Back to resultsTo Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)
Primary Purpose
Complicated Infection, Bacterial Infections
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Avibactam (AVI)
Aztreonam (ATM)
combination of Aztreonam - Avibactam (ATM-AVI)
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Complicated Infection focused on measuring Phase I, Safety, tolerability, healthy.
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
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Drug: A
Drug: B
Drug: C
Drug: D
Arm Description
Avibactam (AVI)
Aztreonam (ATM)
combination of Aztreonam-Avibactam (ATM-AVI)
Matching Placebo
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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)
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.
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01689207
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Infection, Bacterial Infections
Keywords
Phase I, Safety, tolerability, healthy.
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
222 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Drug: A
Arm Type
Experimental
Arm Description
Avibactam (AVI)
Arm Title
Drug: B
Arm Type
Experimental
Arm Description
Aztreonam (ATM)
Arm Title
Drug: C
Arm Type
Experimental
Arm Description
combination of Aztreonam-Avibactam (ATM-AVI)
Arm Title
Drug: D
Arm Type
Placebo Comparator
Arm Description
Matching Placebo
Intervention Type
Drug
Intervention Name(s)
Avibactam (AVI)
Intervention Description
PART A: AVI IV infusion
Intervention Type
Drug
Intervention Name(s)
Aztreonam (ATM)
Intervention Description
PART A: ATM IV infusion
Intervention Type
Drug
Intervention Name(s)
combination of Aztreonam - Avibactam (ATM-AVI)
Intervention Description
PART A: ATM-AVI IV infusion. PART B and C: ATM-AVI IV infusions.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
PART A, PART B, PART C: matching placebo IV infusions
Primary Outcome Measure Information:
Title
Safety Profile - Number of Subjects With at Least 1 AE
Description
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.
Time Frame
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 Outcome Measure Information:
Title
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
Description
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).
Time Frame
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
Title
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
Description
Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.
Time Frame
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
Title
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
Description
Time to Cmax (tmax)
Time Frame
Day 1
Title
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Description
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.
Time Frame
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
Title
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
Description
Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.
Time Frame
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
Title
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
Description
Volume of distribution at steady state (Vss).
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frans van den Berg, MD
Organizational Affiliation
Hammersmith Medicines Research Cumberland Avenue Park Royal London NW10 7EW, England Telephone: +44 020 8961 4130 Fax: +44 020 8961 8665
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)
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