Clinical trial NCT01404234: Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Pseudomonas Aeruginosa
Keywords: Cystic fibrosis
CF
PA
Pseudomonas aeruginosa
AZLI
aztreonam
Chronic Pseudomonas aeruginosa
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-07-28
Enrollment: 61
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons
timeFrame: Baseline to Day 168
Secondary outcomes:
measure: Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years
timeFrame: Baseline to Day 28, 84, and 140
measure: Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years
timeFrame: Baseline to Day 28, 84, and 140
measure: Change in Pseudomonas Aeruginosa (PA) Sputum Density
timeFrame: Baseline to Day 28, 84, and 140
measure: Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics
timeFrame: Baseline to Day 168
measure: Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event
timeFrame: Baseline to Day 168
measure: Number of Days Participants Were Hospitalized Due to a Respiratory Event
timeFrame: Baseline to Day 168
measure: Percentage of Participants With Pulmonary Exacerbations
timeFrame: Baseline to Day 168
measure: Time to Pulmonary Exacerbation
timeFrame: Baseline to Day 168
measure: Percentage of Participants With Study-drug Induced Bronchospasm
timeFrame: Pretreatment at Baseline to 30 minutes following treatment
measure: Adverse Event Rates Adjusted for Study Duration
timeFrame: Baseline to Day 168
Other outcomes:
Locations:
city: Aurora
country: United States
facility: The Children's Hospital - Denver
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital & Clinics
state: Missouri
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Bordeaux
country: France
facility: C.H.U de Bordeaux
city: Lisieux
country: France
facility: Centre Hospitalier Robert Bissons
city: Paris Cedex 15
country: France
facility: Hopital Necker Enfants Malades
city: Berlin
country: Germany
facility: Charite Campus Virchow Klinikum
city: Bochum
country: Germany
facility: Universitatsklinik St. Josef-Hospital
city: Erlandgen
country: Germany
facility: Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: J.W. Goethe University Hopsital
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria - Policlinico di Catania
city: Florence
country: Italy
facility: A. Meyer Children Hospital Florence
city: Verona
country: Italy
facility: Azienda Ospedaliera Instituti Ospitalieri di Verona
city: Gdansk
country: Poland
facility: Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem
city: Rabka Zdroj
country: Poland
facility: Instytut Gruzlicy I Chorob Pluc
city: Warszawa
country: Poland
facility: Instytut Matki i Dziecka
city: Barcelona
country: Spain
facility: Pediatric Pneunmonology and Cystic Fibrosis Clinic
city: Madrid
country: Spain
facility: Hospital Infantil La Paz
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Malaga
country: Spain
facility: Hosp. Mat-Inf. Carlos Haya
Study officials:
affiliation: Gilead Sciences
name: Mark Bresnik, M.D.
role: STUDY_DIRECTOR
References: