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Evaluation of Safety, Pharmacokinetics and Efficacy of Ceftazidime and Avibactam (CAZ-AVI ) Compared With Cefepime in Children From 3 Months to Less Than 18 Years of Age With Complicated Urinary Tract Infections (cUTIs)

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ClinicalTrials.gov Identifier: NCT02497781
Recruitment Status : Completed
First Posted : July 15, 2015
Results First Posted : April 10, 2018
Last Update Posted : July 11, 2018
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Complicated Urinary Tract Infections
Interventions Drug: Ceftazidime -avibactam
Drug: Cefepime
Enrollment 97
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion. Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Period Title: Overall Study
Started 68 29
Treated 67 28
Completed 64 26
Not Completed 4 3
Reason Not Completed
Withdrawal by Subject             2             0
Lack of Efficacy             0             1
Randomised but not treated             1             1
Lost to Follow-up             1             1
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime Total
Hide Arm/Group Description Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion. Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion. Total of all reporting groups
Overall Number of Baseline Participants 67 28 95
Hide Baseline Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 28 participants 95 participants
6.08  (5.647) 6.19  (6.072) 6.12  (5.743)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 28 participants 95 participants
Female
56
  83.6%
21
  75.0%
77
  81.1%
Male
11
  16.4%
7
  25.0%
18
  18.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 28 participants 95 participants
Hispanic or Latino
1
   1.5%
0
   0.0%
1
   1.1%
Not Hispanic or Latino
66
  98.5%
28
 100.0%
94
  98.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 28 participants 95 participants
American Indian or Alaska Native
1
   1.5%
0
   0.0%
1
   1.1%
Asian
12
  17.9%
5
  17.9%
17
  17.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
49
  73.1%
23
  82.1%
72
  75.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   7.5%
0
   0.0%
5
   5.3%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 67 participants 28 participants 95 participants
108.7  (34.40) 108.9  (37.16) 108.7  (35.03)
1.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to late follow-up (LFU) visit (20 to 36 days after last dose of study treatment [IV or oral]) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE.
Time Frame Baseline until the LFU visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
AEs 53.7 53.6
SAEs 11.9 7.1
2.Primary Outcome
Title Percentage of Participants With Cephalosporin Class Effects and Additional Adverse Events (AEs)
Hide Description Percentage of participants with Cephalosporin class effects (defined as adverse event of special interest (AEoSI) within the safety topics (ST) of hypersensitivity/anaphylaxis) and additional AEs (which included AEs of diarrhea, renal disorder, hematological disorder and liver disorder relevant to the cephalosporin class within the safety topics (ST) based on MedDRA 20.0) were reported in this outcome measure.
Time Frame Baseline until the LFU visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
AE in the ST of Diarrhea 7.5 10.7
AE in the ST of Hematological Disorders 0 0
AEoSI in the ST of Hypersensitivity/Anaphylaxis 7.5 7.1
AE in the ST of Liver Disorder 1.5 0
AE in the ST of Renal Disorder 0 0
3.Primary Outcome
Title Change From Baseline in Pulse Rate at End of Intravenous Treatment (EOIV) Visit
Hide Description EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline, EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Mean (Standard Deviation)
Unit of Measure: beats per minute
Baseline 111.5  (23.97) 119.1  (27.08)
Change at EOIV -11.9  (18.65) -17.1  (24.58)
4.Primary Outcome
Title Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End of Intravenous Treatment (EOIV) Visit
Hide Description EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline, EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
SBP: Baseline 105.6  (14.88) 111.9  (14.61)
SBP: Change at EOIV -1.0  (15.11) -5.4  (14.53)
DBP: Baseline 62.6  (12.68) 69.1  (9.28)
