Cystic Fibrosis subjects with chronic Burkholderia spp. infection of the airways. MedDRA version: 17.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 6 years of age 2. Subjects with CF as diagnosed by one of the following: — Documented sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis test — Documented sweat sodium = 60 mmol/L — Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene — Abnormal NPD with accompanying symptoms characteristic of CF 3. Chronic infection with Burkholderia spp. defined by: — One sputum (or bronchoalveolar lavage) culture positive for Burkholderia spp. within 6 months prior to baseline assessment, — At least 50% of sputum (or bronchoalveolar lavage) cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and — At least one positive sputum (or bronchoalveolar lavage) culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory) Subjects with oro-pharyngeal cultures rather than sputum culture results available in the previous 12 months will meet the above criteria for chronic infection with Burkholderia spp. if: — There is at least one documented prior lower respiratory tract culture(s) (expectorated, induced sputum or bronchoalveolar lavage) positive for Burkholderia spp. (obtained at any time point), and — There is concordance of the species isolated from at least one prior lower respiratory tract cultures (obtained at any time point) and recent oropharyngeal cultures (obtained in the previous 12 months) 4. Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction on their aerosolized antibiotic treatment 5. Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed 6. Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures 7. Ability to perform reproducible pulmonary function tests 8. Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug; a highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner Are the trial subjects under 18? yes Number of subjects for this age range: 17 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 83 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer) 2. Administration of AZLI treatment within the 28 days prior to randomization/baseline 3. Known local or systemic hypersensitivity to monobactam antibiotics 4. History of lung transplantation 5. Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as: — AST or ALT > 5 times upper limit of normal (ULN) range — Serum creatinine > 2 times ULN 6. Known portal hypertension or complications of CF hepatopathy 7. Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested 8. Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8 9. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the safety and efficacy of continuous AZLI treatment in subjects with CF and Burkholderia spp. infection in the airways.;Secondary Objective: • Effect of continuous AZLI use on microbial resistance • Suppressive effect of AZLI on Burkholderia spp. • Safety of AZLI administered TID for up to 48 weeks;Primary end point(s): The primary endpoint is the relative change from baseline in FEV1 percent predicted as measured by the AUCave through Week 24.;Timepoint(s) of evaluation of this end point: Week 24 of study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • AUCave of relative change from baseline in FEV1, FVC, and FEF25-75 through Week 24 • AUCave of change from baseline in clinical symptoms as assessed by the respiratory symptoms domain of the CFQ-R through Week 24 • AUCave of change from baseline in clinical symptoms as assessed by the non-respiratory domains of the CFQ-R through Week 24 • Change from baseline in BMI at Week 24 • Change from baseline in Burkholderia spp. CFUs in sputum at Week 24 • Use of systemic antibiotics through Week 24 of the study • Percent of days subjects used systemic antibiotics through Week 24 of the study • Percent of days subjects were hospitalized through Week 24 of the study • Percent of days lost from school or work through Week 24 of the study;Timepoint(s) of evaluation of this end point: Week 24 of study. | — |
Countries
Canada, United States
Contacts
Public ContactClinical Trials Information
Gilead Sciences International Ltd
Outcome results
None listed