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Clinical Trial Results:
Phase III, Randomized, Multicentre, Double-blind, Double-dummy, Parallel-group Comparative Study to Determine the Efficacy, Safety And Tolerability of Ceftazidime-Avibactam (CAZ-AVI) Versus Meropenem in the Treatment of Nosocomial Pneumonia (NP) Including Ventilator-Associated Pneumonia (VAP) in Hospitalised Adults

Summary
EudraCT number	2012-004006-96
Trial protocol	CZ HU GB ES IT PL BG LV SI LT GR RO
Global end of trial date	07 Jan 2016

Results information
Results version number	v1(current)
This version publication date	06 Jan 2017
First version publication date	06 Jan 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

D4281C00001

ISRCTN number

US NCT number

NCT01808092

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca

Sponsor organisation address

AstraZeneca AB, 151 85 Södertälje, Sweden,

Public contact

MSD: Joseph Chow, AstraZeneca, Joseph.Chow@astrazeneca.com

Scientific contact

David Wilson, Statistical Team Leader - Infection, AstraZeneca, +44 1625 517830 x, David.wilson2@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

25 May 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

07 Jan 2016

Global end of trial reached?

Yes

Global end of trial date

07 Jan 2016

Was the trial ended prematurely?

Main objective of the trial

To assess the non-inferiority of ceftazidime-avibactam (CAZ-AVI) compared to meropenem with respect to clinical cure at the test of cure (TOC) visit (Day 21 - 25 from randomization) in patients in the clinically modified intent-to-treat (cMITT) population and patients in the clinically evaluable (CE) population.

Protection of trial subjects

The final study protocol, including the final version of the informed consent form and any other written information or materials provided to the patients was approved by an independent ethics committee (EC) and/or institutional review board (IRB). The investigator ensured the distribution of these documents to the applicable EC and to the study center personnel. This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Conference on Harmonisation (ICH) harmonised tripartite guideline E6(R1) Good Clinical Practice (GCP), applicable regulatory requirements, and the AstraZeneca policy on Bioethics and Human Biological Samples.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Apr 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 85

Country: Number of subjects enrolled

Bulgaria: 7

Country: Number of subjects enrolled

China: 274

Country: Number of subjects enrolled

Czech Republic: 95

Country: Number of subjects enrolled

France: 46

Country: Number of subjects enrolled

Hungary: 20

Country: Number of subjects enrolled

India: 78

Country: Number of subjects enrolled

Japan: 21

Country: Number of subjects enrolled

Korea, Republic of: 20

Country: Number of subjects enrolled

Latvia: 1

Country: Number of subjects enrolled

Mexico: 5

Country: Number of subjects enrolled

Peru: 3

Country: Number of subjects enrolled

Philippines: 28

Country: Number of subjects enrolled

Poland: 25

Country: Number of subjects enrolled

Romania: 5

Country: Number of subjects enrolled

Russian Federation: 24

Country: Number of subjects enrolled

South Africa: 1

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

Turkey: 3

Country: Number of subjects enrolled

Ukraine: 27

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Vietnam: 20

Worldwide total number of subjects

808

EEA total number of subjects

218

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

394

From 65 to 84 years

376

85 years and over

Subject disposition

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Recruitment details

Overall, 879 patients were randomized, from 4 geographic regions. The first patient was enrolled on 13 Apr. 2013 and the last patient last visit was on 07 Jan. 2016. Summary tables exclude 62 patients with moderate/severe renal impairment recruited prior to a protocol amendment to the dose regimen for such patients. 817 randomized and 808 treated.

Screening details

After obtaining written informed consent patients underwent a preliminary evaluation for eligibility within the 24-hour period prior to initiation of IV study therapy. Eligible patients were randomized to 1 of 2 treatments in a 1:1 ratio according to the randomization schedule.