DBP: Change at EOIV 0.9  (15.41) -5.0  (7.50)
5.Primary Outcome
Title Change From Baseline in Respiratory Rate at End of Intravenous Treatment (EOIV) Visit
Hide Description EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline, EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Mean (Standard Deviation)
Unit of Measure: breaths per minute
Baseline Number Analyzed 67 participants 28 participants
25.8  (5.96) 27.0  (8.46)
Change at EOIV Number Analyzed 67 participants 27 participants
-2.5  (4.64) -2.6  (7.96)
6.Primary Outcome
Title Change From Baseline in Body Temperature at End of Intravenous Treatment (EOIV) Visit
Hide Description EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline, EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime). Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 66 28
Mean (Standard Deviation)
Unit of Measure: degree Celsius
Baseline 37.67  (1.043) 37.49  (1.031)
Change at EOIV -1.15  (1.096) -0.90  (1.036)
7.Primary Outcome
Title Percentage of Participants With Abnormal Physical Examination Findings at End of Intravenous Treatment (EOIV) Visit
Hide Description Physical examination included an assessment of the following: general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, respiratory system, cardiovascular system, abdomen, musculoskeletal system (including spine and extremities), and neurological system. Participants with new or aggravated abnormal physical examination findings with regard to baseline findings were reported. Abnormality in physical examinations were based on blinded observer's discretion. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
Abdomen 0 3.6
Cardiovascular System 1.5 0
General Appearance 0 0
Head and Neck 1.5 3.6
Lymph Nodes 0 3.6
Musculoskeletal System 0 0
Neurological System 0 0
Respiratory System 3.0 0
Skin 3.0 7.1
Thyroid 0 0
8.Primary Outcome
Title Change From Baseline in Body Weight at End of Intravenous Treatment (EOIV) Visit
Hide Description EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline, EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Mean (Standard Deviation)
Unit of Measure: kilogram
Baseline Number Analyzed 67 participants 28 participants
24.55  (19.361) 25.24  (21.527)
Change at EOIV Number Analyzed 66 participants 28 participants
-0.08  (0.613) 0.14  (0.510)
9.Primary Outcome
Title Percentage of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters
Hide Description Criteria for potentially clinically significant laboratory abnormalities: hematology (platelets: <0.4*lower limit of normal [LLN], >2*upper limit of normal [ULN], >40% decrease from baseline [DFB],>100% Increase from baseline [IFB]; Chemistry (Bicarbonate: <0.7*LLN, >1.3*ULN, >50% DFB, >30% IFB).
Time Frame Baseline until the LFU visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime). Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 62 26
Measure Type: Number
Unit of Measure: percentage of participants
Chemistry: Bicarbonate Number Analyzed 51 participants 23 participants
2.0 0
Hematology: Platelets Number Analyzed 62 participants 26 participants
1.6 0
10.Primary Outcome
Title Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
Hide Description PCS criteria for abnormal value of ECG parameters: QT interval >=450 milliseconds (msec); 480 msec; >=500 msec; Increase from baseline (IFB) of >=30 msec; >=60 msec and >90 msec; Decrease from baseline (DFB) of >=30 msec; >=60 msec and >90 msec. QT interval using Bazett's correction (QTcB): >=450 milliseconds (msec); 480 msec; >=500 msec; Increase from baseline (IFB) of >=30 msec; >=60 msec and >90 msec; DFB of >=30 msec; >=60 msec and >90 msec. QT interval using Fridericia's correction (QTcF): >=450 msec; 480 msec; >=500 msec; IFB of >=30 msec; >=60 msec and >90 msec; DFB of >=30 msec; >=60 msec and >90 msec. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame Baseline until the EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
QT Interval : >450 msec 0 0
QT Interval : >480 msec 0 0
QT Interval : >500 msec 0 0
Maximum IFB QT Interval : > 30 msec 19.4 14.3
Maximum IFB QT Interval : > 60 msec 7.5 3.6
Maximum IFB QT Interval : >90 msec 3.0 0
Maximum DFB QT Interval : > 30 msec 9.0 17.9
Maximum DFB QT Interval : > 60 msec 4.5 0
Maximum DFB QT Interval : > 90 msec 1.5 0
