Cystic FibrosisPhase 3PALSNCT01404234
Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways
A Phase 3 study testing AZLI in people with Cystic Fibrosis and Pseudomonas Aeruginosa, run by Gilead Sciences at 29 sites in 6 countries.
Trial summary
This was an open-label, multicenter study in children ≤ 12 years of age with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (PA) infection in the lower airways using three 28-day courses of Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily, each followed by 28 days off AZLI. Read more about this study
- Who is it for?
- Ages Up to 12 years
- Conditions the study is for
- Cystic Fibrosis, Pseudomonas Aeruginosa
- What is being tested?
- AZLI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 29 sitesin 6 countries
- Study dates
- Dec 2011to Apr 2013
- 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 Up to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
- Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
- Abnormal nasal transepithelial potential difference (NPD) test OR
- A genotype with 2 identifiable mutations consistent with CF AND
- One or more clinical features consistent with CF.
- Documented positive lower respiratory tract culture for PA at the screening visit plus two documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (must have been a minimum 3 months apart.)
- Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
Who cannot join
- Use of IV or inhaled antipseudomonal antibiotics within 14 days of study entry
- Presence of a condition or abnormality that would have compromised the participant's safety or the quality of study data, in the opinion of the investigator
- History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
- History of hypersensitivity/adverse reaction to aztreonam
- History of hypersensitivity/adverse reaction to beta-agonists
- History of lung transplantation
Show all 13Show fewer
- Administration of any investigational drug or device within 30 days prior to screening visit or within 6 half-lives of the investigational drug (whichever was longer)
- Hospitalization for pulmonary-related illness within 28 days prior to screening visit
- Changes in or initiation of chronic azithromycin treatment within 28 days prior to screening visit
- Changes in or initiation of hypertonic saline treatment within 7 days prior to screening visit; for subjects on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline was allowed
- Changes in antimicrobial, bronchodilator (BD), corticosteroid or dornase alfa medications within 7 days prior to screening visit;
- Changes in physiotherapy technique or schedule within 7 days prior to screening visit
- Abnormal renal or hepatic function results at most recent test within the previous 90 days
Trial locations and contacts
29 sites in 6 countries.
29 sites in 6 countries
United States10 sites
The Children's Hospital - Denver
Aurora, Colorado, 80045
Children's Hospital Boston
Boston, Massachusetts, 02115
Children's Memorial Hospital
Chicago, Illinois, 60614
Nationwide Children's Hospital
Columbus, Ohio, 43205
Baylor College of Medicine
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospital & Clinics
Kansas City, Missouri, 64108
University of Utah
Salt Lake City, Utah, 84108
SUNY Upstate Medical University
Syracuse, New York, 13210
Germany5 sites
Charite Campus Virchow Klinikum
Berlin
Universitatsklinik St. Josef-Hospital
Bochum
Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde
Erlandgen
Universitatsklinikum Essen
Essen
J.W. Goethe University Hopsital
Frankfurt
Spain5 sites
Pediatric Pneunmonology and Cystic Fibrosis Clinic
Barcelona
Hospital Infantil La Paz
Madrid
Hospital Infantil Universitario Nino Jesus
Madrid
Hospital Ramon y Cajal
Madrid
Hosp. Mat-Inf. Carlos Haya
Málaga
France3 sites
C.H.U de Bordeaux
Bordeaux
Centre Hospitalier Robert Bissons
Lisieux
Hopital Necker Enfants Malades
Paris
Italy3 sites
Azienda Ospedaliero Universitaria - Policlinico di Catania
Catania
A. Meyer Children Hospital Florence
Florence
Azienda Ospedaliera Instituti Ospitalieri di Verona
Verona
Poland3 sites
Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem
Gdansk
Instytut Gruzlicy I Chorob Pluc
Rabka-Zdrój
Instytut Matki i Dziecka
Warsaw
About this study
Official title: Open-Label Phase 3 Trial to Evaluate the Safety of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa (PA) in the Lower Airways
This was an open-label, multicenter study in children ≤ 12 years of age with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (PA) infection in the lower airways using three 28-day courses of Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily, each followed by 28 days off AZLI. The total treatment duration was to be 6 months.
- Conditions
- Cystic Fibrosis, Pseudomonas Aeruginosa
- Being tested
- AZLI
- Keywords
- Cystic fibrosis, CF, PA, Pseudomonas aeruginosa, AZLI, aztreonam, Chronic Pseudomonas aeruginosa
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZLIDrug
Also called Cayston®
AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
| Study group | Role | What they receive |
|---|---|---|
| Open-label AZLI | Experimental | Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. Receives: Drug: AZLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons
Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method.
Measured: Baseline to Day 168
Secondary outcomes (10)
Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years
The change in FEV1 % predicted was assessed at the end of each 28-day AZLI treatment course.
FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition.
Measured: Baseline to Day 28, 84, and 140
Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years
The change in CFQ-R RSS score was assessed at the end of each 28-day AZLI treatment course.
The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms.