Period 1 title

Prior to Study Treatment (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Data analyst, Subject

Are arms mutually exclusive

Yes

CAZ-AVI

Arm description

2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem

Arm type

Experimental

Investigational medicinal product name

Ceftazidime-Avibactam

Investigational medicinal product code

CAZ-AVI

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

• 2000mg ceftazidime / 500mg avibactam Intra-Venous (IV) infused over 2 hours plus appropriate placebo to meropenem

Meropenem

Arm description

meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo

Arm type

Active comparator

Investigational medicinal product name

Meropenem

Investigational medicinal product code

Meropenem

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

• meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo

Number of subjects in period 1	CAZ-AVI	Meropenem
Started	405	403
Completed	355	363
Not completed	50	40
Adverse event, serious fatal	37	28
Consent withdrawn by subject	8	4
Other Eligibility criteria	2	1
Lost to follow-up	3	7

Baseline characteristics

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Reporting group title

CAZ-AVI

Reporting group description

2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem

Reporting group title

Meropenem

Reporting group description

meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo

Reporting group values	CAZ-AVI	Meropenem	Total
Number of subjects	405	403	808
Age categorical
This is based on safety analysis set
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-45 years)	74	74	148
From 46-64 years	124	122	246
From 65-74 years	97	95	192
From 75-90 years	110	112	222
Age Continuous \|
Units: Years
arithmetic mean (standard deviation)	61.8 ( 16.76 )	61.7 ( 17.57 )	-
Gender, Male/Female
Units: Participants
Female	101	105	206
Male	304	298	602

End points

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Reporting group title

CAZ-AVI

Reporting group description

2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem

Reporting group title

Meropenem

Reporting group description

meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set (co-primary analyses)

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End point title

The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set (co-primary analyses)

End point description

The proportion of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.

End point type

Primary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	356	370
Units: participants
Clinical cure	245	270
Clinical failure	79	70
Indeterminate	32	30

Proportion of patients with clinical cure

Statistical analysis description

Statistical analysis for the proportion of patients with clinical cure at TOC in cMITT analysis set

Comparison groups

CAZ-AVI v Meropenem

Number of subjects included in analysis

726

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

= 0.007 ^[2]

Method

% Risk Difference (RD)

Parameter type

percentage: units for RD are %

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.76

upper limit

2.46

Notes
[1] - The statistical test of NI for the primary efficacy analysis will be performed at the 2.5% 1 sided significance level. This test will be based on the lower limit of a 2-sided 95% confidence interval (CI). Consistent with the protocol, NI will be concluded if the lower limit of the 95% CI is greater than -12.5%.
[2] - P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff <= -12.5%.

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically evaluable at TOC analysis set (co-primary analyses)

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End point title

The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically evaluable at TOC analysis set (co-primary analyses)

End point description

End point type

Primary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	257	270
Units: participants
Clinical cure	199	211
Clinical failure	58	59

Proportion of patients with clinical cure

Statistical analysis description

Statistical analysis for the proportion of patients with clinical cure at TOC in CE at TOC analysis set

Comparison groups

CAZ-AVI v Meropenem

Number of subjects included in analysis

527

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

< 0.001 ^[4]

Method

% Risk Difference (RD)

Parameter type

percentage: units for RD are %

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.86

upper limit

6.39

Notes
[3] - The statistical test of NI for the primary efficacy analysis will be performed at the 2.5% 1 sided significance level. This test will be based on the lower limit of a 2-sided 95% confidence interval (CI). Consistent with the protocol, NI will be concluded if the lower limit of the 95% CI is greater than -12.5%.
[4] - P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff <= -12.5%.

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically modified intent-to-treat analysis set

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End point title

The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically modified intent-to-treat analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Clinical cure	120	138
Clinical failure	37	34
Indeterminate	14	12

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the extended microbiologically evaluable analysis set

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End point title

The proportion of patients with clinical cure at test-of-cure (TOC) visit in the extended microbiologically evaluable analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	125	131
Units: participants
Clinical cure	96	103
Clinical failure	29	28

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically evaluable analysis set

Top of page

End point title

The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically evaluable analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	107	118
Units: participants
Clinical cure	85	94
Clinical failure	22	24

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

Top of page

End point title

The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

End point description

The proportion of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Clinical cure	143	161
Clinical failure	23	18
Indeterminate	5	5

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set

Top of page

End point title

The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	356	370
Units: participants
Clinical cure	292	309
Clinical failure	50	45
Indeterminate	14	16

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically evaluable analysis set

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End point title

The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically evaluable analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	291	306
Units: participants
Clinical cure	253	268
Clinical failure	38	38

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in extended microbiologically evaluable analysis set

Top of page

End point title

The proportion of patients with clinical cure at end of treatment (EOT) visit in extended microbiologically evaluable analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	143	151
Units: participants
Clinical cure	125	135
Clinical failure	18	16

