Clinical Trial Results:
A Phase IIa Prospective, Open-Label, Multicenter Study to Determine the Pharmacokinetics (PK) and Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) for the Treatment of Complicated Intra-Abdominal Infections (cIAIs) in Hospitalized Adults
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Summary
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EudraCT number |
2015-002726-39 |
Trial protocol |
DE ES |
Global end of trial date |
26 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Nov 2018
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First version publication date |
09 Nov 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C3601001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02655419 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Alias: D4910C00009 | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 May 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Oct 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the Pharmacokinetics (PK) and to access the safety of Aztreonam-Avibactam (ATM-AVI) in this subject population. To assess the safety of ATM-AVI in this patient population.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 May 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Spain: 34
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
29
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The study was conducted at 11 centers in 3 countries from 19-May-2016 to 26-Oct-2017. A total of 40 subjects were screened, 4 screen failures, 36 assigned to treatment and 34 received treatment. Two subjects in ATM-AVI + Metronidazole : High AVI Dose Cohort arm did not received study drug. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort | ||||||||||||||||||||||||
Arm description |
Subjects 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. Subjects also received 1 hour IV infusion of 500 mg metronidazole, every 8 hours 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. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Avibactam (AVI)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received loading dose of 137 mg of AVI, maintenance dose 410 mg AVI of lyophilisate for concentrate for solution for infusion by intravenous infusion.
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Investigational medicinal product name |
Aztreonam (ATM)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received loading dose of 500 mg of ATM, maintenance dose of 1500 mg of ATM powder for solution for infusion by intravenous infusion.
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Investigational medicinal product name |
Metronidazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received 500 mg metronidazole of solution for infusion by intravenous infusion.
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Arm title
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ATM-AVI + Metronidazole: High AVI Dose Cohort | ||||||||||||||||||||||||
Arm description |
Subjects 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. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Aztreonam (ATM)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects with CrCl >50mL/min, received loading dose of 500 mg of ATM and maintenance dose of 1500 mg. Subjects with CrCl 31-50 ml/min received loading dose of 500 mg of ATM, maintenance dose of 1500 mg followed by maintenance infusions of 750 mg of ATM powder for solution for infusion by intravenous infusion.
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Investigational medicinal product name |
Metronidazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received 500 mg metronidazole of solution for infusion by intravenous infusion.
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Investigational medicinal product name |
Avibactam (AVI)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects with CrCl >50mL/min, received loading dose of 167 mg and maintenance dose of 500 mg of AVI. Subjects with CrCl 31-50 ml/min received loading dose of 167 mg, maintenance dose of 500 mg followed by maintenance infusions of 250 mg of AVI lyophilisate for concentrate for solution for infusion by intravenous infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
All subjects who were enrolled in this study either received ATM-AVI+ Metronidazole low AVI dose cohort or ATM-AVI + Metronidazole high AVI dose cohort. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aztreonam-Avibactam(ATM-AVI)+Metronidazole:Low AVI Dose Cohort
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Reporting group description |
Subjects 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. Subjects also received 1 hour IV infusion of 500 mg metronidazole, every 8 hours 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. | ||
Reporting group title |
ATM-AVI + Metronidazole: High AVI Dose Cohort
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Reporting group description |
Subjects 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. | ||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr [1] | ||||||||||||
End point description |
All subjects were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects 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). PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analysed signifies subjects who had observations above LLOQ and "99999" signifies standard deviation was not estimable since only 1 subject had concentration above LLOQ.
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End point type |
Primary
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End point timeframe |
Predose (0 hr) on Day 1
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| Notes [2] - None of the subjects had data above LLOQ, hence, data was not reported. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr [3] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI.
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End point type |
Primary
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End point timeframe |
0.42 hr Post dose on Day 1
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr [4] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
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End point type |
Primary
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End point timeframe |
3.25 hr Post dose on Day 1
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr [5] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
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End point type |
Primary
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End point timeframe |
5 hr Post dose on Day 1
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr [6] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects 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). The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ and "99999" signifies standard deviation was not estimable since only 1 subject had concentration above LLOQ.
