Clinical trial NCT01375049: Aztreonam Lysine for Pseudomonas Infection Eradication Study
Official title: Open-Label Phase 2 Trial to Evaluate the Safety and Efficacy of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Pediatric Patients With Cystic Fibrosis (CF) and New Onset Lower Respiratory Tract Culture Positive for Pseudomonas Aeruginosa (PA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic fibrosis
CF
PA
Pseudomonas aeruginosa
AZLI
aztreonam
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-06-17
Enrollment: 105
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multi-center study in pediatric patients age 3 months to less than 18 years with cystic fibrosis (CF) and newly detected Pseudomonas aeruginosa (PA) pulmonary colonization/infection. All eligible participants will be treated with a 28-day course of Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily. After completion of study drug, subjects will be followed up through Day 196 for safety and recurrence of PA.

The primary objective is to evaluate the proportion of participants with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing AZLI treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).


Eligibility criteria: Inclusion Criteria:

* Males or females age 3 months to less than 18 years
* 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 test OR
* Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND
* One or more clinical features consistent with CF
* Documented new onset of positive lower respiratory tract culture (e.g., throat swab, sputum, or BAL) for PA within 30 days of study entry (prior to screening visit) defined as either first lifetime documented PA-positive culture OR PA recovered after at least a 2 year history of PA-negative respiratory cultures (at least 2 cultures per year)
* Forced expiratory volume in 1 second (FEV1) ≥ 80% predicted at screening visit (subjects ≥ 6 years of age)
* 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.
* All sexually active females who were of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study. Females utilizing hormonal contraceptives as a birth control method must have used the same method for at least 3 months prior to study drug dosing.
* Males must agree to use barrier contraception (condom with spermicide) during heterosexual intercourse from screening through to study completion and for 90 days from the last dose of study investigational medicinal product
* Participants and/or parent/guardian must be able to give written informed consent prior to any study related procedure

Exclusion Criteria:

* Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit)
* Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit)
* History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
* History of local or systemic hypersensitivity to monobactam antibiotics
* History of intolerance to inhaled short acting beta 2 agonists
* History of lung transplantation
* History of AZLI (or Cayston®) administration
* Administration of any investigational drug or device within 28 days prior to screening visit or within 6 half-lives of the investigational drug (whichever is longer)
* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
* Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
* 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 antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening visit; for participants on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline is allowed
* 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 12 months, defined as:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times upper limit of normal (ULN), or
* Serum creatinine \> 2 times ULN for age
* Pregnant or lactating females; a negative urine pregnancy test is required for all females of childbearing potential (unless surgically sterile), and confirmatory serum pregnancy test in the event of an initial positive urine test result
* Any serious or active medical or psychiatric illness (including drug or alcohol abuse), which in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol
* Presence of a condition or abnormality that would compromise the patient's safety or the quality of study data, in the opinion of the investigator

