Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways
- Registration Number
- NCT01404234
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
-
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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Open-label AZLI AZLI Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons 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
Name Time Method Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event Baseline to Day 168 Adverse Event Rates Adjusted for Study Duration 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.
Percentage of Participants With Pulmonary Exacerbations 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.
Time to Pulmonary Exacerbation Baseline to Day 168 The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.
Percentage of Participants With Study-drug Induced Bronchospasm 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.
Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years 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.Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years 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.Change in Pseudomonas Aeruginosa (PA) Sputum Density 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.
Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics 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.
Number of Days Participants Were Hospitalized Due to a Respiratory Event 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.
Trial Locations
- Locations (29)
Charite Campus Virchow Klinikum
🇩🇪Berlin, Germany
J.W. Goethe University Hopsital
🇩🇪Frankfurt, Germany
Hopital Necker Enfants Malades
🇫🇷Paris Cedex 15, France
Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde
🇩🇪Erlandgen, Germany
Nemours Children's Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Centre Hospitalier Robert Bissons
🇫🇷Lisieux, France
C.H.U de Bordeaux
🇫🇷Bordeaux, France
Hosp. Mat-Inf. Carlos Haya
🇪🇸Malaga, Spain
Children's Mercy Hospital & Clinics
🇺🇸Kansas City, Missouri, United States
Universitatsklinik St. Josef-Hospital
🇩🇪Bochum, Germany
Instytut Gruzlicy I Chorob Pluc
🇵🇱Rabka Zdroj, Poland
Azienda Ospedaliero Universitaria - Policlinico di Catania
🇮🇹Catania, Italy
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem
🇵🇱Gdansk, Poland
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
Instytut Matki i Dziecka
🇵🇱Warszawa, Poland
Universitatsklinikum Essen
🇩🇪Essen, Germany
University of Utah
🇺🇸Salt Lake City, Utah, United States
The Children's Hospital - Denver
🇺🇸Aurora, Colorado, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Hospital Infantil La Paz
🇪🇸Madrid, Spain
A. Meyer Children Hospital Florence
🇮🇹Florence, Italy
Azienda Ospedaliera Instituti Ospitalieri di Verona
🇮🇹Verona, Italy
Pediatric Pneunmonology and Cystic Fibrosis Clinic
🇪🇸Barcelona, Spain