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Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

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ClinicalTrials.gov Identifier: NCT02655419
Recruitment Status : Completed
First Posted : January 14, 2016
Results First Posted : March 4, 2019
Last Update Posted : April 2, 2020
Sponsor:
Collaborator:
Innovative Medicines Initiative (IMI) COMBACTE-CARE
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Complicated Intra-Abdominal Infections, cIAIs
Interventions Drug: ATM-AVI
Drug: Metronidazole
Enrollment 40
Recruitment Details  
Pre-assignment Details The study was conducted at 11 centers in 3 countries from 19-May-2016 to 26-Oct-2017.
Arm/Group Title Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description Participants with normal renal function or mild renal impairment (Creatinine clearance [CrCl] greater than[>] 50 milliliter per minute [mL/min]), received intravenous (IV) infusion of 500 milligram (mg) ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator. Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Period Title: Overall Study
Started 17 23
Treated 16 18
Completed 12 16
Not Completed 5 7
Reason Not Completed
Enrolled but not treated             1             5
Withdrawal by Subject             4             1
Other             0             1
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort Total
Hide Arm/Group Description Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator. Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator. Total of all reporting groups
Overall Number of Baseline Participants 16 18 34
Hide Baseline Analysis Population Description
The modified intent-to-treat (MITT) population included all enrolled participants who received any amount of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 18 participants 34 participants
49.00  (12.47) 53.06  (14.25) 51.15  (13.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 18 participants 34 participants
Female
4
  25.0%
4
  22.2%
8
  23.5%
Male
12
  75.0%
14
  77.8%
26
  76.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 18 participants 34 participants
White
13
  81.3%
17
  94.4%
30
  88.2%
Other
1
   6.3%
0
   0.0%
1
   2.9%
Unknown
1
   6.3%
1
   5.6%
2
   5.9%
Native Hawaiian or Other Pacific Islander
1
   6.3%
0
   0.0%
1
   2.9%
1.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr
Hide Description All participants were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above lower limit of quantification (LLOQ). LLOQ for ATM was 0.1 microgram per milliliter (mcg/ml).
Time Frame Predose (0 hr) on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 1 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (mcg/mL)
0.1 [1] 
(NA%)
[1]
Standard deviation was not estimable since only 1 participant was evaluable.
2.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 0.42 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
39.0
(262.0%)
39.4
(58.1%)
3.Primary Outcome
Title Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 3.25 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
55.7
(16.0%)
58.5
(36.3%)
4.Primary Outcome
Title Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 5 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
28.8
(23.9%)
31.5
(50.8%)
5.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 nanogram per milliliter (ng/ml).
Time Frame Predose (0 hr) on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 1 0
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
24.9 [1]   (NA)
[1]
Standard deviation was not estimable since only 1 participant was evaluable.
6.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 0.42 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
7852.6
(279.2%)
9801.5
(61.8%)
7.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 3.25 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
9976.5
(25.8%)
12982.7
(49.7%)
8.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 5 hr Post dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
4086.6
(35.3%)
5549.0
(76.6%)
9.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame Predose (0 hr) on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
19.7
(29.0%)
10.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 2.75 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
46.4
(19.5%)
11.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
16.5
(37.3%)
12.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame Predose (0 hr) on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
4048.8
(24.3%)
13.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 2.75 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
9073.6
(24.2%)
14.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who had at least 1 plasma concentration data available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all participants in low AVI dose cohort(Cohort 1)on Day4 and hence sparse data not reported.
