Aztreonam Lysine for Pseudomonas Infection Eradication Study

Cystic Fibrosis Clinical Trial

— ALPINE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01375049
• Other study ID #: GS-US-205-0162
• Status: Completed
• Phase: Phase 2
• First received: June 15, 2011
• Last updated: July 7, 2014
• Start date: August 2011
• Est. completion date: May 2013

Study information

• Verified date: July 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicines and Health Products, FAMHPGermany: Federal Institute for Drugs and Medical DevicesFrance: National Agency for the Safety of Medicine and Health ProductsSpain: Spanish Agency of MedicinesItaly: The Italian Medicines AgencyAustria: Agency for Health and Food SafetyNetherlands: Medicines Evaluation Board (MEB)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 17 Years

Eligibility

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

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 Infections

Intervention

Drug:
• Aztreonam for Inhalation Solution (AZLI)
AZLI 75 mg administered 3 times daily via the investigational eFlow® nebulizer

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck Abt. für Kinder- und Jugendheilkunde, Pädiatrie III (Zystische Fibrose)	Innsbruck
Belgium	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
France	CHU de Boredaux Hôpital des Enfants - Pellegrin CEDRE	Bordeaux
France	CRCM mixte / CHU ESTAING	Clermont Ferrand
France	CHI de Créteil Departement pediatrie	Creteil
France	Centre hospitalier Robert Bissons CRCM - service pédiatrie	Lisieux
France	Hopital Robert Debre	Paris
France	Service pédiatrie II Hôpital Necker Enfants Malades	Paris
France	Centre de Ressources et de Compétences sur la Mucoviscidose ( CRCM), Roscoff, France	Roscoff
Germany	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	Tubingen
Italy	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
Netherlands	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
Poland	ISPL Centrum Medyczne	Bialystok
Poland	Specjalistyczny Zespól Opieki Zdrowotnej nad Matka i Dzieckiem, Poradnia Leczenia Mukowiscydozy	Gdansk
Poland	Instytut Gruzlicy i Chorób Pluc, Klinki Pneumologii i Mukowiscydozy	Rabka Zdroj
Poland	Instytut Matki i Dziecka Klinika Pediatrii	Warszawa
Spain	Hospital Vall D' Hebron Pediatric Pneunmonology and Cystic Fibrosis Clinic	Barcelona
Spain	Hospital Infantil La Paz	Madrid
Spain	Hospital infantil Universitario Niño Jesus, Servicio de Neumología Pediatrica	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Materno-Infantil Carlos Haya, Servicio de Neumología Pediatrica	Malaga
United States	Akron Children's Hospital	Akron	Ohio
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Hospital Boston	Boston	Massachusetts
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Cohen Children's Medical Center of NY	Great Neck	New York
United States	PennState Milton S. Hershey Medical Center	Hershey	Pennsylvania
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 and Clinics	Kansas City	Missouri
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Nemours Childrens Clinic Orlando	Orlando	Florida
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	Saint Louis University	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Toledo Children's Hospital CF Research Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set)	The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Evaluable Analysis Set.	Day 28 to Day 196	No
Primary	Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set)	The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Sensitivity Analysis Set.	Day 28 to Day 196	No
Secondary	Change From Baseline in FEV1% Predicted	Spirometry assessments were performed only in participants = 6 years of age. Forced expiratory volume in 1 second (FEV1) % predicted was defined as FEV1 of the participant divided by the average FEV1 in the population for any person of similar age, sex and body composition.	Baseline to Days 28, 56, 112, and 196	No
Secondary	Change From Baseline in CFQ-R RSS Score	Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) only in participants = 6 years of age. The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms.	Baseline to Days 28, 56, 112, and 196	No
Secondary	Percentage of Participants With PA-negative Cultures	The percentage of participants with a PA-negative culture was summarized at each visit.	Days 28, 56, 112, and 196	No
Secondary	Use of Additional (Non-study) Antipseudomonal Antibiotics	The percentage of participants who used additional (non-study) antipseudomonal antibiotics (an indication of PA exacerbation) while on treatment and posttreatment was summarized.	Baseline to Day 196	No
Secondary	Change From Baseline in Weight		Baseline to Days 28, 56, 112, and 196	No
Secondary	Change From Baseline in Height		Baseline to Days 28, 56, 112, and 196	No
Secondary	Change From Baseline in Body Mass Index (BMI)		Baseline to Days 28, 56, 112, and 196	No
Secondary	Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam	The plasma concentration of aztreonam for participants < 6 years of age was obtained 1 hour after the first dose of AZLI on Day 1 and immediately prior to the last dose of AZLI on Day 28.	Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing)	No