Aztreonam Lysine for Pseudomonas Infection Eradication Study

NCT ID: NCT01375049

Last Updated: 2014-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2013-05-31

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).

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aztreonam for Inhalation Solution (AZLI)

Participants will receive one 28-day course of AZLI, then will be followed for a 24-week period (through Day 196).

Group Type: EXPERIMENTAL

Aztreonam for Inhalation Solution (AZLI)

Intervention Type: DRUG

AZLI 75 mg administered 3 times daily via the investigational eFlow® nebulizer

Interventions

Aztreonam for Inhalation Solution (AZLI)

AZLI 75 mg administered 3 times daily via the investigational eFlow® nebulizer

Intervention Type: DRUG

Other Intervention Names

Cayston®

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Bresnik, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Nemours Children's Clinic- Jacksonville

Jacksonville, Florida, United States

Nemours Childrens Clinic Orlando

Orlando, Florida, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Children's Mercy Hospital and Clinics

Kansas City, Missouri, United States

Saint Louis University

St Louis, Missouri, United States

Cohen Children's Medical Center of NY

Great Neck, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Akron Children's Hospital

Akron, Ohio, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Toledo Children's Hospital CF Research Center

Toledo, Ohio, United States

PennState Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Medizinische Universität Innsbruck Abt. für Kinder- und Jugendheilkunde, Pädiatrie III (Zystische Fibrose)

Innsbruck, , Austria

Hôpital Universitaire des Enfants Reine Fabiola Brussels

Brussels, , Belgium

Paediatrics, University Hospital Brussels (UZB)

Brussels, , Belgium

Pediatric Respiratory Department, Ghent University Hospital

Ghent, , Belgium

Pediatric Pulmonology, Dept Pediatrics University Hospital Gasthuisberg

Leuven, , Belgium

CHU de Boredaux Hôpital des Enfants - Pellegrin CEDRE

Bordeaux, , France

CRCM mixte / CHU ESTAING

Clermont-Ferrand, , France

CHI de Créteil Departement pediatrie

Créteil, , France

Centre hospitalier Robert Bissons CRCM - service pédiatrie

Lisieux, , France

Service pédiatrie II Hôpital Necker Enfants Malades

Paris, , France

Hopital Robert Debre

Paris, , France

Centre de Ressources et de Compétences sur la Mucoviscidose ( CRCM), Roscoff, France

Roscoff, , France

Charité Campus Virchow Klinikum, Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunolgie Prof. Wahn

Berlin, , Germany

Klinik fur Kinder- und Jugendmedizinim St Josef-Hopsital

Bochum, , Germany

Universitätsklinikum Essen, Zentrum für Kinderheilkunde - Abteilung Allg. Kinderheilkunde/Neuropaediatrie

Erlangen, , Germany

Universitaetsklinikum Bonn-Zentrum fuer Kinderheikunde

Essen, , Germany

Christiane Herzog CF-Center, Goethe University Hospital

Frankfurt, , Germany

Universitätsklinikum Gießen und Marburg GmbH

Giessen, , Germany

University Children's Hospital

Tübingen, , Germany

Azienda Ospedaliero-Universitaria di Catania, Dipartimento di Pediatria, UO Broncopneumologia Pediatrica

Catania, , Italy

Cystic Fibrosis Centre Paediatric Department, A. Meyer Children Hospital Florence

Florence, , Italy

Universita' Federico II di Napoli

Napoli, , Italy

Fondazione IRCCS, Ospedale Pediatrico, Bambino Gesu' di Roma

Rome, , Italy

Centro Fibrosi Cistica di Verona, Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands

Rotterdam, , Netherlands

Longziekten Universitair Medisch (PEDIATRIC), Ultrecht

Utrecht, , Netherlands

ISPL Centrum Medyczne

Bialystok, , Poland

Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem, Poradnia Leczenia Mukowiscydozy

Gdansk, , Poland

Instytut Gruźlicy i Chorób Płuc, Klinki Pneumologii i Mukowiscydozy

Rabka-Zdrój, , Poland

Instytut Matki i Dziecka Klinika Pediatrii

Warsaw, , Poland

Hospital Vall D' Hebron Pediatric Pneunmonology and Cystic Fibrosis Clinic

Barcelona, , Spain

Hospital infantil Universitario Niño Jesus, Servicio de Neumología Pediatrica

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Infantil La Paz

Madrid, , Spain

Hospital Materno-Infantil Carlos Haya, Servicio de Neumología Pediatrica

Málaga, , Spain

Countries

United States; Austria; Belgium; France; Germany; Italy; Netherlands; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 25091537 (View on PubMed)

Other Identifiers

GS-US-205-0162

Identifier Type: -

Identifier Source: org_study_id