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).
Minimum age: 3 Months.
Maximum age: 17 Years.
Gender(s): Both.
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
Medizinische Universität Innsbruck Abt. für Kinder- und Jugendheilkunde, Pädiatrie III (Zystische Fibrose), Innsbruck 6020, Austria
Hôpital Universitaire des Enfants Reine Fabiola Brussels, Brussels 1020, Belgium
Paediatrics, University Hospital Brussels (UZB), Brussels 1090, Belgium
Pediatric Respiratory Department, Ghent University Hospital, Ghent 9000, Belgium
Pediatric Pulmonology, Dept Pediatrics University Hospital Gasthuisberg, Leuven 3000, Belgium
CHU de Boredaux Hôpital des Enfants - Pellegrin CEDRE, Bordeaux 33076, France
CRCM mixte / CHU ESTAING, Clermont Ferrand 63003, France
CHI de Créteil Departement pediatrie, Creteil 94000, France
Centre hospitalier Robert Bissons CRCM - service pédiatrie, Lisieux 14100, France
Hopital Robert Debre, Paris, France
Service pédiatrie II Hôpital Necker Enfants Malades, Paris 75743, France
Centre de Ressources et de Compétences sur la Mucoviscidose ( CRCM), Roscoff, France, Roscoff 29684, France
Charité Campus Virchow Klinikum, Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunolgie Prof. Wahn, Berlin 13353, Germany
Klinik fur Kinder- und Jugendmedizinim St Josef-Hopsital, Bochum, Germany
Universitätsklinikum Essen, Zentrum für Kinderheilkunde - Abteilung Allg. Kinderheilkunde/Neuropaediatrie, Erlangen 91054, Germany
Universitaetsklinikum Bonn-Zentrum fuer Kinderheikunde, Essen, Germany
Christiane Herzog CF-Center, Goethe University Hospital, Frankfurt 60590, Germany
Universitätsklinikum Gießen und Marburg GmbH, Giessen 35392, Germany
University Children's Hospital, Tubingen 72076, Germany
Azienda Ospedaliero-Universitaria di Catania, Dipartimento di Pediatria, UO Broncopneumologia Pediatrica, Catania 95123, Italy
Cystic Fibrosis Centre Paediatric Department, A. Meyer Children Hospital Florence, Florence 50139, Italy
Universita' Federico II di Napoli, Napoli 80131, Italy
Fondazione IRCCS, Ospedale Pediatrico, Bambino Gesu' di Roma, Rome 00165, Italy
Centro Fibrosi Cistica di Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona 37126, Italy
Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands, Rotterdam 3015 GJ, Netherlands
Longziekten Universitair Medisch (PEDIATRIC), Ultrecht, Utrecht 3584 EA, Netherlands
ISPL Centrum Medyczne, Bialystok 15-003, Poland
Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem, Poradnia Leczenia Mukowiscydozy, Gdansk 80-308, Poland
Instytut Gruźlicy i Chorób Płuc, Klinki Pneumologii i Mukowiscydozy, Rabka Zdroj 34-700, Poland
Instytut Matki i Dziecka Klinika Pediatrii, Warszawa 01-211, Poland
Hospital Vall D' Hebron Pediatric Pneunmonology and Cystic Fibrosis Clinic, Barcelona 08035, Spain
Hospital Infantil La Paz, Madrid, Spain
Hospital infantil Universitario Niño Jesus, Servicio de Neumología Pediatrica, Madrid 28009, Spain
Hospital Ramon y Cajal, Madrid 28049, Spain
Hospital Materno-Infantil Carlos Haya, Servicio de Neumología Pediatrica, Malaga 29011, Spain
Phoenix Children's Hospital, Phoenix, Arizona 85016, United States
Nemours Children's Clinic- Jacksonville, Jacksonville, Florida 32207, United States
Nemours Childrens Clinic Orlando, Orlando, Florida 32801, United States
Children's Memorial Hospital, Chicago, Illinois 60614, United States
Riley Hospital for Children, Indianapolis, Indiana 46202, United States
Children's Hospital Boston, Boston, Massachusetts 02115, United States
University of Michigan, Ann Arbor, Michigan 48109, United States
Children's Mercy Hospital and Clinics, Kansas City, Missouri 64108, United States
Saint Louis University, St. Louis, Missouri 63104, United States
Cohen Children's Medical Center of NY, Great Neck, New York 11021, United States
SUNY Upstate Medical University, Syracuse, New York 13210, United States
UNC Chapel Hill, Chapel Hill, North Carolina 27599, United States
Akron Children's Hospital, Akron, Ohio 44308, United States
Cincinnati Children's Hospital, Cincinnati, Ohio 45229, United States
Nationwide Children's Hospital, Columbus, Ohio 43205, United States
Toledo Children's Hospital CF Research Center, Toledo, Ohio 43606, United States
PennState Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, United States
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, United States
Vanderbilt Children's Hospital, Nashville, Tennessee 37232, United States
Baylor College of Medicine, Houston, Texas 77030, United States
University of Utah, Salt Lake City, Utah 84108, United States
Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53201, United States