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To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)

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ClinicalTrials.gov Identifier: NCT01689207
Recruitment Status : Completed
First Posted : September 21, 2012
Results First Posted : October 26, 2016
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Complicated Infection Bacterial Infections Drug: Avibactam (AVI) Drug: Aztreonam (ATM) Drug: combination of Aztreonam - Avibactam (ATM-AVI) Drug: Placebo Phase 1

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)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 222 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
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 Start Date : September 2012
Primary Completion Date : December 2014
Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Aztreonam
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Drug: A
Avibactam (AVI)
Drug: Avibactam (AVI)
PART A: AVI IV infusion
Experimental: Drug: B
Aztreonam (ATM)
Drug: Aztreonam (ATM)
PART A: ATM IV infusion
Experimental: Drug: C
combination of Aztreonam-Avibactam (ATM-AVI)
Drug: combination of Aztreonam - Avibactam (ATM-AVI)
PART A: ATM-AVI IV infusion. PART B and C: ATM-AVI IV infusions.
Placebo Comparator: Drug: D
Matching Placebo
Drug: Placebo
PART A, PART B, PART C: matching placebo IV infusions



Primary Outcome Measures :
  1. Safety Profile - Number of Subjects With at Least 1 AE [ 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) ]
    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 :
  1. 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 [ 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 ]
    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).

  2. 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 [ 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 ]
    Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.

  3. 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 Frame: Day 1 ]
    Time to Cmax (tmax)

  4. PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C [ 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 ]
    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.

  5. 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 [ 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 ]
    Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.

  6. PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C [ 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 ]
    Volume of distribution at steady state (Vss).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01689207


Locations
United Kingdom
Research Site
London, United Kingdom
Sponsors and Collaborators
Pfizer
Investigators
Principal Investigator: 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

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01689207     History of Changes
Other Study ID Numbers: D4910C00001
First Posted: September 21, 2012    Key Record Dates
Results First Posted: October 26, 2016
Last Update Posted: September 6, 2017
Last Verified: August 2017

Keywords provided by Pfizer:
Phase I, Safety, tolerability, healthy.

Additional relevant MeSH terms:
Infection
Communicable Diseases
Bacterial Infections
Aztreonam
Avibactam
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action