Cystic FibrosisPhase 3NCT01059565
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection
A Phase 3 study testing AZLI in people with Cystic Fibrosis and Burkholderia Infections, run by Gilead Sciences at 35 sites in 2 countries.
Trial summary
The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis, Burkholderia Infections
- What is being tested?
- AZLI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 35 sitesin 2 countries
- Study dates
- Feb 2010to Jan 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female ≥ 6 years of age
- Subjects with CF as diagnosed by one of the following:
- Documented sweat chloride ≥ 60 milliequivalent (mEq)/L by quantitative pilocarpine iontophoresis test
- Documented sweat sodium ≥ 60 mmol/L
- Two well-characterized genetic mutations in the CF transmembrane conductance regulator (CFTR) gene
- Abnormal nasal potential difference (NPD) with accompanying symptoms characteristic of CF
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- Chronic infection with Burkholderia spp. defined by:
- One sputum (or bronchoalveolar lavage) culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
- At least 50% of sputum (or bronchoalveolar lavage) cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
- At least one positive sputum (or bronchoalveolar lavage) culture (obtained at any point in time) confirmed to be Burkholderia spp. by the Cystic Fibrosis Foundation (CFF) Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory).
- Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment were eligible, but must have been at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment were eligible without restriction on their aerosolized antibiotic treatment.
- Chest radiograph, computed tomography (CT), or magnetic resonance imaging (MRI) (most recent, obtained within 90 days of screening) without significant acute findings (eg, infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) were allowed.
- Subjects (and parent/guardian as required) must have been able to provide written informed consent/assent prior to any study-related procedures,
- Ability to perform reproducible pulmonary function tests
- Sexually active females of childbearing potential must have agreed to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control was defined as a method that would result in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner.
Who cannot join
- Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
- Administration of AZLI treatment within the 28 days prior to randomization/baseline
- Known local or systemic hypersensitivity to monobactam antibiotics
- History of lung transplantation
- Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of the normal range (ULN)
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- Serum creatinine > 2 times ULN
- Known portal hypertension or complications of CF hepatopathy
- Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential were tested
- Any female of childbearing potential who was lactating or not practicing a highly effective method of birth control as defined in the protocol
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would have interfered with subject treatment, assessment or compliance with the protocol
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States34 sites
Study site
Akron, Ohio, 44308
Study site
Albuquerque, New Mexico, 87131
Study site
Boston, Massachusetts, 02115
Study site
Chapel Hill, North Carolina, 27599
Study site
Charleston, South Carolina, 29425
Study site
Columbia, South Carolina, 29203
Study site
Columbus, Ohio, 43205
Study site
Denver, Colorado, 80206
Study site
Detroit, Michigan, 48201
Study site
Glenview, Illinois, 60025
Study site
Hartford, Connecticut, 06102
Study site
Hershey, Pennsylvania, 17033
Study site
Jacksonville, Florida, 32207
Study site
Las Vegas, Nevada, 89107
Study site
Little Rock, Arkansas, 72205
Study site
Miami, Florida, 33136
Study site
Milwaukee, Wisconsin, 53201
Study site
Minneapolis, Minnesota, 55455
Study site
Mobile, Alabama, 36608
Study site
Morgantown, West Virginia, 26506
Study site
Morristown, New Jersey, 07962
Study site
New Brunswick, New Jersey, 08903
Study site
New Hyde Park, New York, 11040
Study site
Oklahoma City, Oklahoma, 73112
Study site
Philadelphia, Pennsylvania, 19104
Study site
Phoenix, Arizona, 85016
Study site
Pittsburgh, Pennsylvania, 15201
Study site
Portland, Oregon, 97239
Study site
Richmond, Virginia, 23298
Study site
St Louis, Missouri, 63110
Study site
Tampa, Florida, 33606
Study site
Toledo, Ohio, 43606
Study site
Wilmington, Delaware, 19803
Study site
Worcester, Massachusetts, 01605
About this study
Official title: Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trial to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis (CF) and Chronic Burkholderia Species Infection
The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF).