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End point type |
Primary
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End point timeframe |
Predose (0 hr) at Day 1
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| Notes [7] - None of the subjects had data above LLOQ, hence, data was not reported. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr [8] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
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End point type |
Primary
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End point timeframe |
0.42 hr Post dose on Day 1
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr [9] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
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End point type |
Primary
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End point timeframe |
3.25 hr Post dose on Day 1
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr [10] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
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End point type |
Primary
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End point timeframe |
5 hr Post dose on Day 1
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr [11] [12] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1)on Day4 and hence sparse data not reported.
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End point type |
Primary
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End point timeframe |
Predose (0 hr) at Day 4
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr [13] [14] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4.Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1)on Day4 and hence sparse data not reported.
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End point type |
Primary
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End point timeframe |
2.75 hr Post dose on Day 4
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr [15] [16] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1)on Day4 and hence sparse data not reported.
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End point type |
Primary
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End point timeframe |
5 hr Post dose on Day 4
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| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr [17] [18] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1) on Day 4 and hence sparse data not reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Predose (0 hr) at Day 4
|
||||||||
| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr [19] [20] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1) on Day 4 and hence sparse data not reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
2.75 hr Post dose on Day 4
|
||||||||
| Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr [21] [22] | ||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ. Intensive rather than sparse sampling was conducted for all subjects in low AVI dose cohort (Cohort 1) on Day 4 and hence sparse data not reported.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
5 hr Post dose on Day 4
|
||||||||
| Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was planned for this endpoint |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr [23] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Predose (0 hr) on Day 4
|
||||||||||||
| Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr [24] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
0.5 hr Post dose on Day 4
|
||||||||||||
| Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr [25] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
1 hr Post dose on Day 4
|
||||||||||||
| Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr [26] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 hr Post dose on Day 4
|
||||||||||||
| Notes [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr [27] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3 hr Post dose on Day 4
|
||||||||||||
| Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr [28] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.25 hr Post dose on Day 4
|
||||||||||||
| Notes [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr [29] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.5 hr Post dose on Day 4
|
||||||||||||
| Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr [30] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.75 hr Post dose on Day 4
|
||||||||||||
| Notes [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr [31] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
4 hr Post dose on Day 4
|
||||||||||||
| Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr [32] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4.Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
5 hr Post dose on Day 4
|
||||||||||||
| Notes [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr [33] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
6 hr Post dose on Day 4
|
||||||||||||
| Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr [34] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Predose (0 hr) on Day 4
|
||||||||||||
| Notes [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr [35] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
0.5 hr Post dose on Day 4
|
||||||||||||
| Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr [36] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
1 hr Post dose on Day 4
|
||||||||||||
| Notes [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr [37] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 hr Post dose on Day 4
|
||||||||||||
| Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr [38] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3 hr Post dose on Day 4
|
||||||||||||
| Notes [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr [39] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.25 hr Post dose on Day 4
|
||||||||||||
| Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr [40] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.5 hr Post dose on Day 4
|
||||||||||||
| Notes [40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr [41] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3.75 hr Post dose on Day 4
|
||||||||||||
| Notes [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr [42] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
4 hr Post dose on Day 4
|
||||||||||||
| Notes [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr [43] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
5 hr Post dose on Day 4
|
||||||||||||
| Notes [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr [44] | ||||||||||||
End point description |
All subjects were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 subjects in study were to have intensive PK sampling on Day 4 while the remaining subjects were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies subjects who had observations above LLOQ.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
6 hr Post dose on Day 4
|
||||||||||||
| Notes [44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4 [45] | ||||||||||||
End point description |
The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4 [46] | ||||||||||||
End point description |
The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Time of Observed Maximum Concentration (tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [47] | ||||||||||||||||||
End point description |
The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point 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 [48] | ||||||||||||
End point description |
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point 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 [49] | ||||||||||||