Arm/Group Title ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2745.7
(40.5%)
15.Primary Outcome
Title Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame Predose (0 hr) on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
18.3
(71.2%)
20.3
(88.5%)
16.Primary Outcome
Title Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 0.5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort Higher AVI Dose (Cohorts 2+3)
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants with cIAI, having CrCl >50mL/min, received ATM plus AVI at loading dose of 500mg ATM plus higher dose AVI(167mg), IV for 30minute period, followed by maintenance infusions of 1500mg ATM plus 500mg AVI, over 3hr period every 6hrs, for maximum of 14days. Participants with CrCl 31-50mL/min, either received loading dose consistent with Cohort 1, followed by extended loading infusion of 1500mg ATM plus 410mg AVI over 3hr period, followed by(3hrs after stop of second loading infusion) maintenance infusion of 750mg ATM plus 205mg AVI over 3hr period(administered every 6hrs) or loading dose consistent with higher AVI dose in Cohort 2, followed by extended loading infusion of 1500mg ATM plus 500mg AVI over 3hrperiod, followed by maintenance infusion of 750mg ATM plus 250mg AVI over 3hr period(administered every 6hrs). Participants also received 500mg metronidazole infused over 1hr every 8hrs after first ATM-AVI maintenance infusion(Day5 to Day14) at investigator's discretion.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
37.6
(194.0%)
33.8
(46.0%)
17.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 1 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
41.2
(53.5%)
43.0
(44.7%)
18.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 2 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
49.6
(42.5%)
53.6
(44.7%)
19.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 3 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
53.6
(72.0%)
54.7
(42.1%)
20.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 3.25 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
45.8
(36.7%)
47.3
(49.8%)
21.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 3.5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
42.9
(37.9%)
43.2
(52.1%)
22.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 3.75 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
39.5
(41.8%)
38.5
(57.6%)
23.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 4 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
34.2
(44.2%)
36.6
(63.3%)
24.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
23.8
(56.1%)
26.4
(76.8%)
25.Primary Outcome
Title Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Time Frame 6 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort Higher AVI Dose (Cohorts 2+3)
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants with cIAI, having CrCl >50mL/min, received ATM plus AVI at loading dose of 500mg ATM plus higher dose AVI(167mg), IV for 30minute period, followed by maintenance infusions of 1500mg ATM plus 500mg AVI, over 3hr period every 6hrs, for maximum of 14days. Participants with CrCl 31-50mL/min, either received loading dose consistent with Cohort 1, followed by extended loading infusion of 1500mg ATM plus 410mg AVI over 3hr period, followed by(3hrs after stop of second loading infusion) maintenance infusion of 750mg ATM plus 205mg AVI over 3hr period(administered every 6hrs) or loading dose consistent with higher AVI dose in Cohort 2, followed by extended loading infusion of 1500mg ATM plus 500mg AVI over 3hrperiod, followed by maintenance infusion of 750mg ATM plus 250mg AVI over 3hr period(administered every 6hrs). Participants also received 500mg metronidazole infused over 1hr every 8hrs after first ATM-AVI maintenance infusion(Day5 to Day14) at investigator's discretion.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
22.2
(149.8%)
19.0
(97.1%)
26.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame Predose (0 hr) on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2516.2
(85.6%)
3184.3
(137.5%)
27.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 0.5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
6374.4
(215.4%)
7140.3
(69.3%)
28.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 1 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
7369.8
(59.2%)
9435.7
(64.4%)
29.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 2 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
8885.4
(48.5%)
11668.0
(59.5%)
30.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 3 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
9820.4
(100.1%)
11903.2
(62.6%)
31.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 3.25 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
8009.9
(38.7%)
9631.5
(66.0%)
32.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 3.5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
7095.8
(43.9%)
8545.4
(83.8%)
33.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 3.75 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
6340.3
(50.3%)
7227.1
(88.4%)
34.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 4 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5258.7
(49.9%)
6727.6
(94.2%)
35.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 5 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3300.0
(59.7%)
4300.3
(120.9%)
36.Primary Outcome
Title Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr
Hide Description All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Time Frame 6 hr Post dose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies participants who had observations above LLOQ.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3275.7
(205.4%)
2879.2
(140.1%)
37.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4
Hide Description [Not Specified]
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
62.5
(146.9%)
55.4
(42.6%)
38.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4
Hide Description [Not Specified]
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
11552.4
(164.5%)