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically evaluable analysis set

Top of page

End point title

The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically evaluable analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	122	138
Units: participants
Clinical cure	110	126
Clinical failure	12	12

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

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End point title

The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

End point description

Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Favorable	128	148
Unfavorable	38	31
Indeterminate	5	5

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

Top of page

End point title

The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Favorable	95	118
Unfavorable	64	54
Indeterminate	12	12

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

Top of page

End point title

The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	143	151
Units: participants
Favorable	112	123
Unfavorable	31	28

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

Top of page

End point title

The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	125	131
Units: participants
Favorable	80	89
Unfavorable	45	42

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

Top of page

End point title

The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	122	138
Units: participants
Favorable	96	112
Unfavorable	26	26

No statistical analyses for this end point

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

Top of page

End point title

The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	107	118
Units: participants
Favorable	70	83
Unfavorable	37	35

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥10 patients)

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End point title

The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥10 patients)

End point description

The proportion of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants with favorable responses
Enterobacter aerogenes (n=8, 8)	6	5
Enterobacter cloacae (n=26, 22)	25	20
Escherichia coli (n=17, 20)	15	18
Klebsiella pneumoniae (n=59, 71)	49	65
Proteus mirabilis (n=14, 12)	12	10
Serratia marcescens (n=15, 13)	12	11
Haemophilus influenzae (n=16, 25)	15	25
Pseudomonas aeruginosa (n=58, 47)	33	27
Staphylococcus aureus (n=24, 34)	21	32

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	143	151
Units: participants with favorable responses
Enterobacter aerogenes (n=6, 7)	4	5
Enterobacter cloacae (n=22, 17)	22	17
Escherichia coli (n=14, 18)	13	17
Klebsiella pneumoniae (n=46, 57)	39	53
Proteus mirabilis (n=9, 8)	8	6
Serratia marcescens (n=13, 10)	12	8
Haemophilus influenzae (n=14, 16)	14	16
Pseudomonas aeruginosa (n=50, 41)	30	24
Staphylococcus aureus (n=18, 26)	16	25

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	122	138
Units: participants with favorable responses
Enterobacter aerogenes (n=6, 7)	4	5
Enterobacter cloacae (n=22, 17)	22	17
Escherichia coli (n=13, 18)	13	17
Klebsiella pneumoniae (n=45, 55)	38	51
Proteus mirabilis (n=9, 8)	8	6
Serratia marcescens (n=13, 10)	12	8
Haemophilus influenzae (n=12, 15)	12	15
Pseudomonas aeruginosa (n=38, 34)	22	19
Staphylococcus aureus (n=16, 23)	14	22

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥10 patients)

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End point title

The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥10 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants with favorable responses
Enterobacter aerogenes (n=8, 8)	5	5
Enterobacter cloacae (n=26, 22)	21	13
Escherichia coli (n=17, 20)	13	16
Klebsiella pneumoniae (n=59, 71)	37	53
Proteus mirabilis (n=14, 12)	11	8
Serratia marcescens (n=15, 13)	10	8
Haemophilus influenzae (n=16, 25)	14	23
Pseudomonas aeruginosa (n=58, 47)	22	18
Staphylococcus aureus (n=24, 34)	11	25

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	125	131
Units: participants with favorable responses
Enterobacter aerogenes (n=6, 5)	5	3
Enterobacter cloacae (n=21, 11)	18	7
Escherichia coli (n=11, 18)	10	16
Klebsiella pneumoniae (n=37, 49)	29	39
Proteus mirabilis (n=11, 8)	9	6
Serratia marcescens (n=12, 8)	9	5
Haemophilus influenzae (n=11, 13)	11	12
Pseudomonas aeruginosa (n=42, 35)	18	14
Staphylococcus aureus (n=14, 22)	5	17

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	107	118
Units: participants with favorable responses
Enterobacter aerogenes (n=6, 5)	5	3
Enterobacter cloacae (n=21, 11)	18	7
Escherichia coli (n=10, 18)	10	16
Klebsiella pneumoniae (n=37, 47)	29	38
Proteus mirabilis (n=11, 8)	9	6
Serratia marcescens (n=12, 8)	9	5
Haemophilus influenzae (n=9, 12)	9	11
Pseudomonas aeruginosa (n=31, 28)	13	12
Staphylococcus aureus (n=13, 19)	4	15

