To Investigate the Safety and Tolerability of Aztreonam-A... | NCT01689207 | Trialant
NCT01689207
Sponsor
Pfizer
Status
Completed
Last Update Posted
Sep 6, 2017Actual
Enrollment
222Actual
Phase
Phase 1
Conditions
Complicated Infection
Bacterial Infections
Interventions
Avibactam (AVI)
Aztreonam (ATM)
combination of Aztreonam - Avibactam (ATM-AVI)
Placebo
Countries
United Kingdom
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
NCT01689207
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
D4910C00001
Secondary IDs
Not provided
Brief Title
To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)
Official Title
A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and Avibactam Given Alone and in Combination (ATM-AVI)
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Aug 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 2012
Primary Completion Date
Dec 2014Actual
Completion Date
Dec 2014Actual
First Submitted Date
Sep 12, 2012
First Submission Date that Met QC Criteria
Sep 20, 2012
First Posted Date
Sep 21, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 14, 2015
Results First Submitted that Met QC Criteria
Sep 6, 2016
Results First Posted Date
Oct 26, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 31, 2017
Last Update Posted Date
Sep 6, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This is a randomised, double-blind, 3-part study designed to investigate the safety and tolerability of ATM-AVI. The study aims to characterise the pharmacokinetics of ATM-AVI, when both drugs are administered alone (ATM or AVI) and in combination (ATM-AVI), following single administration, and following multiple administrations of ATM-AVI in healthy male and female (females of nonchildbearing potential) volunteers both young and elderly.
Detailed Description
A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and Avibactam given Alone and in Combination (ATM-AVI)
Conditions Module
Conditions
Complicated Infection
Bacterial Infections
Keywords
Phase I, Safety, tolerability, healthy.
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
222Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Drug: A
Experimental
Avibactam (AVI)
Drug: Avibactam (AVI)
Drug: B
Experimental
Aztreonam (ATM)
Drug: Aztreonam (ATM)
Drug: C
Experimental
combination of Aztreonam-Avibactam (ATM-AVI)
Drug: combination of Aztreonam - Avibactam (ATM-AVI)
Drug: D
Placebo Comparator
Matching Placebo
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Avibactam (AVI)
Drug
PART A: AVI IV infusion
Drug: A
Aztreonam (ATM)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Safety Profile - Number of Subjects With at Least 1 AE
from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)
Secondary Outcomes
Measure
Description
Time Frame
PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated, written informed consent prior to any study specific procedures
Healthy young male and female volunteers aged 18 to 45 years (inclusive) and healthy elderly volunteers aged 65 or older (Part C) with suitable veins for cannulation or repeated venipuncture
Have a body mass index (BMI) between 19 and 30 kg/m2
Be able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the PI
Exclusion Criteria:
History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
Known history of severe allergy to betalactam and/or L-arginine
History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to ATM or AVI
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of IP
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
130 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Frans van den Berg, MD
Hammersmith Medicines Research Cumberland Avenue Park Royal London NW10 7EW, England Telephone: +44 020 8961 4130 Fax: +44 020 8961 8665
Das S, Riccobene T, Carrothers TJ, Wright JG, MacPherson M, Cristinacce A, McFadyen L, Xie R, Luckey A, Raber S. Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation. Eur J Clin Pharmacol. 2024 Apr;80(4):529-543. doi: 10.1007/s00228-023-03609-x. Epub 2024 Jan 22.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
A Screening visit was conducted within 28 days before admission to the study centre. 222 volunteers were screend, 92 volunteers were entered into the study. Healthy volunteers were admitted to the study centre on Day -1 of either Part A, Part B or Part C.
Recruitment Details
First subject enrolled 27 September 2012 and last subject last visit was 30 December 2014. Subjects were healthy male and female volunteers both young and elderly. Healthy volunteers were given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study and could discontinue at any time.
Safety Profile - Number of Subjects With at Least 1 AE
from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Safety population
Posted
Number
Participants
Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)
from screening visit (Day -28) to follow up visit (FUP).