QTcB Interval : >450 msec 16.4 3.6
QTcB Interval : >480 msec 11.9 0
QTcB Interval : >500 msec 7.5 0
Maximum IFB QTcB Interval : > 30 msec 17.9 14.3
Maximum IFB QTcB Interval : > 60 msec 7.5 3.6
Maximum IFB QTcB Interval : > 90 msec 3.0 0
Maximum DFB QTcB Interval : > 30 msec 10.4 7.1
Maximum DFB QTcB Interval : > 60 msec 6.0 3.6
Maximum DFB QTcB Interval : > 90 msec 1.5 3.6
QTcF Interval : >450 msec 6.0 0
QTcF Interval : >480 msec 6.0 0
QTcF Interval : >500 msec 6.0 0
Maximum IFB QTcF Interval : > 30 msec 17.9 14.3
Maximum IFB QTcF Interval : > 60 msec 3.0 3.6
Maximum IFB QTcF Interval : > 90 msec 3.0 0
Maximum DFB QTcF Interval : > 30 msec 9.0 10.7
Maximum DFB QTcF Interval : > 60 msec 3.0 3.6
Maximum DFB QTcF Interval : > 90 msec 1.5 0
11.Primary Outcome
Title Percentage of Participants With Creatinine Clearance (CrCl) at Day 7
Hide Description CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
CrCl: <30mL/min/1.73 m^2 0 0
CrCl: >=30 to <50mL/min/1.73 m^2 0 0
CrCl: >=50 to <80mL/min/1.73 m^2 11.1 0
CrCl: >=80mL/min/1.73 m^2 88.9 100
12.Primary Outcome
Title Percentage of Participants With Creatinine Clearance (CrCl) at End of Intravenous Treatment (EOIV) Visit
Hide Description CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
CrCl: <30mL/min/1.73 m^2 0 0
CrCl: >=30 to <50mL/min/1.73 m^2 0 0
CrCl: >=50 to <80mL/min/1.73 m^2 20.0 13.6
CrCl: >=80mL/min/1.73 m^2 80.0 86.4
13.Primary Outcome
Title Percentage of Participants With Creatinine Clearance (CrCl) at Test of Cure (TOC) Visit
Hide Description CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: <30 mL/min/1.73 m^2, >=30 to <50 mL/min/1.73 m^2, >=50 mL/min/1.73 m^2 to <80 mL/min/1.73 m^2, and >=80 mL/min/1.73 m^2. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral).
Time Frame TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 67 28
Measure Type: Number
Unit of Measure: percentage of participants
CrCl: <30mL/min/1.73 m^2 0 0
CrCl: >=30 to <50mL/min/1.73 m^2 0 0
CrCl: >=50 to <80mL/min/1.73 m^2 25.0 41.7
CrCl: >=80mL/min/1.73 m^2 75.0 58.3
14.Secondary Outcome
Title Plasma Concentrations of Ceftazidime and Avibactam
Hide Description [Not Specified]
Time Frame 15, 30-90, 300-360 minutes post-dose on Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set included all randomized participants who received any amount of CAZ-AVI and had at least 1 CAZ and/ or AVI plasma measurement available. This outcome measure was not planned to be analyzed for Cefepime receiving cohort, as pre-specified in protocol.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI)
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 64
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Ceftazidime: 15 minute post-dose on Day 3 Number Analyzed 62 participants
61411.2  (39276.40)
Ceftazidime: 30-90 minute post-dose on Day 3 Number Analyzed 59 participants
47638.5  (31948.31)
Ceftazidime:300-360minute post-dose on Day 3 Number Analyzed 62 participants
7285.7  (11396.88)
Avibactam: 15 minute post-dose on Day 3 Number Analyzed 62 participants
9577.4  (6922.76)
Avibactam: 30-90 minute post-dose on Day 3 Number Analyzed 59 participants
7046.4  (6060.75)
Avibactam: 300-360 minute post-dose on Day 3 Number Analyzed 62 participants
936.3  (1499.00)
15.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR): Intent-to-treat (ITT) Analysis Population
Hide Description Favorable CR was defined as a CR of improvement and cure(at end of 72 hours(hr) and EOIV) and a CR of cure(at EOT and TOC).Cure is resolution of all acute signs/symptoms of cUTI/improvement to such an extent that no further antimicrobial therapy required.Improvement is:1)at end of 72hr study drug treatment: improvement but not enough to switch to oral therapy and still on IV study drug at end of 72hr and meet following criterion: Absence of new signs/symptoms, and improvement in at least 1 symptom/sign(ie, fever,pain,tenderness,elevated WBCs,elevated CRP) from Baseline,and with no worsening of any symptom/sign. 2) at EOIV: participants who switched to oral therapy and had afebrile(temperature<=38.0°C) for >=24hr;absence of new and improvement in at least 1 symptom/sign from Baseline and worsening of none.EOT visit occurred within 48hr after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study(if on oral switch therapy).
