Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CF (AZLI CAT)

April 6, 2016 updated by: Gilead Sciences

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy (CAT) Regimen of Inhaled Antibiotics for the Treatment of Chronic Pulmonary Pseudomonas Aeruginosa Infection in Subjects With Cystic Fibrosis

The primary objective of this study is to evaluate the safety and efficacy of a CAT regimen with aztreonam for inhalation solution (AZLI) and tobramycin inhalation solution (TIS) in adult and pediatric subjects with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection. Participants will be enrolled in a 28 day TIS run-in phase, and will be eligible for randomization in the comparative phase if they have not received non-study oral antibiotics for a respiratory event, or IV or inhaled antibiotics for any indication between Visits 2 and 3, have not developed a condition requiring hospitalization or other change in clinical status which, in the opinion of the investigator would preclude their ability to continue in the study, and have demonstrated at least 50% TIS compliance. Participants enrolled in the comparative phase will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI or placebo for 28 days followed by TIS for 28 days.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
107

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital
    • California
      • La Jolla, California, United States, 92093
        • University of California - San Diego
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Oakland, California, United States, 94611
        • Kaiser Permanente Medical Center
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • District of Columbia
      • Washington DC, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Central Florida Pulmonary Group
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Hollywood, Florida, United States, 33021
        • South Broward Hospital dba Memorial Healthcare System
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic - Jacksonville
      • Miami, Florida, United States, 33136
        • University of Miami
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Orlando, Florida, United States, 32801
        • Nemours Children's Clinic - Orlando
      • Pensacola, Florida, United States, 32504
        • Nemour's Children's Clinic
      • St. Petersburg, Florida, United States, 33701
        • All Children's Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30084
        • Emory Cystic Fibrosis Center
      • Augusta, Georgia, United States, 30912
        • Georgia Health
    • Idaho
      • Boise, Idaho, United States, 37012
        • St. Lukes Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Glenview, Illinois, United States, 60025
        • Chicago CF Care Specialists NFP dba Cystic Fibrosis Institure
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Maine
      • Portland, Maine, United States, 38103
        • Maine Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48201
        • Harper University Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health - Helen DeVos Children's Hospital
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • St. Louis, Missouri, United States, 63104
        • St. Louis University - Cardinal Glennon Children's Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89107
        • Children's Lung Specialists
    • New Hampshire
      • Bedford, New Hampshire, United States, 03110
        • Dartmouth Hitchcock Specialty Care Clinic
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Morristown, New Jersey, United States, 07962
        • Morristown Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • UNM Clinical and Translational Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • New Hyde Park, New York, United States, 11042
        • Long Island Jewish Medical Center - Adult CF & Bronchiectasis Center
      • New York, New York, United States, 10032
        • Gunnar Esiason Adult CF and Lung Program
      • Syracuse, New York, United States, 13210
        • SUNY Upstate University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital
      • Cincinnati, Ohio, United States, 45267
        • UC Health - University of Cincinnati
      • Toledo, Ohio, United States, 43606
        • The Toledo Hospital/Toledo Children's Hospital CF Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • OU Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73112
        • Santiago Reyes, MD
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Clinic
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Drexel University College of Medicine
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Children's Hospital
      • Memphis, Tennessee, United States, 28103
        • Children's Foundation Research Institute/UTHSC
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Children's Hospital
    • Texas
      • Austin, Texas, United States, 78723
        • Austin Children's Chest Associates
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Ft. Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • San Antonio, Texas, United States, 78212
        • Alamo Clinical Research Associates
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Vermont
      • Colchester, Vermont, United States, 05446
        • Vermont Lung Center at the University of Vermont
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Norfolk, Virginia, United States, 23510
        • Children's Hospital of The King's Daughters
      • Richmond, Virginia, United States, 23298
        • VCU Children's Hospital
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53201
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed diagnosis of CF
  • Presence of PA in 2 lower respiratory tract cultures in the 12 months prior to screening
  • Forced expiratory volume (FEV)1 ≥ 25 and ≤ 75% predicted
  • History of 1 hospitalization or 1 course of IV antibiotics for an acute respiratory exacerbation in the 12 months prior to screening

Exclusion Criteria:

  • Concurrent use of oral, IV or inhaled antibiotics at enrollment
  • Concurrent hospitalization at enrollment
  • History of local or systemic hypersensitivity to monobactams or aminoglycoside antibiotics or history of aminoglycoside antibiotic associated toxicity

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: AZLI
Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days.
Drug: AZLI
Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Other Names:
  • Cayston®
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Names:
  • TOBI®
Placebo Comparator: Placebo
Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS for 28 days.
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Names:
  • TOBI®
Drug: Placebo to match AZLI
Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
PDEs were characterized by a change or worsening from baseline of 1 or more documented signs or symptoms (decreased exercise tolerance, increased cough, increased sputum or chest congestion, decreased appetite, or other signs or symptoms) associated with the use of non-study IV or inhaled antibiotics and be verified by a blinded independent adjudication committee.
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)
Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20
FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex and body composition. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.
Comparative Phase: Baseline and Weeks 4, 12 and 20
Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs
Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Time to First Protocol-defined Pulmonary Exacerbation
Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Rate of Hospitalizations for a Respiratory Event
Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Average Change From Baseline in the CFQ-R Respiratory Symptom Scale (RSS) Score Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)
Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20
Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS). The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.
Comparative Phase: Baseline and Weeks 4, 12 and 20

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gilead Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Mark Bresnik, MD, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-205-0170
  • 2015-000398-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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