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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01404234
First received: July 26, 2011
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Cystic Fibrosis
Pseudomonas Aeruginosa
Drug: AZLI
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years [ Time Frame: Baseline to Day 28, 84, and 140 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • Change in Pseudomonas Aeruginosa (PA) Sputum Density [ Time Frame: Baseline to Day 28, 84, and 140 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
  • Number of Days Participants Were Hospitalized Due to a Respiratory Event [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.

  • Percentage of Participants With Pulmonary Exacerbations [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    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.

  • Time to Pulmonary Exacerbation [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.

  • Percentage of Participants With Study-drug Induced Bronchospasm [ Time Frame: Pretreatment at Baseline to 30 minutes following treatment ] [ Designated as safety issue: Yes ]
    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.

  • Adverse Event Rates Adjusted for Study Duration [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    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.


Enrollment: 61
Study Start Date: December 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

  Eligibility

Ages Eligible for Study:   up to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01404234

  Show 29 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Mark Bresnik, M.D. Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01404234     History of Changes
Other Study ID Numbers: GS-US-205-0160
Study First Received: July 26, 2011
Results First Received: March 31, 2014
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Ethics Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
France: Ministry of Health
Spain: Comité Ético de Investigación Clínica
Italy: Ministry of Health

Keywords provided by Gilead Sciences:
Cystic fibrosis
CF
PA
Pseudomonas aeruginosa
AZLI
aztreonam
Chronic Pseudomonas aeruginosa

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pseudomonas Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Gram-Negative Bacterial Infections
Bacterial Infections
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014