Time Frame End of 72 hours study drug treatment, EOIV visit (anytime from Day 4 to 15), EOT visit (up to Day 16), TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis population included all participants who had been assigned a randomized treatment.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 68 29
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
End of 72 hours
88.2
(79.0 to 94.3)
86.2
(70.5 to 95.2)
EOIV
91.2
(82.7 to 96.2)
89.7
(74.9 to 97.0)
EOT
88.2
(79.0 to 94.3)
89.7
(74.9 to 97.0)
TOC
86.8
(77.2 to 93.2)
82.8
(66.3 to 93.1)
16.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR): Microbiological ITT (Micro-ITT) Analysis Population
Hide Description Favorable CR was defined as a CR of improvement and cure(at end of 72 hours(hr) and EOIV) and a CR of cure(at EOT and TOC).Cure is resolution of all acute signs/symptoms of cUTI/improvement to such an extent that no further antimicrobial therapy required.Improvement is:1)at end of 72hr study drug treatment: improvement but not enough to switch to oral therapy and still on IV study drug at end of 72hr and meet following criterion: Absence of new signs/symptoms, and improvement in at least 1 symptom/sign(ie, fever,pain,tenderness,elevated WBCs,elevated CRP) from Baseline,and with no worsening of any symptom/sign. 2) at EOIV: participants who switched to oral therapy and had afebrile(temperature<=38.0°C) for >=24hr;absence of new and improvement in at least 1 symptom/sign from Baseline and worsening of none.EOT visit occurred within 48hr after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study(if on oral switch therapy).
Time Frame End of 72 hours study drug treatment, EOIV visit (anytime from Day 4 to 15), EOT visit (up to Day 16), TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Micro-ITT analysis population included all randomized participants who had at least 1 gram negative typical pathogen (in the urine) at baseline known to cause cUTI and no gram positive pathogen (in the urine) at baseline.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 54 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
End of 72 hours
90.7
(80.9 to 96.4)
95.7
(81.4 to 99.5)
EOIV
96.3
(88.6 to 99.2)
95.7
(81.4 to 99.5)
EOT
90.7
(80.9 to 96.4)
95.7
(81.4 to 99.5)
TOC
88.9
(78.5 to 95.2)
82.6
(63.8 to 93.8)
17.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR) at End of 72 Hours Treatment: Clinically Evaluable (CE) Analysis Set at 72 Hours
Hide Description Favourable clinical response was defined as a CR of improvement and cure. Cure was defined as resolution of all acute signs and symptoms of complicated urinary tract infections (cUTIs) or improvement to such an extent that no further antimicrobial therapy was required. Clinical Improvement included all the participants who had improvement but not enough to switch to oral therapy and were still on IV study drug at End of 72 hours and had meet the following criterion: absence of new signs and symptoms, and improvement in at least 1 symptom or sign (fever, pain, tenderness, elevated WBCs, elevated CRP) from baseline, and with no worsening of any symptom or sign.
