG/ML]
6587.2
63. Secondary Outcome
Title Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set)
Description Blood samples were taken on Day 3 for ceftazidime (CAZ) and avibactam (AVI) plasma concentration.
Time Frame Between 300 to 360 minutes after dose

Outcome Measure Data

Analysis Population Description
PK analysis set (avibactam between 300 to 360 minutes after dose)
Arm/Group Title CAZ-AVI
Arm/Group Description Ceftazidime-avibactam treatment group
Measure Participants 488
Geometric Mean (Full Range) [NG/ML]
1883.2

Adverse Events

Time Frame
Adverse Event Reporting Description The summaries for adverse events are based on the safety analysis set. There is a total of 1020 patients in safety analysis set in both protocol D4280C00002 (i.e. 517 patients) and protocol D4280C00004 (i.e. 503 patients). A total of 13 patients (out of the1033 randomized patients) did not receive any amount of IV study therapy.
Arm/Group Title CAZ-AVI Doripenem
Arm/Group Description Ceftazidime-avibactam treatment group Doripenem treatment group
All Cause Mortality
CAZ-AVI Doripenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
CAZ-AVI Doripenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 21/511 (4.1%) 12/509 (2.4%)
Cardiac disorders
Angina pectoris 2/511 (0.4%) 2 0/509 (0%) 0
Angina unstable 1/511 (0.2%) 1 1/509 (0.2%) 1
Atrial fibrillation 0/511 (0%) 0 1/509 (0.2%) 1
Coronary artery aneurysm 1/511 (0.2%) 1 0/509 (0%) 0
Gastrointestinal disorders
Abdominal pain 0/511 (0%) 0 1/509 (0.2%) 1
Diarrhoea 1/511 (0.2%) 1 0/509 (0%) 0
Enterovesical fistula 1/511 (0.2%) 1 0/509 (0%) 0
Retroperitoneal haematoma 1/511 (0.2%) 1 0/509 (0%) 0
Infections and infestations
Abdominal abscess 1/511 (0.2%) 1 0/509 (0%) 0
Appendicitis 0/511 (0%) 0 1/509 (0.2%) 1
Cellulitis 1/511 (0.2%) 1 0/509 (0%) 0
Chronic hepatitis C 1/511 (0.2%) 1 0/509 (0%) 0
Clostridium difficile colitis 1/511 (0.2%) 1 0/509 (0%) 0
Diverticulitis 1/511 (0.2%) 1 0/509 (0%) 0
Gastroenteritis 1/511 (0.2%) 1 0/509 (0%) 0
Orchitis 0/511 (0%) 0 1/509 (0.2%) 1
Pneumonia 0/511 (0%) 0 1/509 (0.2%) 1
Urinary tract infection 0/511 (0%) 0 1/509 (0.2%) 1
Injury, poisoning and procedural complications
Post procedural haemorrhage 0/511 (0%) 0 1/509 (0.2%) 1
Procedural haemorrhage 1/511 (0.2%) 1 0/509 (0%) 0
Radius fracture 0/511 (0%) 0 1/509 (0.2%) 1
Musculoskeletal and connective tissue disorders
Spinal pain 1/511 (0.2%) 1 0/509 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer 1/511 (0.2%) 1 0/509 (0%) 0
Prostate cancer 0/511 (0%) 0 1/509 (0.2%) 1
Nervous system disorders
Hypoglycaemic seizure 0/511 (0%) 0 1/509 (0.2%) 1
Tension headache 0/511 (0%) 0 1/509 (0.2%) 1
Renal and urinary disorders
Calculus ureteric 1/511 (0.2%) 1 0/509 (0%) 0
Hydronephrosis 1/511 (0.2%) 1 0/509 (0%) 0
Nephrolithiasis 3/511 (0.6%) 4 0/509 (0%) 0
Renal failure chronic 0/511 (0%) 0 1/509 (0.2%) 1
Renal impairment 1/511 (0.2%) 1 0/509 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 0/511 (0%) 0 1/509 (0.2%) 1
Hyperventilation 1/511 (0.2%) 1 0/509 (0%) 0
Vascular disorders
Thrombophlebitis superficial 1/511 (0.2%) 1 0/509 (0%) 0
Other (Not Including Serious) Adverse Events
CAZ-AVI Doripenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 67/511 (13.1%) 57/509 (11.2%)
Gastrointestinal disorders
Constipation 11/511 (2.2%) 11 7/509 (1.4%) 8
Diarrhoea 13/511 (2.5%) 14 6/509 (1.2%) 6
Nausea 15/511 (2.9%) 16 10/509 (2%) 10
Nervous system disorders
Headache 38/511 (7.4%) 41 40/509 (7.9%) 41

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal investigator submits the proposed publication and /or presentation to AZAB for review at least 60 days prior to proposed publication and/or presentation. If AZAB, requests in writing, then PI shall withhold publication and/or presentation for an additional 90 days to allow AZAB to protect its intellectual rights.

Results Point of Contact

Name/Title Gayan Makumburage
Organization AstraZeneca/ PPD
Phone 9105588682
Email gayan.makumburage@ppdi.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01595438
Other Study ID Numbers:
  • D4280C00002
  • 2011-005721-43
First Posted:
May 10, 2012
Last Update Posted:
Sep 6, 2017
Last Verified:
Aug 1, 2017