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
All (n=45, 54)	40	45
Enterobacteriaceae (n=34, 41)	32	33
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 6)	6	4
Escherichia coli (n=6, 5)	5	3
Klebsiella pneumoniae (n=20, 30)	20	26
Gram- pathogens not Enterobacteriaceae (n=11,16)	8	14
Pseudomonas aeruginosa (n=11, 15)	8	13

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	291	306
Units: participants
All (n=39, 49)	35	42
Enterobacteriaceae (n=29, 37)	27	31
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 5)	6	3
Escherichia coli (n=6, 4)	5	3
Klebsiella pneumoniae (n=16, 28)	16	25
Gram- pathogens not Enterobacteriaceae (n=10,14)	8	13
Pseudomonas aeruginosa (n=10, 13)	8	12

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	122	138
Units: participants
All (n=32, 40)	31	36
Enterobacteriaceae (n=28, 35)	27	31
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 5)	6	3
Escherichia coli (n=5, 4)	5	3
Klebsiella pneumoniae (n=16, 26)	16	25
Gram- pathogens not Enterobacteriaceae (n=4,7)	4	7
Pseudomonas aeruginosa (n=4, 6)	4	6

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
All (n=45, 54)	35	40
Enterobacteriaceae (n=34, 41)	28	29
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 6)	6	4
Escherichia coli (n=6, 5)	4	3
Klebsiella pneumoniae (n=20, 30)	16	22
Gram- pathogens not Enterobacteriaceae (n=11,16)	7	13
Pseudomonas aeruginosa (n=11, 15)	7	13

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	257	270
Units: participants
All (n=36, 41)	29	32
Enterobacteriaceae (n=27, 30)	23	22
Enterobacter cloacae (n=5, 5)	5	3
Escherichia coli (n=5, 4)	4	3
Klebsiella pneumoniae (n=14, 22)	12	17
Gram- pathogens not Enterobacteriaceae (n=9,13)	6	12
Pseudomonas aeruginosa (n=9, 13)	6	12

No statistical analyses for this end point

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

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End point title

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	107	118
Units: participants
All (n=29, 32)	25	26
Enterobacteriaceae (n=26, 28)	23	22
Enterobacter cloacae (n=5, 5)	5	3
Escherichia coli (n=4, 4)	4	3
Klebsiella pneumoniae (n=14, 20)	12	17
Gram- pathogens not Enterobacteriaceae (n=3,6)	2	6
Pseudomonas aeruginosa (n=3, 6)	2	6

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit

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End point title

Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	46	54
Units: participants
Favorable	35	39
Unfavorable	10	13
Indeterminate	1	2

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

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End point title

Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	40	49
Units: participants
Favorable	31	36
Unfavorable	9	13

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

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End point title

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	33	40
Units: participants
Favorable	26	29
Unfavorable	7	11

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

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End point title

Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	46	54
Units: participants
Favorable	27	27
Unfavorable	16	23
Indeterminate	3	4

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

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End point title

Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	37	41
Units: participants
Favorable	23	21
Unfavorable	14	20

No statistical analyses for this end point

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

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End point title

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	30	32
Units: participants
Favorable	21	18
Unfavorable	9	14

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at EOT visit (pathogens in ≥5 patients)

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End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at EOT visit (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	46	54
Units: participants with favorable responses
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 6)	6	6
Escherichia coli (n=6, 5)	5	4
Klebsiella pneumoniae (n=20, 30)	18	26
Pseudomonas aeruginosa (n=11, 15)	8	7

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at EOT analysis set (pathogens in ≥5 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at EOT analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	40	49
Units: participants with favorable responses
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 5)	6	5
Escherichia coli (n=6, 4)	5	4
Klebsiella pneumoniae (n=16, 28)	14	25
Pseudomonas aeruginosa (n=10, 13)	8	6

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at EOT analysis set (pathogens in ≥5 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at EOT analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the end of treatment (EOT) visit (within 24 hours after last IV dose)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	33	40
Units: participants with favorable responses
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 5)	6	5
Escherichia coli (n=5, 4)	5	4
Klebsiella pneumoniae (n=16, 26)	14	23
Pseudomonas aeruginosa (n=4, 6)	3	1

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at TOC visit (pathogens in ≥5 patients)