Time Frame End of 72 hours study drug treatment on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
CE analysis set at 72hr: participants who had at least 1 gram negative typical pathogen (in urine) at baseline known to cause cUTI, no gram positive pathogen (in urine) at baseline, confirmed diagnosis of cUTI, >=48hr of IV study drug, unless discontinued due to treatment-limiting AE, no important protocol deviations and no concomitant antibiotics.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 47 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100
(94.8 to 100)
95.2
(79.8 to 99.5)
18.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR) at End of Intravenous Treatment (EOIV) Visit: Clinically Evaluable (CE) Analysis Set at EOIV
Hide Description Favourable clinical response was defined as a CR of improvement and cure. Cure was defined as resolution of all acute signs and symptoms of complicated urinary tract infections (cUTIs) or improvement to such an extent that no further antimicrobial therapy was required. Clinical Improvement included all the participants who had switched to oral therapy and had meet the following criterion: afebrile (temperature <=38.0°C) for at least 24 hours, absence of new and improvement in at least 1 symptom or sign (fever, pain, tenderness, elevated WBCs, elevated c-reactive-protein) from baseline and worsening of none. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Time Frame EOIV visit (anytime from Day 4 to 15)
Hide Outcome Measure Data
Hide Analysis Population Description
CE analysis set at EOIV: participants >=1 gram negative typical pathogen known to cause cUTI, no gram positive pathogen (in urine) at baseline, confirmed cUTI diagnosis, >=48 h of IV study drug, unless discontinued due to AE, no important protocol deviations, no concomitant antibiotic, had clinical response of cure, improvement or failure at EOIV.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 52 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
98.1
(91.4 to 99.8)
95.5
(80.7 to 99.5)
19.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR) at End of Treatment (EOT) Visit: Clinically Evaluable (CE) Analysis Set at EOT
Hide Description Favourable clinical response was defined as a CR cure. Cure was defined as resolution of all acute signs and symptoms of complicated urinary tract infections (cUTIs) or improvement to such an extent that no further antimicrobial therapy was required. EOT visit occurred within 48hr after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study(if on oral switch therapy).
Time Frame EOT visit (up to Day 16)
Hide Outcome Measure Data
Hide Analysis Population Description
CE analysis set at EOT: participants >=1 gram negative typical pathogen known to cause cUTI, no gram positive pathogen (in urine) at baseline, confirmed cUTI diagnosis, >=48hr of IV study drug, unless discontinued due to AE, no important protocol deviations, no concomitant antibiotic, had clinical response of cure, improvement or failure at EOT.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 49 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
98.0
(90.9 to 99.8)
94.7
(77.9 to 99.4)
20.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR) at TOC: Clinically Evaluable (CE) Analysis Set at TOC
Hide Description Favourable clinical response was defined as resolution of all acute signs/symptoms of cUTIs or improvement to such an extent that no further antimicrobial therapy was needed. Participants who met the following criterion: Incomplete resolution or worsening of cUTI signs or symptoms or development of new signs or symptoms requiring alternative non-study antimicrobial therapy or death in which cUTI was contributory. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral).
Time Frame TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
CE analysis set at TOC: participants >=1 gram negative typical pathogen known to cause cUTI, no gram positive pathogen (in urine) at baseline, confirmed cUTI diagnosis, >=48hr of IV study drug, unless discontinued due to AE, no important protocol deviations, no concomitant antibiotic, had clinical response of cure, improvement or failure at TOC.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 49 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
93.9
(84.6 to 98.2)
85.0
(65.1 to 95.6)
21.Secondary Outcome
Title Percentage of Participants With Favourable Clinical Response (CR): Microbiologically Evaluable (ME) Analysis Population
Hide Description Favorable CR was defined as a CR of improvement and cure(at end of 72 hours(hr) and EOIV) and a CR of cure(at EOT and TOC).Cure is resolution of all acute signs/symptoms of cUTI/improvement to such an extent that no further antimicrobial therapy required.Improvement is:1)at end of 72hr study drug treatment: improvement but not enough to switch to oral therapy and still on IV study drug at end of 72hr and meet following criterion: Absence of new signs/symptoms, and improvement in at least 1 symptom/sign(ie, fever,pain,tenderness,elevated WBCs,elevated CRP) from Baseline,and with no worsening of any symptom/sign. 2) at EOIV: participants who switched to oral therapy and had afebrile(temperature<=38.0°C) for >=24hr;absence of new and improvement in at least 1 symptom/sign from Baseline and worsening of none.EOT visit occurred within 48hr after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study(if on oral switch therapy).