12116.2
(61.2%)
39.Primary Outcome
Title Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description [Not Specified]
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Median (Full Range)
Unit of Measure: hours
ATM
2.9
(0.5 to 3.5)
2.4
(2.0 to 3.0)
AVI
2.9
(0.5 to 3.8)
2.8
(2.0 to 3.3)
40.Primary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Aztreonam (ATM): Intensive Sampling at Day 4
Hide Description AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*microgram/milliliter (hr*mcg/mL)
235.2
(60.6%)
234.7
(54.6%)
41.Primary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Avibactam (AVI): Intensive Sampling at Day 4
Hide Description AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanogram per milliliter (hr*ng/mL)
40437.0
(74.0%)
47477.5
(79.2%)
42.Primary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Aztreonam (ATM): Intensive Sampling at Day 4
Hide Description AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*mcg/mL
235.9
(60.4%)
234.3
(54.7%)
43.Primary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Avibactam (AVI): Intensive Sampling at Day 4
Hide Description AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
40539.5  (73.8) 47422.2  (79.3)
44.Primary Outcome
Title Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description [Not Specified]
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Median (Full Range)
Unit of Measure: hours
ATM
6.0
(6.0 to 6.5)
6.0
(5.9 to 6.0)
AVI
6.0
(6.0 to 6.5)
6.0
(5.9 to 6.0)
45.Primary Outcome
Title Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description Plasma elimination half-life was defined as time measured for the plasma concentration of ATM and AVI to decrease by one half of its initial concentration.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 11 8
Mean (Standard Deviation)
Unit of Measure: hours
ATM 2.3  (1.06) 2.8  (2.05)
AVI 1.8  (0.59) 2.2  (1.85)
46.Primary Outcome
Title Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description Apparent volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 11 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter
ATM
20.3
(16.9%)
19.6
(31.8%)
AVI
26.0
(22.0%)
23.7
(29.7%)
47.Primary Outcome
Title Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 11 8
Geometric Mean (Standard Deviation)
Unit of Measure: liter
ATM 21.4  (15.3) 21.6  (24.1)
AVI 28.2  (20.4) 27.4  (20.6)
48.Primary Outcome
Title Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Hide Description Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time Frame predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter/hour
ATM
6.4
(35.4%)
6.4
(35.5%)
AVI
10.1
(42.6%)
10.5
(41.4%)
49.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAEs was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or was an important medical event which may jeopardise the participants or require medical intervention to prevent one of the above outcomes. Treatment-emergent were events between first infusion of study drug and up to late follow-up (LFU) visit (20 to 24 days after last infusion). AEs included both non-serious AEs and SAEs.
Time Frame From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis included all enrolled participants who received any amount of study drug.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
11
  68.8%
12
  66.7%
SAEs
4
  25.0%
5
  27.8%
50.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities
Hide Description Criteria for ECG abnormalities: QT value: greater than or equal to (>=) 450 milliseconds (msec), >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT: >=30 msec, >=60 msec. Decrease from baseline in QT: >=30 msec, >=60 msec. QTcB value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT interval using Bazett's correction (QTcB) value: >=30 msec, >=60 msec. Decrease from baseline in QTcB: >=30 msec, >=60 msec. QT interval using Fridericia's correction (QTcF) value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QTcF value: >=30 msec, >=60 msec. Decrease from baseline in QTcF value: >=30 msec, >=60 msec. EOT (end of treatment) visit occurred within 24 hours after last infusion.
Time Frame Baseline up to EOT (up to a maximum of 15 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis included all enrolled participants who received any amount of study drug.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Measure Type: Count of Participants
Unit of Measure: Participants
QT value >=450
2
  12.5%
0
   0.0%
QT value >=480
2
  12.5%
0
   0.0%
QT value >=500
2
  12.5%
0
   0.0%
QT value >=500 and increase from baseline >=60
1
   6.3%
0
   0.0%
Increase in QT >=30
6
  37.5%
4
  22.2%
Increase in QT>=60
2
  12.5%
1
   5.6%
Decrease in QT >=30
1
   6.3%
1
   5.6%
Decrease in QT>=60
0
   0.0%
1
   5.6%
QTcB value >=450
5
  31.3%
1
   5.6%
QTcB value >=480
2
  12.5%
0
   0.0%
QTcB value >=500
1
   6.3%
0
   0.0%
QTcB value >=500 and increase from baseline >=60
0
   0.0%
0
   0.0%
Increase in QTcB >=30
3
  18.8%
1
   5.6%
Increase in QTcB >=60
0
   0.0%
1
   5.6%
Decrease in QTcB >=30
2
  12.5%
1
   5.6%
Decrease in QTcB >=60
0
   0.0%
0
   0.0%
QTcF value >=450
4
  25.0%
0
   0.0%
QTcF value >=480
2
  12.5%
0
   0.0%
QTcF value >=500
1
   6.3%
0
   0.0%
QTcF value >=500 and increase from baseline >=60
0
   0.0%
0
   0.0%
Increase in QTcF >=30
3
  18.8%
2
  11.1%
Increase in QTcF >=60
0
   0.0%
0
   0.0%
Decrease in QTcF >=30
0
   0.0%
1
   5.6%
Decrease in QTcF >=60
0
   0.0%
0
   0.0%
51.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters
Hide Description Criteria for abnormality: Hemoglobin, hematocrit, erythrocytes less than(<) 0.7*lower limit of normal [LLN] and (&) greater than (>) 30 percent (%) below baseline [BB]; >1.3*upper limit of normal [ULN] & >30% above baseline [AB], leukocytes <0.65*LLN & >60% BB; >1.6* ULN & >100% AB; platelets <0.65*LLN & >50% BB; >1.5*ULN & >100% AB; neutrophils <0.65*LLN & >75% BB; >1.6*ULN & >100% AB, lymphocytes <0.25*LLN & >75%BB; >1.5*ULN & >100% AB, basophils, eosinophils, monocytes>4.0*ULN & >300% AB. LFU visit occurred within 20 to 24 days after last infusion.