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End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at TOC visit (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	46	54
Units: participants with favorable responses
Enterobacter aerogenes (n=4, 2)	3	2
Enterobacter cloacae (n=6, 6)	5	5
Escherichia coli (n=6, 5)	4	4
Klebsiella pneumoniae (n=20, 30)	15	18
Pseudomonas aeruginosa (n=11, 15)	4	4

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at TOC analysis set (pathogens in ≥5 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at TOC analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	37	41
Units: participants with favorable responses
Enterobacter cloacae (n=5, 5)	4	4
Escherichia coli (n=5, 4)	4	4
Klebsiella pneumoniae (n=14, 22)	11	14
Pseudomonas aeruginosa (n=9, 13)	3	3

No statistical analyses for this end point

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at TOC analysis set (pathogens in ≥5 patients)

Top of page

End point title

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at TOC analysis set (pathogens in ≥5 patients)

End point description

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	30	32
Units: participants with favorable responses
Enterobacter cloacae (n=5, 5)	4	4
Escherichia coli (n=4, 4)	4	4
Klebsiella pneumoniae (n=14, 20)	11	13
Pseudomonas aeruginosa (n=3, 6)	1	1

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

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End point title

The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

End point description

The proportion of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at test-of-cure visit.

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Number of patients who died (all cause mortality)	16	14
Deaths due to disease progression	6	5
Number of patients with any AE with outcome=death	10	9
Number of patients alive	153	170
Number of patients with unknown survival status	2	0

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit

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End point title

The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit

End point description

The proportion of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at test-of-cure visit.

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	356	370
Units: participants
Number of patients who died (all cause mortality)	29	25
Deaths due to disease progression	10	6
Number of patients with any AE with outcome=death	19	19
Number of patients alive	316	341
Number of patients with unknown survival status	11	4

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in the clinically evaluable at test-of-cure analysis set

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End point title

The proportion of patients with death due to any cause (all-cause mortality) at test-of-cure (TOC) visit in the clinically evaluable at test-of-cure analysis set

End point description

The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set.

End point type

Secondary

End point timeframe

At the test-of-cure (TOC) visit (Day 21 to 25)

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	257	270
Units: participants
Number of patients who died (all cause mortality)	11	8
Deaths due to disease progression	5	4
Number of patients with any AE with outcome=death	6	4
Number of patients alive	245	262
Number of patients with unknown survival status	1	0

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at day 28

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End point title

The proportion of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at day 28

End point description

The proportion of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at day 28.

End point type

Secondary

End point timeframe

at Day 28 from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Number of patients who died (all cause mortality)	17	16
Deaths due to disease progression	6	5
Number of patients with any AE with outcome=death	11	11
Number of patients alive	152	168
Number of patients with unknown survival status	2	0

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at day 28

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End point title

The proportion of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at day 28

End point description

The proportion of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at day 28.

End point type

Secondary

End point timeframe

at Day 28 from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	356	370
Units: participants
Number of patients who died (all cause mortality)	30	27
Deaths due to disease progression	10	6
Number of patients with any AE with outcome=death	20	21
Number of patients alive	315	339
Number of patients with unknown survival status	11	4

No statistical analyses for this end point

Secondary: The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set at day 28

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End point title

The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set at day 28

End point description

The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set at day 28.

End point type

Secondary

End point timeframe

at Day 28 from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	257	270
Units: participants
Number of patients who died (all cause mortality)	12	9
Deaths due to disease progression	5	4
Number of patients with any AE with outcome=death	7	5
Number of patients alive	244	261
Number of patients with unknown survival status	1	0

No statistical analyses for this end point

Secondary: The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

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End point title

The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

End point description

The proportion of patients discharged from hospital in microbiologically modified intent-to-treat analysis set.

End point type

Secondary

End point timeframe

up to 25 days from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	171	184
Units: participants
Number of patients with admission date	170	182
Number of patients with at least one discharge	71	75
1 discharge	71	74
2 discharges	0	1
>2 discharges	0	0

No statistical analyses for this end point

Secondary: The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set

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End point title

The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set

End point description

The proportion of patients discharged from hospital in the clinically modified intent-to-treat analysis set.