Description
FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: Placebo
Placebo
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pneumonia
Infections and infestations
MedDRA version 15.1
Systematic Assessment
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
More Info Module
Limitations and Caveats
No formal statistical hypothesis testing was performed. The analyses of safety, tolerability, and pharmacokinetic data were summarised descriptively including tables, listings, and graphs, as appropriate.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Point of Contact
Title
Organization
Phone
Extension
Email
Paul Newell, Medical Science Director
AstraZeneca
+44 1625 515727
paul.newell@astrazeneca.com
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
ID
Term
D001424
Bacterial Infections
Ancestor Terms
ID
Term
D001423
Bacterial Infections and Mycoses
D007239
Infections
Browse Leaves
Not provided
Browse Branches
Not provided
Intervention Browse Module
MeSH Terms
ID
Term
C543519
avibactam
D001398
Aztreonam
Ancestor Terms
ID
Term
D008997
Monobactams
D047090
beta-Lactams
D007769
Lactams
D000577
Amides
D009930
Browse Leaves
Not provided
Browse Branches
Not provided
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Basic Science
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Drug
PART A: ATM IV infusion
Drug: B
combination of Aztreonam - Avibactam (ATM-AVI)
Drug
PART A: ATM-AVI IV infusion. PART B and C: ATM-AVI IV infusions.
Drug: C
Placebo
Drug
PART A, PART B, PART C: matching placebo IV infusions
Drug: D
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C
Time to Cmax (tmax)
Day 1
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Volume of distribution at steady state (Vss).
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
8 subjects
Subjects completed study
FG0042 subjectsSubjects completed study
FG0057 subjectsSubjects completed study
FG00610 subjectsSubjects completed study
FG00710 subjectsSubjects completed study
FG0085 subjectsSubjects completed study
FG00910 subjectsSubjects completed study
FG0108 subjectsSubjects completed study
2 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
FG0100 subjects
0 subjects
FG0042 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
FG0100 subjects
BG002
Part B: Placebo
Placebo
BG003
Part B: Cohort 1 Drug
ATM (2000mg) + AVI (375mg)
BG004
Part B: Cohort 2 Drug
ATM (2000mg) + AVI (600mg)
BG005
Part B: Cohort 3 Drug
ATM (1500mg) + AVI (600mg)
BG006
Part B: Cohort 4 Drug
ATM (1500mg) + AVI (450mg)
BG007
Part B: Cohort 5 Drug
ATM (1500mg) + AVI (410mg)
BG008
Part C: Placebo
Placebo
BG009
Part C: Cohort 1 Drug
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
BG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
BG011
Total
Total of all reporting groups
4
BG0018
BG00216
BG0038
BG0044
BG0058
BG00610
BG00710
BG0086
BG00910
BG0108
BG01192
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00033.8± 6.9
BG00131.3± 7.1
BG00227.4± 5.0
BG00330.3± 4.9
BG00427.8± 1.9
BG00529.4± 9.9
BG00629.7± 7.3
BG00730.6± 6.3
BG00851.3± 19.4
BG00932.9± 8.4
BG01068.5± 2.9
BG01134.8± 14.0
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0081
BG0090
BG0102
BG0113
Male
BG0004
BG0018
BG00216
BG0038
BG004
OG002
Part B: Placebo
Placebo
OG003
Part B: Cohort 1 Drug
ATM (2000mg) + AVI (375mg)
OG004
Part B: Cohort 2 Drug
ATM (2000mg) + AVI (600mg)
OG005
Part B: Cohort 3 Drug
ATM (1500mg) + AVI (600mg)
OG006
Part B: Cohort 4 Drug
ATM (1500mg) + AVI (450mg)
OG007
Part B: Cohort 5 Drug
ATM (1500mg) + AVI (410mg)
OG008
Part C: Placebo
Placebo
OG009
Part C: Cohort 1 Drug
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
OG011
Part A: Aztreonam (ATM) 2000mg
Crossover period ATm 2000mg
OG012
Part A: Avibactam (AVI) 600mg
Crossover period AVI 600mg
OG013
Part A: ATM 2000mg + AVI 600mg
Crossover period ATM 2000mg + AVI 600mg
Units
Counts
Participants
OG0004
OG0018
OG00216
OG0038
OG0044
OG0058
OG00610
OG00710
OG0086
OG00910
OG0108
OG0117
OG0128
OG0137
Title
Denominators
Categories
Number of subjects with at least 1 AE
Title
Measurements
OG0001
OG0012
OG0023
OG0034
OG0042
OG0056
OG0068
OG0073
OG0083
OG0095
OG0107
OG0110
OG0122
OG0130
Subjects with at least 1 AE with outcome of death
Title
Measurements
OG0000
OG0010
OG0020
OG003
At least 1 AE leading to discontinuation
Title
Measurements
OG0000
OG0011
OG0020
OG003
Secondary
PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness.
