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

NCT01404234 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-205-0160
• Study Type: interventional
• Target: 61
• Locations: 6 countries
• Sites: 29

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.

Conditions

Cystic Fibrosis; Pseudomonas Aeruginosa

Keywords

Cystic fibrosis; CF; PA; Pseudomonas aeruginosa; AZLI; aztreonam; Chronic Pseudomonas aeruginosa

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years

  Baseline to Day 28, 84, and 140

• Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years

  Baseline to Day 28, 84, and 140

• Change in Pseudomonas Aeruginosa (PA) Sputum Density

  Baseline to Day 28, 84, and 140

• Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics

  Baseline to Day 168

• Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event

  Baseline to Day 168

Study Arms (1)

Open-label AZLI

EXPERIMENTAL

Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment.

Drug: AZLI

Interventions

AZLI DRUG

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

Also known as: Cayston®

Open-label AZLI

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (29)

The Children's Hospital - Denver

Aurora, Colorado, 80045, United States

Location

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Children's Mercy Hospital & Clinics

Kansas City, Missouri, 64108, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

C.H.U de Bordeaux

Bordeaux, France

Location

Centre Hospitalier Robert Bissons

Lisieux, France

Location

Hopital Necker Enfants Malades

Paris, France

Location

Charite Campus Virchow Klinikum

Berlin, Germany

Location

Universitatsklinik St. Josef-Hospital

Bochum, Germany

Location

Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde

Erlandgen, Germany

Location

Universitatsklinikum Essen

Essen, Germany

Location

J.W. Goethe University Hopsital

Frankfurt, Germany

Location

Azienda Ospedaliero Universitaria - Policlinico di Catania

Catania, Italy

Location

A. Meyer Children Hospital Florence

Florence, Italy

Location

Azienda Ospedaliera Instituti Ospitalieri di Verona

Verona, Italy

Location

Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem

Gdansk, Poland

Location

Instytut Gruzlicy I Chorob Pluc

Rabka-Zdrój, Poland

Location

Instytut Matki i Dziecka

Warsaw, Poland

Location

Pediatric Pneunmonology and Cystic Fibrosis Clinic

Barcelona, Spain

Location

Hospital Infantil La Paz

Madrid, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hosp. Mat-Inf. Carlos Haya

Málaga, Spain

Location

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Interventions

Aztreonam

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Mark Bresnik, M.D.

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: July 28, 2011
• Study Start: December 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: May 29, 2014
• Results First Posted: May 1, 2014

Record last verified: 2014-05

Locations

DE (5); FR (3); PL (3); US (10); ES (5); IT (3)