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Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways (PALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01404234
Recruitment Status : Completed
First Posted : July 28, 2011
Results First Posted : May 1, 2014
Last Update Posted : May 29, 2014
Information provided by (Responsible Party):
Gilead Sciences

Brief 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. The total treatment duration was to be 6 months.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Pseudomonas Aeruginosa Drug: AZLI Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : December 2011
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 2013

Arm Intervention/treatment
Experimental: Open-label AZLI
Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment.
Drug: AZLI
AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Other Name: Cayston®

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years [ Time Frame: Baseline to Day 28, 84, and 140 ]

    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.

  2. 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 ]

    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.

  3. Change in Pseudomonas Aeruginosa (PA) Sputum Density [ Time Frame: Baseline to Day 28, 84, and 140 ]
    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.

  4. Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics [ Time Frame: Baseline to Day 168 ]
    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.

  5. Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event [ Time Frame: Baseline to Day 168 ]
  6. Number of Days Participants Were Hospitalized Due to a Respiratory Event [ Time Frame: Baseline to Day 168 ]
    The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.

  7. Percentage of Participants With Pulmonary Exacerbations [ Time Frame: Baseline to Day 168 ]
    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.

  8. Time to Pulmonary Exacerbation [ Time Frame: Baseline to Day 168 ]
    The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.

  9. Percentage of Participants With Study-drug Induced Bronchospasm [ Time Frame: Pretreatment at Baseline to 30 minutes following treatment ]
    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.

  10. Adverse Event Rates Adjusted for Study Duration [ Time Frame: Baseline to Day 168 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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

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 identifier (NCT number): NCT01404234

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Sponsors and Collaborators
Gilead Sciences
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Study Director: Mark Bresnik, M.D. Gilead Sciences
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Responsible Party: Gilead Sciences Identifier: NCT01404234    
Other Study ID Numbers: GS-US-205-0160
First Posted: July 28, 2011    Key Record Dates
Results First Posted: May 1, 2014
Last Update Posted: May 29, 2014
Last Verified: May 2014
Keywords provided by Gilead Sciences:
Cystic fibrosis
Pseudomonas aeruginosa
Chronic Pseudomonas aeruginosa
Additional relevant MeSH terms:
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Cystic Fibrosis
Pseudomonas Infections
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses