Study Evaluating Fosfomycin/Tobramycin for Inhalation in Cystic Fibrosis Patients With Pseudomonas Aeruginosa Lung Infection

Inclusion Criteria:

• Males or females aged 18 years and older

• Patients 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
  • Abnormal nasal potential difference, OR
  • Two well-characterized genetic mutations in the CF transmembrane conductance regulator (CFTR) gene, AND
  • Accompanying symptoms characteristic of CF
• Documented presence of PA in an expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within 12 months prior to Visit 1; one of the previous PA-positive cultures must be within 3 months prior to Visit 1
• Patients must be able to provide written informed consent prior to any study related procedures
• FEV1 greater than or equal to 25% and less than or equal to 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, CT, or MRI obtained within the 90 days prior to Visit 1 without acute findings or significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed.

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 or other aminoglycosides
• Known allergies/intolerance to fosfomycin
• Inability to tolerate inhalation of a short acting beta2 agonist
• Changes in or initiation of chronic azithromycin treatment within 14 days prior to Visit 1
• Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes within the 14 days prior to Visit 1
• Changes in antimicrobial, bronchodilator (BD), corticosteroid, hypertonic saline, or dornase alfa 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 > 3 times upper limit of normal range (ULN)
  • Creatinine > 1.5 times ULN
• Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
• Female patients of childbearing potential who are lactating or are not (in the opinion of the investigator) practicing an acceptable method of birth control; female patients who utilize hormonal contraceptives as a birth control method 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