Time Frame Baseline up to LFU visit (up to maximum of 38 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis included all enrolled participants who received any amount of study drug. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 17
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin: <0.7*LLN&>30% BB
0
   0.0%
0
   0.0%
Hemoglobin: >1.3*ULN&>30% AB
0
   0.0%
0
   0.0%
Hematocrit: <0.7*LLN&>30% BB
0
   0.0%
0
   0.0%
Hematocrit:>1.3*ULN&>30% AB
0
   0.0%
0
   0.0%
Erythrocytes:<0.7*LLN&>30% BB
0
   0.0%
0
   0.0%
Erythrocytes: >1.3*ULN&>30% AB
0
   0.0%
0
   0.0%
Leukocytes: <0.65*LLN&>60%BB
0
   0.0%
0
   0.0%
Leukocytes:>1.6* ULN&>100%AB
1
   7.7%
0
   0.0%
Platelets: <0.65*LLN&>50%BB
0
   0.0%
0
   0.0%
Platelets: >1.5*ULN&>100% AB
1
   7.7%
5
  29.4%
Neutrophils:<0.65*LLN&>75% BB
0
   0.0%
0
   0.0%
Neutrophils: >1.6*ULN & >100% AB
1
   7.7%
1
   5.9%
Lymphocytes: <0.25*LLN&>75%BB
0
   0.0%
0
   0.0%
Lymphocytes: >1.5*ULN&>100%AB
0
   0.0%
0
   0.0%
Basophils: >4.0*ULN&>300% AB
0
   0.0%
0
   0.0%
Eosinophils: >4.0*ULN&>300% AB
0
   0.0%
0
   0.0%
Monocytes: >4.0*ULN&>300% AB
0
   0.0%
0
   0.0%
52.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres
Hide Description Criteria for abnormality: aspartate aminotransferase, alanine aminotransferase >3.0*ULN & >100% AB, alkaline phosphatase <0.5 *LLN & >80% BB&; >3.0*ULN & >100% AB; bilirubin >1.5*ULN & >100% AB; direct bilirubin >2.0*ULN & >150% AB; protein <0.5*LLN & >50%BB; >1.5*ULN & >50% AB, albumin <0.5*LLN & >50% BB; >1.5*ULN & >50% AB, urea nitrogen <0.2* LLN & >100% BB; >3.0*ULN & >200% AB, creatinine >2.0*ULN & >100% AB, sodium <0.85*LLN & >10% BB;>1.1*ULN &>10% AB; potassium <0.8*LLN &>20% BB; >1.2*ULN &>20% AB, chloride <0.8*LLN &>20% BB;>1.2*ULN & >20% AB, calcium <0.7*LLN & >30% BB; >1.3*ULN & >30% AB, phosphate <0.5*LLN & >50% BB; >3.0*ULN & >200% AB, bicarbonate <0.7*LLN & >40% BB; >1.3*ULN & >40% AB, glucose <0.6*LLN & >40% BB, >3.0*ULN & >200% AB. LFU visit occurred within 20 to 24 days after last infusion.