Time Frame EOIV visit (anytime from Day 4 to 15), EOT visit (up to Day 16), TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set: participants >=1gram(-ve) and no gram(+ve) pathogen (in urine) at baseline, confirmed cUTI diagnosis, had >=48hr IV study drug, unless discontinued due to AE, no important protocol deviation, concomitant antibiotic, >=1gram(-ve) typical UTI bacterial pathogen at Baseline susceptible to study drug and MR which was not indeterminate.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 41 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
EOIV Number Analyzed 35 participants 16 participants
100
(93.1 to 100)
100
(85.7 to 100)
EOT Number Analyzed 39 participants 14 participants
100
(93.8 to 100)
100
(83.8 to 100)
TOC Number Analyzed 41 participants 16 participants
92.7
(81.7 to 97.9)
87.5
(65.6 to 97.3)
22.Secondary Outcome
Title Percentage of Participants With Favourable Microbiological Response: Microbiological Intent-to-treat (Micro-ITT) Population
Hide Description Favourable microbiological response was achieved when all baseline pathogens were eradicated. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. EOT visit occurred within 48 hours after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study if on oral switch therapy (which occurred within the maximum study treatment duration of 14 days).
Time Frame EOIV visit (Day 4 to 15), EOT visit(up to Day 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Micro-ITT analysis population included all randomized participants who had at least 1 gram negative typical pathogen (in the urine) at baseline known to cause cUTI and no gram cUTI and no gram positive pathogen (in the urine) at baseline.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 54 23
Measure Type: Number
Unit of Measure: percentage of participants
EOIV 81.5 78.3
EOT 83.3 73.9
23.Secondary Outcome
Title Percentage of Participants With Favourable Microbiological Response: Microbiologically Evaluable (ME) Analysis Population
Hide Description Favourable microbiological response was achieved when all baseline pathogens were eradicated. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. EOT visit occurred within 48 hours after completion of the last dose of oral switch therapy or at time of premature discontinuation/early withdrawal from study if on oral switch therapy (which occurred within the maximum study treatment duration of 14 days).
Time Frame EOIV visit (Day 4 to 15), EOT visit (up to Day 16)
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set: participants >=1gram(-ve) and no gram(+ve) pathogen (in urine) at baseline, confirmed cUTI diagnosis, had >=48hr IV study drug, unless discontinued due to AE, no important protocol deviation, concomitant antibiotic, >=1gram(-ve) typical UTI bacterial pathogen at Baseline susceptible to study drug and MR which was not indeterminate.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 39 16
Measure Type: Number
Unit of Measure: percentage of participants
EOIV Number Analyzed 35 participants 16 participants
97.1 100
EOT Number Analyzed 39 participants 14 participants
97.4 100
24.Secondary Outcome
Title Percentage of Participants With Clinical Relapse at Late Follow-up (LFU) Visit: Clinically Evaluable (CE) Analysis Set at LFU
Hide Description A participant was said to have clinical relapse if met either 1 of the following criteria: reappearance or worsening of signs and symptoms of cUTI that required further antimicrobial therapy and/or surgery or death after TOC in which cUTI was contributory. LFU visit occurred within 20 to 36 days after last dose of study treatment (IV or oral).
Time Frame LFU visit (anytime up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
CE analysis set at LFU: participants >=1gram negative typical pathogen known to cause cUTI, no gram positive pathogen (in urine) at baseline, confirmed cUTI diagnosis, >=48hr of IV study drug, unless discontinued due to AE, no important protocol deviations, no concomitant antibiotic,were evaluated for clinical response of sustained cure or relapse.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 52 22
Measure Type: Number
Unit of Measure: percentage of participants
6.8 0
25.Secondary Outcome
Title Percentage of Participants With Clinical Relapse at Late Follow-up (LFU) Visit: Microbiologically Evaluable (ME) Analysis Set at LFU
Hide Description A participant was said to have clinical relapse if met either 1 of the following criteria: reappearance or worsening of signs and symptoms of cUTI that required further antimicrobial therapy and/or surgery, or death after TOC in which cUTI was contributory. LFU visit occurred within 20 to 36 days after last dose of study treatment (IV or oral).