End point type

Secondary

End point timeframe

up to 25 days from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	356	370
Units: participants
Number of patients with admission date	355	366
Number of patients with at least one discharge	206	206
1 discharge	201	200
2 discharges	5	4
>2 discharges	0	2

No statistical analyses for this end point

Secondary: The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in the clinically evaluable at test-of-cure analysis set

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End point title

The proportion of patients discharged from hospital up to test-of-cure (TOC) visit in the clinically evaluable at test-of-cure analysis set

End point description

The proportion of patients discharged from hospital in the clinically evaluable at test-of-cure analysis set.

End point type

Secondary

End point timeframe

up to 25 days from randomization

End point values	CAZ-AVI	Meropenem
Number of subjects analysed	257	270
Units: participants
Number of patients with admission date	256	266
Number of patients with at least one discharge	148	155
1 discharge	144	151
2 discharges	4	3
>2 discharges	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Nonserious AEs and SAEs were collected for each patient from the time when informed consent was obtained at Screening (Day –1 to 0) through the final protocol follow-up (FPFU) visit.

Adverse event reporting additional description

AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF. Please note: “The section "total # of deaths resulting from adverse events" is for fatalities that are causally related to the treatment".

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Meropenem

Reporting group description

meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo. Total # Subjects Affected by Non Serious Adverse Events (with preferred terms meeting frequency threshold)

Reporting group title

CAZ-AVI

Reporting group description

2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem. Total # Subjects Affected by Non Serious Adverse Events (with preferred terms meeting frequency threshold)

Serious adverse events	Meropenem	CAZ-AVI
Total subjects affected by serious adverse events
subjects affected / exposed	54 / 403 (13.40%)	75 / 405 (18.52%)
number of deaths (all causes)	30	38
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchioloalveolar carcinoma
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to peritoneum
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Rectal cancer metastatic
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Hypertensive emergency
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 403 (0.25%)	3 / 405 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 3
Intentional medical device removal by patient
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	1 / 403 (0.25%)	3 / 405 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1
Pyrexia
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 403 (0.00%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Acute respiratory failure
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aspiration
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial secretion retention
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Bronchoplegia
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	0 / 403 (0.00%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Pleural effusion
subjects affected / exposed	3 / 403 (0.74%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 403 (0.25%)	4 / 405 (0.99%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumothorax
subjects affected / exposed	3 / 403 (0.74%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 403 (0.00%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	4 / 403 (0.99%)	5 / 405 (1.23%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 2	0 / 5
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural haemorrhage
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheostomy malfunction
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Weaning failure
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	3 / 403 (0.74%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1
Cardiac asthma
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	3 / 403 (0.74%)	4 / 405 (0.99%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 3	0 / 3
Cardiac failure acute
subjects affected / exposed	2 / 403 (0.50%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 403 (0.00%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	2 / 403 (0.50%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1
Cardiovascular insufficiency
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cyanosis
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Nervous system disorders
Autonomic nervous system imbalance
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brachial plexopathy
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrospinal fluid leakage
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	2 / 403 (0.50%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Haemorrhagic stroke
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Ischaemic stroke
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subacute hepatic failure
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 403 (0.25%)	2 / 405 (0.49%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Diabetes insipidus
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myopathy
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
CNS ventriculitis
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Clostridium difficile colitis
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	2 / 403 (0.50%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter pneumonia
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
HIV infection
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Infectious pleural effusion
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	6 / 403 (1.49%)	7 / 405 (1.73%)
occurrences causally related to treatment / all	0 / 6	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0
Pneumonia fungal
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	4 / 403 (0.99%)	5 / 405 (1.23%)
occurrences causally related to treatment / all	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 1
Septic shock
subjects affected / exposed	3 / 403 (0.74%)	3 / 405 (0.74%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 2	0 / 1
Tracheitis
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 403 (0.25%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Fluid overload
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoalbuminaemia
subjects affected / exposed	0 / 403 (0.00%)	1 / 405 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 403 (0.25%)	0 / 405 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Meropenem	CAZ-AVI
Total subjects affected by non serious adverse events
subjects affected / exposed	195 / 403 (48.39%)	198 / 405 (48.89%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	19 / 403 (4.71%)	16 / 405 (3.95%)
occurrences all number	20	16
Aspartate aminotransferase increased
subjects affected / exposed	17 / 403 (4.22%)	16 / 405 (3.95%)
occurrences all number	18	16
Vascular disorders
Hypertension
subjects affected / exposed	15 / 403 (3.72%)	14 / 405 (3.46%)
occurrences all number	16	14
Hypotension
subjects affected / exposed	8 / 403 (1.99%)	10 / 405 (2.47%)
occurrences all number	13	10
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	18 / 403 (4.47%)	24 / 405 (5.93%)
occurrences all number	21	25
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	15 / 403 (3.72%)	17 / 405 (4.20%)
occurrences all number	15	18
Pyrexia
subjects affected / exposed	13 / 403 (3.23%)	10 / 405 (2.47%)
occurrences all number	20	11
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	8 / 403 (1.99%)	10 / 405 (2.47%)
occurrences all number	8	11
Constipation
subjects affected / exposed	31 / 403 (7.69%)	25 / 405 (6.17%)
occurrences all number	38	25
Diarrhoea
subjects affected / exposed	62 / 403 (15.38%)	60 / 405 (14.81%)
occurrences all number	68	65
Nausea
subjects affected / exposed	7 / 403 (1.74%)	13 / 405 (3.21%)
occurrences all number	7	13
Vomiting
subjects affected / exposed	22 / 403 (5.46%)	23 / 405 (5.68%)
occurrences all number	24	28
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	7 / 403 (1.74%)	9 / 405 (2.22%)
occurrences all number	7	10
Skin and subcutaneous tissue disorders
Decubitus ulcer
subjects affected / exposed	6 / 403 (1.49%)	9 / 405 (2.22%)
occurrences all number	6	13
Rash
subjects affected / exposed	13 / 403 (3.23%)	8 / 405 (1.98%)
occurrences all number	13	8
Psychiatric disorders
Insomnia
subjects affected / exposed	11 / 403 (2.73%)	4 / 405 (0.99%)
occurrences all number	11	4
Infections and infestations
Urinary tract infection
subjects affected / exposed	14 / 403 (3.47%)	11 / 405 (2.72%)
occurrences all number	14	11
Metabolism and nutrition disorders
Hypokalaemia
subjects affected / exposed	33 / 403 (8.19%)	43 / 405 (10.62%)
occurrences all number	40	47
Hyponatraemia
subjects affected / exposed	6 / 403 (1.49%)	10 / 405 (2.47%)
occurrences all number	6	10