Time Frame Baseline up to LFU visit (up to maximum of 38 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis included all enrolled participants who received any amount of study drug. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 13 17
Measure Type: Count of Participants
Unit of Measure: Participants
Aspartate aminotransferase: >3.0*ULN&>100% AB
1
   7.7%
0
   0.0%
Alanine aminotransferase:>3.0x ULN
2
  15.4%
2
  11.8%
Alkaline phosphatase: <0.5 *LLN&>80% BB&
0
   0.0%
0
   0.0%
Alkaline phosphatase:>3.0*ULN&>100%AB
0
   0.0%
0
   0.0%
Bilirubin: >1.5*ULN&>100%AB
0
   0.0%
0
   0.0%
Direct Bilirubin : >2.0*ULN&>150% AB
0
   0.0%
0
   0.0%
Protein: <0.5*LLN &>50%BB
0
   0.0%
0
   0.0%
Protein: >1.5*ULN&>50% AB
0
   0.0%
0
   0.0%
Albumin: <0.5*LLN&>50%BB
0
   0.0%
0
   0.0%
Albumin: >1.5*ULN&>50%AB
0
   0.0%
0
   0.0%
Urea nitrogen: <0.2* LLN&>100%BB
0
   0.0%
0
   0.0%
Urea nitrogen: >3.0*ULN&>200%AB
0
   0.0%
0
   0.0%
Creatinine: >2.0*ULN&>100%AB
0
   0.0%
0
   0.0%
Sodium: < 0.85*LLN&>10%BB
0
   0.0%
0
   0.0%
Sodium: >1.1*ULN&>10%AB
0
   0.0%
0
   0.0%
Potassium: <0.8*LLN&>20%BB
1
   7.7%
1
   5.9%
Potassium: >1.2*ULN&>20%AB
0
   0.0%
0
   0.0%
Chloride: <0.8*LLN&>20%BB
0
   0.0%
0
   0.0%
Chloride: >1.2*ULN&>20%AB
0
   0.0%
0
   0.0%
Calcium: <0.7*LLN&>30% BB
0
   0.0%
0
   0.0%
Calcium: >1.3*ULN&>30%AB
0
   0.0%
0
   0.0%
Phosphate: <0.5*LLN&>50% BB
0
   0.0%
0
   0.0%
Phosphate: >3.0*ULN&>200% AB
0
   0.0%
0
   0.0%
Bicarbonate: <0.7*LLN&>40% BB
0
   0.0%
0
   0.0%
Bicarbonate: >1.3*ULN&>40%AB
0
   0.0%
0
   0.0%
Glucose: <0.6*LLN&>40% BB
0
   0.0%
0
   0.0%
Glucose: >3.0*ULN&>200%AB
0
   0.0%
0
   0.0%
53.Primary Outcome
Title Number of Participants With Clinically Significant Vital Signs
Hide Description Vital sign parameters included: Supine systolic blood pressure (millimeters of mercury [mmHg]), Supine diastolic blood pressure (mmHg), Heart rate (beats per minute), Respiratory rate (breaths per minute) and body temperature (degree celsius). Criteria for clinical significance in vital signs was based on investigator's assessment. LFU visit occurred within 20 to 24 days after last infusion.
Time Frame From first dose of study drug up to LFU visit (up to maximum of 38 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis included all enrolled participants who received any amount of study drug.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Measure Type: Count of Participants
Unit of Measure: Participants
Supine systolic blood pressure
0
   0.0%
0
   0.0%
Supine diastolic blood pressure
0
   0.0%
0
   0.0%
Heart rate
0
   0.0%
0
   0.0%
Respiratory rate
0
   0.0%
1
   5.6%
Temperature
0
   0.0%
0
   0.0%
54.Primary Outcome
Title Number of Participants With Clinical Significant Physical Examination Findings : MITT Population
Hide Description Physical examinations included an assessment of abdomen, cardiovascular, general appearance, head, eyes, ears, nose, lymph nodes, skin, musculoskeletal, neurological, respiratory systems and other (edemas). Clinically significant abnormality in physical examination was based on investigator's assessment. LFU visit occured within 20 to 24 days after last infusion.