Time Frame LFU visit (anytime up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set: participants >=1gram(-ve) and no gram(+ve) pathogen (in urine) at baseline, confirmed cUTI diagnosis, had >=48hr IV study drug, unless discontinued due to AE, no important protocol deviation, concomitant antibiotic, >=1gram(-ve) typical UTI bacterial pathogen at Baseline susceptible to study drug and MR which was not indeterminate.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 16 9
Measure Type: Number
Unit of Measure: percentage of participants
12.5 0
26.Secondary Outcome
Title Percentage of Participants With Emergent Infections: Microbiological Intent-to-treat (Micro-ITT) Population
Hide Description Emergent infections were categorized as super-infection and new infections. Superinfection: A urine culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. New infection: A urine culture identified pathogen other than a baseline pathogen at any time after study treatment had finished along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. Percentage of participants with any (super infections or new infections) of the infections were reported.
Time Frame Baseline up to 50 days
Hide Outcome Measure Data
Hide Analysis Population Description
Micro-ITT analysis population included all randomized participants who had at least 1 gram negative typical pathogen (in the urine) at baseline known to cause cUTI and no gram cUTI and no gram positive pathogen (in the urine) at baseline.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 54 23
Measure Type: Number
Unit of Measure: percentage of participants
5.6 0
27.Secondary Outcome
Title Percentage of Participants With Emergent Infections: Microbiologically Evaluable (ME) Analysis Population
Hide Description Emergent infections were categorized as super-infection and new infections. Superinfection: A urine culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. New infection: A urine culture identified pathogen other than a baseline pathogen at any time after study treatment had finished along with worsening signs and symptoms of infection requiring alternative antimicrobial therapy. Percentage of participants with any (super infections or new infections) of the infections were reported.
Time Frame Baseline up to 50 days
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set: participants >=1gram(-ve) and no gram(+ve) pathogen (in urine) at baseline, confirmed cUTI diagnosis, had >=48hr IV study drug, unless discontinued due to AE, no important protocol deviation, concomitant antibiotic, >=1gram(-ve) typical UTI bacterial pathogen at Baseline susceptible to study drug and MR which was not indeterminate.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 41 16
Measure Type: Number
Unit of Measure: percentage of participants
7.3 0
28.Secondary Outcome
Title Percentage of Participants With Favourable Combined Response: Microbiological Intent-to-treat (Micro-ITT) Population
Hide Description Combined response was the combined assessment of clinical response and microbiological response. Favorable clinical response was defined as a clinical response of improvement and cure (at EOIV) and a clinical response of cure (at TOC). Cure defined as: resolution of all acute signs/symptoms of cUTI/improvement to such an extent that no further antimicrobial therapy required. Improvement defined as: participants who switched to oral therapy and had afebrile (temperature<=38.0°C) for >=24 hr; absence of new and improvement in at least 1 symptom or sign (ie, fever, pain, tenderness, elevated WBCs, elevated CRP) from Baseline and worsening of none. Favourable microbiological response was absence of the original baseline pathogen in source specimen. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral).
Time Frame EOIV visit (Day 4 to 15), TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Micro-ITT analysis population included all randomized participants who had at least 1 gram negative typical pathogen (in the urine) at baseline known to cause cUTI and no gram cUTI and no gram positive pathogen (in the urine) at baseline.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 54 23
Measure Type: Number
Unit of Measure: percentage of participants
Favourable at EOIV 79.6 78.3
Favourable at TOC 72.2 60.9
29.Secondary Outcome
Title Percentage of Participants With Combined Response: Microbiologically Evaluable (ME) Analysis Population
Hide Description Combined response was the combined assessment of clinical response and microbiological response. Favorable clinical response was defined as a clinical response of improvement and cure (at EOIV) and a clinical response of cure (at TOC). Cure defined as: resolution of all acute signs/symptoms of cUTI/improvement to such an extent that no further antimicrobial therapy required. Improvement defined as: participants who switched to oral therapy and had afebrile (temperature<=38.0°C) for >=24 hr; absence of new and improvement in at least 1 symptom or sign (ie, fever, pain, tenderness, elevated WBCs, elevated CRP) from Baseline and worsening of none. Favourable microbiological response was absence of the original baseline pathogen in source specimen. EOIV visit occurred within 24 hours after completion of last infusion of the study drug. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral).
