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

Cystic Fibrosis Clinical Trial

— PALS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01404234
• Other study ID #: GS-US-205-0160
• Status: Completed
• Phase: Phase 3
• First received: July 26, 2011
• Last updated: May 12, 2014
• Start date: December 2011
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Ethics CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesFrance: Ministry of HealthSpain: Comité Ético de Investigación ClínicaItaly: Ministry of Health
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 12 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pseudomonas Aeruginosa
• Pseudomonas Infections

Intervention

Drug:
• AZLI
AZLI 75 mg was administered 3 times daily via the investigational nebulizer.

Locations

Country	Name	City	State
France	C.H.U de Bordeaux	Bordeaux
France	Centre Hospitalier Robert Bissons	Lisieux
France	Hopital Necker Enfants Malades	Paris Cedex 15
Germany	Charite Campus Virchow Klinikum	Berlin
Germany	Universitatsklinik St. Josef-Hospital	Bochum
Germany	Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde	Erlandgen
Germany	Universitatsklinikum Essen	Essen
Germany	J.W. Goethe University Hopsital	Frankfurt
Italy	Azienda Ospedaliero Universitaria - Policlinico di Catania	Catania
Italy	A. Meyer Children Hospital Florence	Florence
Italy	Azienda Ospedaliera Instituti Ospitalieri di Verona	Verona
Poland	Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem	Gdansk
Poland	Instytut Gruzlicy I Chorob Pluc	Rabka Zdroj
Poland	Instytut Matki i Dziecka	Warszawa
Spain	Pediatric Pneunmonology and Cystic Fibrosis Clinic	Barcelona
Spain	Hospital Infantil La Paz	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hosp. Mat-Inf. Carlos Haya	Malaga
United States	The Children's Hospital - Denver	Aurora	Colorado
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	Children's Mercy Hospital & Clinics	Kansas City	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Day 168	No
Secondary	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.	Baseline to Day 28, 84, and 140	No
Secondary	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.	Baseline to Day 28, 84, and 140	No
Secondary	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.	Baseline to Day 28, 84, and 140	No
Secondary	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.	Baseline to Day 168	No
Secondary	Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event		Baseline to Day 168	No
Secondary	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.	Baseline to Day 168	No
Secondary	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.	Baseline to Day 168	No
Secondary	Time to Pulmonary Exacerbation	The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.	Baseline to Day 168	No
Secondary	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.	Pretreatment at Baseline to 30 minutes following treatment	Yes
Secondary	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.	Baseline to Day 168	No