Time Frame From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all enrolled participants who received any amount of study drug. Here, 'number analysed' = Participants evaluable for this outcome measure at specified categories.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Measure Type: Count of Participants
Unit of Measure: Participants
Abdomen Number Analyzed 13 participants 17 participants
1
   7.7%
0
   0.0%
Cardiovascular Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
General appearance Number Analyzed 13 participants 17 participants
0
   0.0%
1
   5.9%
Head, Eyes, Ears, Nose Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
Lymph nodes Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
Musculoskeletal system Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
Neurological system Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
Other Number Analyzed 3 participants 2 participants
0
   0.0%
1
  50.0%
Respiratory system Number Analyzed 13 participants 17 participants
0
   0.0%
1
   5.9%
Skin Number Analyzed 13 participants 17 participants
0
   0.0%
0
   0.0%
55.Secondary Outcome
Title Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population
Hide Description Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all enrolled participants who received any amount of study drug.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.5
(35.4 to 84.8)
55.6
(30.8 to 78.5)
56.Secondary Outcome
Title Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population
Hide Description Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The mMITT population included all enrolled participants who had any amount of study drug and had a diagnosis of cIAI (that is,met inclusion criterion ) and an intraabdominal pathogen at baseline. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
Arm/Group Title ATM-AVI + Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
66.7
(34.9 to 90.1)
54.5
(23.4 to 83.3)
57.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
Hide Description AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all enrolled participants who received any amount of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*mcg/mL
Clinical Cure Number Analyzed 10 participants 4 participants
226.0
(43.0%)
218.7
(28.5%)
Clinical Failure Number Analyzed 3 participants 2 participants
268.9
(88.3%)
169.8
(14.9%)
58.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
Hide Description AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all enrolled participants who received any amount of study drug. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 16 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
Clinical Cure Number Analyzed 10 participants 4 participants
38003.8
(45.7%)
40314.0
(36.1%)
Clinical Failure Number Analyzed 3 participants 2 participants
49730.0
(100.1%)
34633.7
(10.2%)
59.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
Hide Description AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
mMITTpopulation set was used in this analysis. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.
Arm/Group Title ATM-AVI+ Metronidazole:Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*mcg/mL
Clinical Cure Number Analyzed 8 participants 1 participants
245.3
(41.4%)
292.7 [1] 
(NA%)
Clinical Failure Number Analyzed 2 participants 0 participants
378.0
(77.0%)
[1]
Standard deviation was not estimable since only 1 participant was evaluable.
60.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
Hide Description AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Time Frame Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
mMITTpopulation set was used in this analysis. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified categories. AUC0-6 was assessed on Day 4 and presented in this OM, only for those participants who had clinical cure or failure at TOC visit.
Arm/Group Title ATM-AVI+ Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description:
Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
Overall Number of Participants Analyzed 12 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
Clinical Cure Number Analyzed 8 participants 1 participants
42401.9
(41.9%)
60302.1 [1] 
(NA%)
Clinical Failure Number Analyzed 2 participants 0 participants
75509.9
(84.3%)
[1]
Standard deviation was not estimable since only 1 participant was evaluable.
Time Frame From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Adverse Event Reporting Description Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
 
Arm/Group Title ATM-AVI+ Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Hide Arm/Group Description Participants with normal renal function or mild renal impairment (CrCl > 50 mL/min), received IV infusion of 500 mg ATM plus 137 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 410 mg AVI, over a 3 hour period every 6 hours, for a minimum of 5 days and up to maximum of 14 days. Participants also received 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion for a minimum of 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator. Participants received ATM-AVI IV infusion in following manner (1. normal renal function or mild renal impairment [CrCl >50mL/min] : 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by maintenance infusions of 1500 mg ATM plus 500 mg AVI, over a 3 hour period every 6 hours; 2. moderate renal impairment [CrCl 31-50 ml/min]: 500 mg ATM plus 167 mg AVI over 30 minutes as loading dose, followed by IV extended loading infusion of 1500 mg ATM plus 500 mg AVI over 3 hour, followed by maintenance infusions of 750 mg ATM plus 250 mg AVI, over 3 hour period every 6 hours) along with 1 hour IV infusion of 500 mg metronidazole, every 8 hrs after first ATM-AVI maintenance infusion. All treatments were administered for minimum 5 days and up to maximum of 14 days. All study therapies could be discontinued (after at least 5 full days of IV therapy) at the discretion of the investigator.