Primary outcomes:
measure: Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set)
timeFrame: Day 28 to Day 196
measure: Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set)
timeFrame: Day 28 to Day 196
Secondary outcomes:
measure: Change From Baseline in FEV1% Predicted
timeFrame: Baseline to Days 28, 56, 112, and 196
measure: Change From Baseline in CFQ-R RSS Score
timeFrame: Baseline to Days 28, 56, 112, and 196
measure: Percentage of Participants With PA-negative Cultures
timeFrame: Days 28, 56, 112, and 196
measure: Use of Additional (Non-study) Antipseudomonal Antibiotics
timeFrame: Baseline to Day 196
measure: Change From Baseline in Weight
timeFrame: Baseline to Days 28, 56, 112, and 196
measure: Change From Baseline in Height
timeFrame: Baseline to Days 28, 56, 112, and 196
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline to Days 28, 56, 112, and 196
measure: Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam
timeFrame: Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Jacksonville
country: United States
facility: Nemours Children's Clinic- Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Childrens Clinic Orlando
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: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Missouri
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Great Neck
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Children's Hospital CF Research Center
state: Ohio
city: Hershey
country: United States
facility: PennState Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
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: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck Abt. für Kinder- und Jugendheilkunde, Pädiatrie III (Zystische Fibrose)
city: Brussels
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola Brussels
city: Brussels
country: Belgium
facility: Paediatrics, University Hospital Brussels (UZB)
city: Ghent
country: Belgium
facility: Pediatric Respiratory Department, Ghent University Hospital
city: Leuven
country: Belgium
facility: Pediatric Pulmonology, Dept Pediatrics University Hospital Gasthuisberg
city: Bordeaux
country: France
facility: CHU de Boredaux Hôpital des Enfants - Pellegrin CEDRE
city: Clermont Ferrand
country: France
facility: CRCM mixte / CHU ESTAING
city: Creteil
country: France
facility: CHI de Créteil Departement pediatrie
city: Lisieux
country: France
facility: Centre hospitalier Robert Bissons CRCM - service pédiatrie
city: Paris
country: France
facility: Service pédiatrie II Hôpital Necker Enfants Malades
city: Paris
country: France
facility: Hopital Robert Debre
city: Roscoff
country: France
facility: Centre de Ressources et de Compétences sur la Mucoviscidose ( CRCM), Roscoff, France
city: Berlin
country: Germany
facility: Charité Campus Virchow Klinikum, Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunolgie Prof. Wahn
city: Bochum
country: Germany
facility: Klinik fur Kinder- und Jugendmedizinim St Josef-Hopsital
city: Erlangen
country: Germany
facility: Universitätsklinikum Essen, Zentrum für Kinderheilkunde - Abteilung Allg. Kinderheilkunde/Neuropaediatrie
city: Essen
country: Germany
facility: Universitaetsklinikum Bonn-Zentrum fuer Kinderheikunde
city: Frankfurt
country: Germany
facility: Christiane Herzog CF-Center, Goethe University Hospital
city: Giessen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Tubingen
country: Germany
facility: University Children's Hospital
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria di Catania, Dipartimento di Pediatria, UO Broncopneumologia Pediatrica
city: Florence
country: Italy
facility: Cystic Fibrosis Centre Paediatric Department, A. Meyer Children Hospital Florence
city: Napoli
country: Italy
facility: Universita' Federico II di Napoli
city: Rome
country: Italy
facility: Fondazione IRCCS, Ospedale Pediatrico, Bambino Gesu' di Roma
city: Verona
country: Italy
facility: Centro Fibrosi Cistica di Verona, Azienda Ospedaliera Universitaria Integrata di Verona
city: Rotterdam
country: Netherlands
facility: Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
city: Utrecht
country: Netherlands
facility: Longziekten Universitair Medisch (PEDIATRIC), Ultrecht
city: Bialystok
country: Poland
facility: ISPL Centrum Medyczne
city: Gdansk
country: Poland
facility: Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem, Poradnia Leczenia Mukowiscydozy
city: Rabka Zdroj
country: Poland
facility: Instytut Gruźlicy i Chorób Płuc, Klinki Pneumologii i Mukowiscydozy
city: Warszawa
country: Poland
facility: Instytut Matki i Dziecka Klinika Pediatrii
city: Barcelona
country: Spain
facility: Hospital Vall D' Hebron Pediatric Pneunmonology and Cystic Fibrosis Clinic
city: Madrid
country: Spain
facility: Hospital infantil Universitario Niño Jesus, Servicio de Neumología Pediatrica
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Infantil La Paz
city: Malaga
country: Spain
facility: Hospital Materno-Infantil Carlos Haya, Servicio de Neumología Pediatrica
Study officials:
affiliation: Gilead Sciences
name: Mark Bresnik, MD
role: STUDY_DIRECTOR
References:
citation: Tiddens HA, De Boeck K, Clancy JP, Fayon M, H G M A, Bresnik M, Derchak A, Lewis SA, Oermann CM; ALPINE study investigators. Open label study of inhaled aztreonam for Pseudomonas eradication in children with cystic fibrosis: The ALPINE study. J Cyst Fibros. 2015 Jan;14(1):111-9. doi: 10.1016/j.jcf.2014.06.003. Epub 2014 Aug 1.