Measured: Baseline to Day 28, 84, and 140
Change in Pseudomonas Aeruginosa (PA) Sputum Density
The change in PA sputum density (log10 colony-forming units per gram [cfu/g]) was assessed at the end of each 28-day AZLI treatment course.
Measured: Baseline to Day 28, 84, and 140
Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics
The percentage of participants who used additional (non-study) antipseudomonal antibiotics (IV, inhaled, oral, IV/inhaled, IV/inhaled/oral) was summarized (number and percent) for all subjects.
Measured: Baseline to Day 168
Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event
Measured: Baseline to Day 168
Number of Days Participants Were Hospitalized Due to a Respiratory Event
The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.
Measured: Baseline to Day 168
Percentage of Participants With Pulmonary Exacerbations
Pulmonary exacerbations were defined as respiratory hospitalizations or discrete courses of non-study IV/inhaled antipseudomonal antibiotics. Use of oral antibiotics alone for respiratory signs or symptoms was considered to be representative of milder clinical events and, therefore, was not included in the definition of pulmonary exacerbations.
Measured: Baseline to Day 168
Time to Pulmonary Exacerbation
The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.
Measured: Baseline to Day 168
Percentage of Participants With Study-drug Induced Bronchospasm
Study-drug induced bronchospasm (airway reactivity) was assessed at the baseline visit as the percent change in FEV1 from the pretreatment measurement to 30 minutes following treatment for subjects ≥ 6 years or as from the Investigator's assessment for subjects < 6 years.
Measured: Pretreatment at Baseline to 30 minutes following treatment
Adverse Event Rates Adjusted for Study Duration
Adverse events occurring in ≥ 5% of participants adjusted for study duration were summarized. The adjustment was made by using a standardized rate calculated as the sum of study duration across patients divided by 28 for the total number of patient months. Rate calculations presented are the number of adverse events (AEs) per patient month.
Measured: Baseline to Day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2011 (estimated)
- Study startDec 2011
- Primary completionApr 2013
- Study completionApr 2013
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Bresnik, M.D., Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01404234
- Sponsor's protocol ID
- GS-US-205-0160
- Acronym
- PALS
- Status last verified
- May 2014
- First submitted
- 26 Jul 2011
- Last updated
- 29 May 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 29 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label Phase 3 Trial to Evaluate the Safety of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa (PA) in the Lower Airways
- ClinicalTrials.gov ID
- NCT01404234
- Acronym / sponsor ID
- PALS / GS-US-205-0160
- Conditions
- Cystic Fibrosis, Pseudomonas Aeruginosa
- Keywords
- Cystic fibrosis, CF, PA, Pseudomonas aeruginosa, AZLI, aztreonam, Chronic Pseudomonas aeruginosa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 28 Jul 2011 (estimated)
- Results
- Posted 1 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open-label, multicenter study in children ≤ 12 years of age with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (PA) infection in the lower airways using three 28-day courses of Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily, each followed by 28 days off AZLI. The total treatment duration was to be 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label AZLI | Experimental | Drug: AZLIParticipants received three 28-day courses of AZLI, each followed by 28 days off-treatment. |
Who may qualify
- Ages
- Up to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
- Documented positive lower respiratory tract culture for PA at the screening visit plus two documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (must have been a minimum 3 months apart.)
- Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
Key exclusion criteria (13 listed)
- Use of IV or inhaled antipseudomonal antibiotics within 14 days of study entry
- Presence of a condition or abnormality that would have compromised the participant's safety or the quality of study data, in the opinion of the investigator
- History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
- History of hypersensitivity/adverse reaction to aztreonam
- History of hypersensitivity/adverse reaction to beta-agonists
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 |
|---|---|---|
| AZLIAlso: Cayston®AZLI 75 mg was administered 3 times daily via the investigational nebulizer. | Drug | Open-label AZLI |
Primary outcome
Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons
Time frame: Baseline to Day 168
Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method.
10 secondary outcomes
Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years
Time frame: Baseline to Day 28, 84, and 140
Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years
Time frame: Baseline to Day 28, 84, and 140
Change in Pseudomonas Aeruginosa (PA) Sputum Density
Time frame: Baseline to Day 28, 84, and 140
Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics
Time frame: Baseline to Day 168
Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event
Time frame: Baseline to Day 168
Number of Days Participants Were Hospitalized Due to a Respiratory Event
Time frame: Baseline to Day 168
Percentage of Participants With Pulmonary Exacerbations
Time frame: Baseline to Day 168
Time to Pulmonary Exacerbation
Time frame: Baseline to Day 168
Percentage of Participants With Study-drug Induced Bronchospasm
Time frame: Pretreatment at Baseline to 30 minutes following treatment
Adverse Event Rates Adjusted for Study Duration
Time frame: Baseline to Day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 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, M.D. study director
Gilead Sciences
29 sites in 6 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 Pseudomonas Aeruginosa, run by Gilead Sciences at 29 sites in 6 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 7 inclusion and 13 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 29 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Germany, Spain, France, Italy and 1 more country. 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. 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 1 May 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?
Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons (time frame: Baseline to Day 168). 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 29 May 2014.