An Open-Label, Randomized, Phase 3 Trial to Evaluate the Efficacy and Safety of Aztreonam 75 mg Powder and Diluent for Nebulizer Solution (AZLI) versus Tobramycin Nebulizer Solution (TNS) in an Intermittent Aerosolized Antibiotic Regimen in Subjects with Cystic Fibrosis Followed by an Open-Label, Single-Arm Extensio

Conditions: Adult and paediatric cystic fibrosis (CF) patients with pulmonary Pseudomonas aeruginosa (PA) infection.
MedDRA version: 9.1Level: LLTClassification code 10011762Term: Cystic fibrosis

Registration Number: EUCTR2007-004277-26-GB

Lead Sponsor: Gilead Sciences Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 273

Inclusion Criteria

•Males or females aged 6 years and older
•Patients with CF as diagnosed by one of the following:
•Documented sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis test, or
•Documented sweat sodium = 60 mmol/L, or
•Two well characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, or
•Abnormal nasal potential difference with accompanying symptoms characteristic of CF
•Documented PA in an expectorated sputum or throat swab culture within 3 months prior to Visit 1 or at Visit 1
•Patients must be able to provide written informed consent/assent prior to any study related procedures; parent/guardian must be able to give written informed consent as necessary prior to any study related procedure
•Patients must have received previous treatment with aerosolized antibiotics without demonstration of drug intolerance
•FEV1 = 75% predicted at Visit 1
•Ability to perform reproducible pulmonary function tests
•Chest radiograph at Visit 1 without significant acute findings (eg, infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax); or chest radiograph or MRI obtained within the 180 days prior to Visit 1 without acute findings and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) are allowed.

Inclusion criteria for extension phase:
•Subjects must be able to provide written informed consent/assent prior to any study related procedures; parent/guardian must be able to give written informed consent as necessary prior to any study related procedures
•Subjects must have received previous treatment with aerosolized antibiotics without demonstration of drug intolerance
•Completed at least one course of AZLI or TNS during the randomized portion of the study

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

••Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day
•History of sputum or throat swab culture yielding B. cepacia in the previous 2 years
•Current requirement for daily continuous oxygen supplementation or requirement for more than 2 L/minute at night
•Administration of any investigational drug or device within 28 days of Visit 1 or within 6 half-lives of the investigational drug (whichever is longer)
•Known local or systemic hypersensitivity to monobactam antibiotics
•Known allergies/intolerance to tobramycin
•Inability to tolerate inhalation of a short acting ß2 agonist
•Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
•Administration of antipseudomonal antibiotics by inhalation, intravenous or oral routes within the 14 days prior to Visit 1
•Changes in antimicrobial, bronchodilator (BD), dornase alfa, or corticosteroid medications within 7 days prior to Visit 1
•Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
•History of lung transplantation
•Abnormal renal or hepatic function or serum chemistry at Visit 1, defined as:
- AST, ALT > 5 times upper limit of normal range (ULN)
- Creatinine > 2 times ULN
•Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
•Female of childbearing potential who is lactating or is not (in the opinion of the investigator) practicing an acceptable method of birth control; female subjects who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least 3 months before study dosing
•Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol

Exclusion criteria for extension phase:
•Known local or systemic hypersensitivity to monobactam antibiotics
•Inability to tolerate inhalation of a short acting ß2 agonist
•Positive urine pregnancy test; all women of childbearing potential will be tested
•Female of childbearing potential who is lactating or is not (in the opinion of the investigator) practicing an acceptable method of birth control
•Concurrent participation in a study of another investigational medication or device
•Use of another investigational product (with the exception of AZLI) within the last 28 days
•Terminated early from the randomized portion of the study, but not yet reached the 6 month time point for entry into the AZLI extension phase