End point description |
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point 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 [50] | ||||||||||||
End point 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. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point 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 [51] | ||||||||||||
End point 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. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||
| Notes [51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Time of Last Measured Concentration (tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [52] | ||||||||||||||||||
End point description |
The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [53] | ||||||||||||||||||
End point 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. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [54] | ||||||||||||||||||
End point 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. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [54] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [55] | ||||||||||||||||||
End point 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. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4 [56] | ||||||||||||||||||
End point description |
Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes. The PK population included all subjects who had at least 1 plasma concentration data assessment available for ATM-AVI. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
|
||||||||||||||||||
| Notes [56] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||
End point title |
Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [57] | |||||||||||||||
End point description |
An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. An SAE 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 subjec or require medical intervention to prevent one of the above outcomes. Treatment-emergent AEs were events occurring between first infusion of study drug and up to late follow-up (LFU) visit (up to Study Day 38). AEs included both non-serious AEs and SAEs. The safety analysis included all enrolled subjects who received any amount of study drug.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From first dose of study drug up to the LFU visit (up to maximum of 38 days)
|
|||||||||||||||
| Notes [57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Electrocardiogram (ECG) Abnormalities [58] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Criteria for ECG abnormalities: QT value: greater than or equal to (>=) 450 milliseconds (msec), >=480 msec, >=500 msec, >=500 msec 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 msec 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. The safety analysis included all enrolled subjects who received any amount of study drug.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to EOT (up to maximum treatment duration of 15 days)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [58] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters [59] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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. The safety analysis included all enrolled subjects who received any amount of study drug. Here, Overall number of subjects analysed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to LFU visit (up to maximum of 38 days)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [59] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Parameters [60] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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. Safety analysis: all enrolled subjects who received any amount of study drug. Here, Overall number of subjects analysed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to LFU visit (up to maximum of 38 days)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [60] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Clinically Significant Vital Signs [61] | ||||||||||||||||||||||||
End point description |
Vital sign parameters included: Supine systolic blood pressure (millimeters of mercury [mmHg]), Supine diastolic blood pressure (mmHg), Heart rate (beats per min), Respiratory rate (breaths per min) and body temperature (degree celsius). Criteria for clinical significance in vital signs was based on investigator’s assessment. LFU visit occured within 20 to 24 days after last infusion. The safety analysis included all enrolled subjects who received any amount of study drug.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
From first dose of study drug up to LFU visit (up to maximum of 38 days)
|
||||||||||||||||||||||||
| Notes [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Clinical Significant Physical Examination Findings : MITT Population [62] | |||||||||||||||||||||||||||||||||||||||
End point description |
Physical examinations included an assessment of abdomen, cardiovascular, general appearance, head, eyes, ears, nose, lymph nodes, skin, musculoskeletal, neurological, respiratory systems 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. The MITT population included all enrolled subjects who received any amount of study drug. Here, ‘number analysed ’ = subjects evaluable for this endpoint at specified categories.
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
From first dose of study drug up to the LFU visit (up to maximum of 38 days)
|
|||||||||||||||||||||||||||||||||||||||
| Notes [62] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this endpoint |
||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects With Clinical Cure at Test of Cure (TOC) Visit: MITT Population | ||||||||||||
End point description |
Clinical cure was 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. The MITT population included all enrolled subjects who received any amount of study drug.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Test of Cure Visit (up to a maximum of 28 days)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population | ||||||||||||
End point description |
Clinical cure defined as complete resolution or significant improvement of signs and symptoms of 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 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. mMITT population:all enrolled subjects who had any amount of study drug, diagnosis of cIAI(that met inclusion criterion)and intraabdominal pathogen at baseline. Here, Overall number of subjects analyzed signifies those subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Test of Cure Visit (up to a maximum of 28 days)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) of Aztreonam (ATM) for Subjects With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) | ||||||||||||||||||
End point description |
AUC(0-6):area under plasma concentration-time curve from time 0upto 6hrs. Clinical cure:complete resolution/significant improvement signs&symptoms of index infection(cIAI) i.e no antimicrobial therapy,drainage/surgical intervention necessary&doesn’t meet failure criteria. Failure:death related to intraabdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting/recurrent infection within abdomen; postsurgical wound infections included open wound with signs local infection i.e purulent exudates,erythema/warmth requires additional antibiotics &/or nonroutine wound care. Data of AUC(0-6)based on intensive sampling at Day4, is reported in this endpoint separately&only for those subjects who had clinical response of cure&failure at TOC visit.TOC visit occurred upto a maximum of 28 days after first dose.MITTpopulation set used.‘n’ =subjects evaluable for this endpoint at specified categories.
