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

• Register: EUCTR
• Last refreshed on: 10 July 2012
• Main ID: EUCTR2007-004277-26-NL
• Date of registration: 29/05/2008
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences Inc
• Public title: An Open-Label, Randomized, Phase 3 Trial to Evaluate the Efficacy and Safety of Aztreonam 75 mg Powder and Diluent for Nebuliser Solution (AZLI) versus Tobramycin Nebuliser Solution (TNS) in an Intermittent Aerosolized Antibiotic Regimen, in subjects with Cystic Fibrosis followed by an Open-Label, Single Arm Extension
• Scientific title: An Open-Label, Randomized, Phase 3 Trial to Evaluate the Efficacy and Safety of Aztreonam 75 mg Powder and Diluent for Nebuliser Solution (AZLI) versus Tobramycin Nebuliser Solution (TNS) in an Intermittent Aerosolized Antibiotic Regimen, in subjects with Cystic Fibrosis followed by an Open-Label, Single Arm Extension
• Date of first enrolment: 10/06/2008
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004277-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in the randomized portion of this study.
• Males or females aged 6 years and older
• Subjects with CF as diagnosed by one of the following:
- Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test, or
- Documented sweat sodium greater than or equal to 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
• 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 procedure
• Subjects 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 (e.g., 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 (e.g., chronic scarring or atelectasis) are allowed

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:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
• 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 Beta2 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 Randomization/Visit 2.
• 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 subject treatment, assessment, or compliance with the protocol



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Product Name: AZLI
Pharmaceutical Form: Powder for nebuliser solution
INN or Proposed INN: aztreonam lysine
Current Sponsor code: AZLI
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-

Trade Name: TOBI
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: tobramycin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Primary end point(s): Relative change from baseline in FEV1 percent of predicted at Day 28.

Main Objective: To assess the comparative safety and efficacy of Aztreonam 75 mg Powder and Diluent for Nebuliser Solution (AZLI) and Tobramycin Nebuliser Solution (TNS) in adult and pediatric cystic fibrosis (CF) subjects with pulmonary Pseudomonas aeruginosa (PA) infection.

Secondary Objective: • Change from baseline in the Cystic Fibrosis Questionnaire – Revised (CFQ-R) Respiratory Symptoms Scale at Day 28
• Relative change from baseline in FEV1 percent of predicted at Week 20 (end of last treatment course of AZLI or TNS)
• Use of additional (non-protocol specified) antipseudomonal antibiotics during the course of the study
• Hospitalizations during the course of the study
• Change in PA CFUs in sputum at the end of each on-drug cycle
• Changes from baseline in FEV1, FVC and FEF 25-75 at each study visit
• Change from baseline in other domains as assessed by the CFQ-R at each visit
• Changes from baseline in weight and Body Mass Index (BMI) at each visit
• Missed school/work days during the course of the study
Treatment Satisfaction Questionnaire for Medication (TSQM) at Day 28 and either Day 140 or ET

Secondary ID(s)

GS-US-205-0110

2007-004277-26-BE