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

25 Mar 2014

1. Clarification of the visit structure and timing of visit and assessments

29 Sep 2014

1. Amendment of exclusion criteria with respect to moderate and severe renal impairment with estimated creatinine clearance (CrCl) ≤50 ml/min

09 Jan 2015

1. Re-introducing the inclusion of patients with renal impairment (creatinine clearance (CrCl) ≤ 50 ml/min).

25 Sep 2015

1. Changes to statistical methods and overall sample size of approximately 850 patients

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
20 Sep 2014	There was an interruption to recruitment of moderate or severe renal impairment at baseline patients whilst a new dosing regimen was agreed.	13 Jan 2015

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set (co-primary analyses)

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically modified intent-to-treat analysis set (co-primary analyses)

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically evaluable at TOC analysis set (co-primary analyses)

Primary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the clinically evaluable at TOC analysis set (co-primary analyses)

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the extended microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the extended microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at test-of-cure (TOC) visit in the microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in clinically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in extended microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in extended microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically evaluable analysis set

Secondary: The proportion of patients with clinical cure at end of treatment (EOT) visit in microbiologically evaluable analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

Secondary: The proportion of patients with a favorable per-patient microbiologic response at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥10 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically modified intent-to-treat analysis set at end of treatment visit (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in clinically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically modified intent-to-treat analysis set at test-of-cure visit (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in clinically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

Secondary: The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set (pathogens in ≥5 patients)

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at end of treatment visit

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at end of treatment analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically evaluable at end of treatment analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically modified intent-to-treat analysis set at test-of-cure visit

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in extended microbiologically evaluable at test-of-cure analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

Secondary: Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime at test-of-cure (TOC) visit in microbiologically evaluable at test-of-cure analysis set

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at EOT visit (pathogens in ≥5 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in microbiologically modified intent-to-treat analysis set at EOT visit (pathogens in ≥5 patients)

Secondary: The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime at end of treatment (EOT) visit in extended microbiologically evaluable at EOT analysis set (pathogens in ≥5 patients)