Spirometry was used to assess pulmonary function, and the revised Cystic Fibrosis Questionnaire (CFQ-R) was used to assess quality of life. The CFQ-R is a validated, patient-reported outcome tool used to measure health-related quality of life for children and adults with CF.
The study consisted of a 24-week randomized phase, and a 24-week open-label phase. Primary and secondary efficacy analyses were conducted for the 24-week randomized phase only. Safety data were collected for both the randomized and open-label phases.
- Conditions
- Cystic Fibrosis, Burkholderia Infections
- Being tested
- AZLI, Placebo
- Keywords
- Cystic Fibrosis, Aztreonam Lysine, lung infection, Burkholderia, CFQ-R, inhaled antibiotic
- Medical subject headings
- Cystic Fibrosis, Burkholderia Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZLIDrug
Aztreonam for inhalation solution (AZLI; 75 mg aztreonam/52.5 mg lysine monohydrate) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer.
PlaceboDrug
Placebo to match AZLI (lactose and sodium chloride) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer.
| Study group | Role | What they receive |
|---|---|---|
| AZLI | Experimental | Participants were randomized to receive AZLI for up to 24 weeks and may have continued to receive AZLI during the open-label phase for up to an additional 24 weeks. Receives: Drug: AZLI |
| Placebo | Placebo comparator | Participants were randomized to receive placebo to match AZLI for up to 24 weeks and may have switched to AZLI during the open-label phase for up to 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24
The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. 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. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.
Measured: Baseline to Week 24
Secondary outcomes (13)
Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events
The total number of systemic and/or inhaled antibiotic courses for respiratory events from baseline to Week 24 was analyzed. A single antibiotic course may represent the use of multiple antibiotics.
Measured: Baseline to Week 24
AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24
The change (AUCave) in CFQ-R RSS scores from baseline to Week 24 was analyzed.
The range of scores (units) within the RSS domain is 0 to 100 with higher scores indicating fewer symptoms.
Measured: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FEV1
The relative change (AUCave) from baseline to Week 24 in mean (SE) FEV1 was analyzed. FEV1 is defined as the maximal volume of air that can be exhaled in 1 second.
Measured: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FVC
The relative change (AUCave) from baseline to Week 24 in mean (SE) FVC was analyzed. FVC is defined as the volume of air that can forcibly be blown out after taking a full breath.
Measured: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FEF25-75
The relative change (AUCave) from baseline to Week 24 in mean (SE) FEF25-75 was analyzed. FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC.
Measured: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Physical Functioning Score as Assessed by the CFQ-R
The change (AUCave) from baseline to Week 24 in the physical functioning score as assessed by the CFQ-R was analyzed.
The range of scores (units) in the CFQ-R physical functioning domain is 0 to 100 with higher scores indicating better QOL.
Measured: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Weight Score as Assessed by the CFQ-R
The change (AUCave) from baseline to Week 24 in the weight score as assessed by the CFQ-R was analyzed.
The range of scores (units) in the CFQ-R weight domain is 0 to 100 with higher scores indicating better QOL.
Measured: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Treatment Burden Score as Assessed by the CFQ-R
The change (AUCave) from baseline to Week 24 in the treatment burden score as assessed by the CFQ-R was analyzed.
The range of scores (units) in the CFQ-R treatment burden domain is 0 to 100 with higher scores indicating better QOL.
Measured: Baseline to Week 24
Change in BMI From Baseline to Week 24
The change in BMI from baseline to Week 24 was analyzed.
Measured: Baseline to Week 24
Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24
The change in Burkholderia spp. CFU in sputum from baseline to Week 24 was analyzed.
Measured: Baseline to Week 24
Percentage of Days Participants Used Antibiotics
The percentage of days participants used antibiotics from baseline to Week 24 was analyzed. Antibiotics ongoing at baseline or started on or after first dose date were included in the analysis. A single antibiotic course could represent the use of multiple antibiotics. Days of antibiotic use included unique days.