Posted
Geometric Mean
Geometric Coefficient of Variation
ug*h/mL
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Units
Counts
Participants
OG0004
OG0018
OG00216
OG003
Title
Denominators
Categories
AUC (ug*h/mL) - Aztreonam (ATM) alone
Title
Measurements
OG000NA± NANot evaluated
OG001372± 15.2
OG002NA± NANot evaluated
Secondary
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)
Posted
Geometric Mean
Geometric Coefficient of Variation
h
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Units
Counts
Participants
OG0004
OG0018
OG00216
OG003
Title
Denominators
Categories
t1/2 (h) - Aztreonam (ATM) alone
Title
Measurements
OG000NA± NANot evaluated
OG0011.98± 18.9
OG002NA± NANot evaluated
Secondary
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C
Time to Cmax (tmax)
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Units
Counts
Participants
OG0004
OG0018
OG00216
OG003
Title
Denominators
Categories
tmax (h) - ATM alone
Title
Measurements
OG000NA(NA to NA)Not evaluated
OG0010.98(0.98 to 0.98)
OG002NA(NA to NA)Not evaluated
Secondary
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)
Posted
Geometric Mean
Geometric Coefficient of Variation
ug/mL
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Units
Counts
Participants
OG0004
OG0018
OG00216
OG003
Title
Denominators
Categories
Cmax (ug/mL) - ATM alone
Title
Measurements
OG000NA± NANot evaluated
OG001143± 14.0
OG002NA± NANot evaluated
Secondary
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)
Posted
Geometric Mean
Geometric Coefficient of Variation
L/h
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
OG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Units
Counts
Participants
OG0004
OG0018
OG00216
OG003
Title
Denominators
Categories
CL (L/h) - ATM alone
Title
Measurements
OG000NA± NANot evaluated
OG0015.37± 15.2
OG002NA± NANot evaluated
Secondary
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Volume of distribution at steady state (Vss).
Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in <3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)
Posted
Geometric Mean
Geometric Coefficient of Variation
L
0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)
0
10
5
10
EG010
Part C: Cohort 2 Drug
Aged >65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
0
8
7
8
EG011
Part A: Aztreonam (ATM) 2000mg
Crossover period ATM 2000mg
0
7
0
7
EG012
Part A: Avibactam (AVI) 600mg
Crossover period AVI 600mg
0
8
2
8
EG013
Part A: ATM 2000mg + AVI 600mg
Crossover period ATM 2000mg + AVI 600mg
0
7
0
7
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0081 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0032 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0062 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0104 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Abdominal distension
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0061 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Abdominal discomfort
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0071 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Dry mouth
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Frequent bowel movements
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0051 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Oral pain
Gastrointestinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Catheter site pain
General disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0071 affected10 at risk
EG0081 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Fatigue
General disorders
MedDRA version 15.1
Systematic Assessment
EG0001 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Infusion site reaction
General disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0071 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Catheter site erythema
General disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Catheter site haematoma
General disorders
MedDRA version 15.1
Systematic Assessment
EG0001 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Catheter site oedema
General disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Infusion site pain
General disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Seasonal allergy
Immune system disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0061 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Candidiasis
Infections and infestations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0021 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Otitis externa
Infections and infestations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0021 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Rhinitis
Infections and infestations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0061 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Liver function test abnormal
Investigations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0042 affected4 at risk
EG0053 affected8 at risk
EG0063 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Neutrophil count decreased
Investigations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0051 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Transaminases increased
Investigations
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0051 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Hyperamylasaemia
Metabolism and nutrition disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0121 affected8 at risk
EG0130 affected7 at risk
Back pain
Musculoskeletal and connective tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0021 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0062 affected10 at risk
EG0071 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0081 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Headache
Nervous system disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0061 affected10 at risk
EG0071 affected10 at risk
EG0082 affected6 at risk
EG0090 affected10 at risk
EG0102 affected8 at risk
EG0110 affected7 at risk
EG0121 affected8 at risk
EG0130 affected7 at risk
Dizziness
Nervous system disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0021 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Dysgeusia
Nervous system disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0031 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Paraesthesia
Nervous system disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Pollakiuria
Renal and urinary disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0051 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Skin irritation
Skin and subcutaneous tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0021 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0062 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Blister
Skin and subcutaneous tissue disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Phlebitis
Vascular disorders
MedDRA version 15.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0091 affected10 at risk
EG0101 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Hot flush
Vascular disorders
MedDRA version 15.1
Systematic Assessment
EG0001 affected4 at risk
EG0010 affected8 at risk
EG0020 affected16 at risk
EG0030 affected8 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected10 at risk
EG0070 affected10 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected8 at risk
EG0110 affected7 at risk
EG0120 affected8 at risk
EG0130 affected7 at risk
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Confidentiality clauses are in place through a Master Services agreement, which limits the discloser of confidential information to what's expressed in 33.2 and 33.3: disclosure to third party only after written consent, or disclosure of confidential information only to the extent necessary to comply with reporting obligations from AZ, CRO or applicable laws.