All-Cause Mortality
ATM-AVI+ Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   1/18 (5.56%) 
Hide Serious Adverse Events
ATM-AVI+ Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Affected / at Risk (%) Affected / at Risk (%)
Total   4/16 (25.00%)   5/18 (27.78%) 
Gastrointestinal disorders     
Intestinal ischaemia * 1  0/16 (0.00%)  1/18 (5.56%) 
Intra-abdominal haematoma * 1  0/16 (0.00%)  1/18 (5.56%) 
Pancreatitis acute * 1  0/16 (0.00%)  1/18 (5.56%) 
Infections and infestations     
Abdominal wall infection * 1  1/16 (6.25%)  0/18 (0.00%) 
Sepsis * 1  1/16 (6.25%)  0/18 (0.00%) 
Injury, poisoning and procedural complications     
Arterial injury * 1  0/16 (0.00%)  1/18 (5.56%) 
Postoperative ileus * 1  0/16 (0.00%)  1/18 (5.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer * 1  1/16 (6.25%)  0/18 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  0/16 (0.00%)  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  1/16 (6.25%)  0/18 (0.00%) 
Respiratory distress * 1  1/16 (6.25%)  0/18 (0.00%) 
Skin and subcutaneous tissue disorders     
Haemorrhage subcutaneous * 1  0/16 (0.00%)  1/18 (5.56%) 
1
Term from vocabulary, MedDRA v20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ATM-AVI+ Metronidazole: Low AVI Dose Cohort ATM-AVI + Metronidazole: High AVI Dose Cohort
Affected / at Risk (%) Affected / at Risk (%)
Total   10/16 (62.50%)   10/18 (55.56%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/16 (6.25%)  2/18 (11.11%) 
Thrombocytosis * 1  1/16 (6.25%)  0/18 (0.00%) 
Cardiac disorders     
Cardiac failure congestive * 1  1/16 (6.25%)  0/18 (0.00%) 
Eye disorders     
Vision blurred * 1  0/16 (0.00%)  1/18 (5.56%) 
Gastrointestinal disorders     
Abdominal pain lower * 1  0/16 (0.00%)  2/18 (11.11%) 
Diarrhoea * 1  2/16 (12.50%)  3/18 (16.67%) 
Nausea * 1  0/16 (0.00%)  2/18 (11.11%) 
Paraesthesia oral * 1  1/16 (6.25%)  0/18 (0.00%) 
General disorders     
Generalised oedema * 1  1/16 (6.25%)  0/18 (0.00%) 
Oedema * 1  0/16 (0.00%)  2/18 (11.11%) 
Hepatobiliary disorders     
Drug-induced liver injury * 1  1/16 (6.25%)  0/18 (0.00%) 
Hypertransaminasaemia * 1  0/16 (0.00%)  1/18 (5.56%) 
Infections and infestations     
Chronic hepatitis C * 1  1/16 (6.25%)  0/18 (0.00%) 
Pneumonia * 1  0/16 (0.00%)  1/18 (5.56%) 
Tooth abscess * 1  1/16 (6.25%)  0/18 (0.00%) 
Injury, poisoning and procedural complications     
Limb injury * 1  0/16 (0.00%)  1/18 (5.56%) 
Investigations     
Hepatic enzyme increased * 1  7/16 (43.75%)  2/18 (11.11%) 
Metabolism and nutrition disorders     
Hyperuricaemia * 1  1/16 (6.25%)  0/18 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/16 (6.25%)  0/18 (0.00%) 
Nervous system disorders     
Dizziness * 1  0/16 (0.00%)  1/18 (5.56%) 
Psychiatric disorders     
Confusional state * 1  1/16 (6.25%)  0/18 (0.00%) 
Hallucination, visual * 1  1/16 (6.25%)  0/18 (0.00%) 
Reproductive system and breast disorders     
Testicular swelling * 1  1/16 (6.25%)  0/18 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis atopic * 1  0/16 (0.00%)  1/18 (5.56%) 
Rash * 1  1/16 (6.25%)  0/18 (0.00%) 
Skin exfoliation * 1  1/16 (6.25%)  0/18 (0.00%) 
1
Term from vocabulary, MedDRA v20.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02655419    
Other Study ID Numbers: D4910C00009
C3601001 ( Other Identifier: Alias Study Number )
2015-002726-39 ( EudraCT Number )
First Submitted: December 1, 2015
First Posted: January 14, 2016
Results First Submitted: October 24, 2018
Results First Posted: March 4, 2019
Last Update Posted: April 2, 2020