Cystic Fibrosis
Conditions
Interventions
- Three cycles of AML 75 mg TID for 28 days, followed by no treatment for 28
days
- Three cycles of TNS 300 mg BID for 28 days, followed by no treatment for 28
days
Sponsors
Gilead Sciences
Eligibility
Age
2 Years to 99 Years
Inclusion 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 * 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 * 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
Exclusion criteria
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 *2 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary study endpoint was change in patient-reported respiratory symptoms between Days 0 and 28, as determined by the CFQ-R respiratory domain. The primary efficacy endpoint is the relative change in FEV1 percent predicted at Day 28 compared to baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints The key secondary endpoints are: - Change from baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale at Day 28 - Relative change from baseline in FEy1 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 Additional efficacy endpoints to be evaluated are: - 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 | — |
Countries
Netherlands
Outcome results
None listed