Time Frame EOIV visit (Day 4 to 15), TOC visit (up to a maximum study duration of 50 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ME analysis set: participants >=1gram(-ve) and no gram(+ve) pathogen (in urine) at baseline, confirmed cUTI diagnosis, had >=48hr IV study drug, unless discontinued due to AE, no important protocol deviation, concomitant antibiotic, >=1gram(-ve) typical UTI bacterial pathogen at Baseline susceptible to study drug and MR which was not indeterminate.
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description:
Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
Overall Number of Participants Analyzed 41 16
Measure Type: Number
Unit of Measure: percentage of participants
Favourable at EOIV Number Analyzed 35 participants 16 participants
97.1 100
Favourable at TOC Number Analyzed 41 participants 16 participants
80.5 68.8
Time Frame Baseline until the LFU visit (up to a maximum study duration of 50 days)
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
 
Arm/Group Title Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Hide Arm/Group Description Participants with Creatinine clearance(CrCL) >=50 milliliter per minute (mL/min) received single IV infusion of CAZ/AVI for 2 hour in following manner: 1) Age 6 to less than (<)18 years: 2000 mg CAZ/500 mg AVI (body weight >=40 kg), 50 mg/kg CAZ/12.5 mg/kg AVI (body weight <40 kg), 2) Age 6 months to <6 years: 50 mg/kg CAZ/12.5 mg/kg AVI, 3) Age 3 months to <6 months: 40 mg/kg CAZ/10 mg/kg AVI. The infusion was administered to participants every 8 hours for a minimum of 72 hours and up to a maximum duration of 14 days. Dose of CAZ-AVI was reduced to 50 percent if CrCl of participant drops below to 50mL/min, and participant was removed from study therapy, if CrCl drops below 30mL/min. After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion. Participants received intravenous (IV) infusion of cefepime, at a dose and frequency prescribed by investigator's (maximum dose of cefepime in any single infusion not exceed 2000 mg every 12 hours). After having 72 hours of IV treatment, participants had option to switch to an oral therapy at investigator's discretion.
All-Cause Mortality
Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/28 (0.00%) 
Hide Serious Adverse Events
Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Affected / at Risk (%) Affected / at Risk (%)
Total   8/67 (11.94%)   2/28 (7.14%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/67 (1.49%)  0/28 (0.00%) 
Constipation * 1  1/67 (1.49%)  0/28 (0.00%) 
Infections and infestations     
Cystitis * 1  0/67 (0.00%)  1/28 (3.57%) 
Pyelonephritis acute * 1  2/67 (2.99%)  1/28 (3.57%) 
Urinary tract infection * 1  3/67 (4.48%)  0/28 (0.00%) 
Viral infection * 1  1/67 (1.49%)  0/28 (0.00%) 
Nervous system disorders     
Nervous system disorder * 1  1/67 (1.49%)  0/28 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis * 1  1/67 (1.49%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ceftazidime- Avibactam (CAZ-AVI) Cefepime
Affected / at Risk (%) Affected / at Risk (%)
Total   13/67 (19.40%)   9/28 (32.14%) 
Gastrointestinal disorders     
Diarrhoea * 1  5/67 (7.46%)  3/28 (10.71%) 
Vomiting * 1  2/67 (2.99%)  2/28 (7.14%) 
Infections and infestations     
Rhinitis * 1  4/67 (5.97%)  2/28 (7.14%) 
Skin and subcutaneous tissue disorders     
Intertrigo * 1  1/67 (1.49%)  2/28 (7.14%) 
Rash * 1  3/67 (4.48%)  2/28 (7.14%) 
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02497781    
Other Study ID Numbers: D4280C00016
C3591005 ( Other Identifier: Alias Study Number )
2014-003244-13 ( EudraCT Number )
First Submitted: June 16, 2015
First Posted: July 15, 2015
Results First Submitted: March 12, 2018
Results First Posted: April 10, 2018
Last Update Posted: July 11, 2018