|
||||||||||||||||||
End point type |
Secondary
|
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End point timeframe |
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 subjects with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) of Avibactam (AVI) for Subjects With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population) | ||||||||||||||||||
End point description |
AUC(0-6):area under plasma concentration-time curve from time 0upto 6hrs. Clinical cure:complete resolution/significant improvement signs&symptoms of index infection(cIAI) i.e no antimicrobial therapy,drainage/surgical intervention necessary&doesn’t meet failure criteria. Failure:death related to intraabdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting/recurrent infection within abdomen; postsurgical wound infections included open wound with signs local infection i.e purulent exudates,erythema/warmth requires additional antibiotics &/or nonroutine wound care. Data of AUC(0-6)based on intensive sampling at Day4, is reported in this endpoint separately&only for those subjects who had clinical response of cure&failure at TOC visit.TOCvisit occurred up to a maximum of 28 days after first dose.MITTpopulation set used.‘n’ =subjects evaluable for this endpoint at specified categories.
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End point type |
Secondary
|
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End point timeframe |
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 subjects with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
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| No statistical analyses for this end point | |||||||||||||||||||
|
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End point title |
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) of Aztreonam (ATM) for Subjects With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) | ||||||||||||||||||
End point description |
AUC(0-6):area under plasma concentration-time curve from time 0upto 6hrs. Clinical cure:complete resolution/significant improvement signs&symptoms of index infection(cIAI) i.e no antimicrobial therapy,drainage/surgical intervention necessary&doesn’t meet failure criteria. Failure:death related to intraabdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting/recurrent infection within abdomen; postsurgical wound infections included open wound with signs local infection i.e purulent exudates,erythema/warmth requires additional antibiotics &/or nonroutine wound care. Data of AUC(0-6)based on intensive sampling at Day4, is reported in this endpoint separately&only for those subjects who had clinical response of cure&failure at TOC visit. Here, 99999 signifies none of subjects had data. mMITTpopulation set used.‘n’ =subjects evaluable for this endpoint at specified categories.
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End point type |
Secondary
|
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End point timeframe |
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 subjects with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
|
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| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) of Avibactam (AVI) for Subjects With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population) | ||||||||||||||||||
End point description |
AUC(0-6):area under plasma concentration-time curve from time 0upto 6hrs. Clinical cure:complete resolution/significant improvement signs&symptoms of index infection(cIAI) i.e no antimicrobial therapy,drainage/surgical intervention necessary&doesn’t meet failure criteria. Failure:death related to intraabdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting/recurrent infection within abdomen; postsurgical wound infections included open wound with signs local infection i.e purulent exudates,erythema/warmth requires additional antibiotics &/or nonroutine wound care. Data of AUC(0-6)based on intensive sampling at Day4, is reported in this endpoint separately&only for those subjects who had clinical response of cure&failure at TOC visit. Here, 99999 signifies none of subjects had data. mMITTpopulation set used.‘n’ =subjects evaluable for this endpoint at specified categories.
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End point type |
Secondary
|
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End point timeframe |
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 subjects with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to the LFU visit (up to maximum of 38 days)
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Adverse event reporting additional description |
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Analysis was performed on safety population.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
ATM-AVI+ Metronidazole: Low AVI Dose Cohort
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Reporting group description |
Subjects 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. Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ATM-AVI + Metronidazole: High AVI Dose Cohort
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Reporting group description |
Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
05 Aug 2016 |
Addition of new sponsor study code. Describe the ATM-AVI dosing regimen for subjects with moderate renal impairment more in detail, especially with regard to the total daily doses. Updation of information on the expected end date of the study period. Clarification of pregnancy report time frame and process. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