Measured: Baseline to Week 24
Percent of Days Hospitalized
The percentage of days hospitalized from baseline to Week 24 was analyzed.
Measured: Baseline to Week 24
Percentage of Missed School or Work Days
The percentage of days participants missed school or work from baseline to Week 24 was analyzed.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionSep 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Bresnik, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01059565
- Sponsor's protocol ID
- GS-US-205-0127
- Status last verified
- Feb 2014
- First submitted
- 28 Jan 2010
- Last updated
- 11 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trial to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis (CF) and Chronic Burkholderia Species Infection
- ClinicalTrials.gov ID
- NCT01059565
- Acronym / sponsor ID
- GS-US-205-0127
- Conditions
- Cystic Fibrosis, Burkholderia Infections
- Keywords
- Cystic Fibrosis, Aztreonam Lysine, lung infection, Burkholderia, CFQ-R, inhaled antibiotic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 1 Feb 2010 (estimated)
- Results
- Posted 11 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF).
Spirometry was used to assess pulmonary function, and the revised Cystic Fibrosis Questionnaire (CFQ-R) was used to assess quality of life. The CFQ-R is a validated, patient-reported outcome tool used to measure health-related quality of life for children and adults with CF.
The study consisted of a 24-week randomized phase, and a 24-week open-label phase. Primary and secondary efficacy analyses were conducted for the 24-week randomized phase only. Safety data were collected for both the randomized and open-label phases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZLI | Experimental | Drug: AZLIParticipants were randomized to receive AZLI for up to 24 weeks and may have continued to receive AZLI during the open-label phase for up to an additional 24 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants were randomized to receive placebo to match AZLI for up to 24 weeks and may have switched to AZLI during the open-label phase for up to 24 weeks. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Male or female ≥ 6 years of age
- Subjects with CF as diagnosed by one of the following:
- Chronic infection with Burkholderia spp. defined by:
- Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment were eligible, but must have been at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment were eligible without restriction on their aerosolized antibiotic treatment.
- Chest radiograph, computed tomography (CT), or magnetic resonance imaging (MRI) (most recent, obtained within 90 days of screening) without significant acute findings (eg, infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) were allowed.
Key exclusion criteria (11 listed)
- Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
- Administration of AZLI treatment within the 28 days prior to randomization/baseline
- Known local or systemic hypersensitivity to monobactam antibiotics
- History of lung transplantation
- Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZLIAztreonam for inhalation solution (AZLI; 75 mg aztreonam/52.5 mg lysine monohydrate) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer. | Drug | AZLI |
| PlaceboPlacebo to match AZLI (lactose and sodium chloride) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer. | Drug | Placebo |
Primary outcome
AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24
Time frame: Baseline to Week 24
The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. 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. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.
13 secondary outcomes
Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events
Time frame: Baseline to Week 24
AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24
Time frame: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FEV1
Time frame: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FVC
Time frame: Baseline to Week 24
AUCave of Relative Change From Baseline to Week 24 in FEF25-75
Time frame: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Physical Functioning Score as Assessed by the CFQ-R
Time frame: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Weight Score as Assessed by the CFQ-R
Time frame: Baseline to Week 24
AUCave of the Change From Baseline to Week 24 in Treatment Burden Score as Assessed by the CFQ-R
Time frame: Baseline to Week 24
Change in BMI From Baseline to Week 24
Time frame: Baseline to Week 24
Change in Burkholderia Spp. CFU in Sputum From Baseline to Week 24
Time frame: Baseline to Week 24
Percentage of Days Participants Used Antibiotics
Time frame: Baseline to Week 24
Percent of Days Hospitalized
Time frame: Baseline to Week 24
Percentage of Missed School or Work Days
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Bresnik, MD study director
Gilead Sciences
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZLI in people with Cystic Fibrosis and Burkholderia Infections, run by Gilead Sciences at 35 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24 (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2014.