Inhaled Fosfomycin/Tobramycin for People with CF and P. aeruginosa
Number of Participants Being Recruited:
Single / Multi-Center:
STUDY BACKGROUND INFORMATION:
Gilead is developing a new inhaled broad spectrum combination antibiotic (FTI) consisting of fosfomycin (an antibiotic with activity against gram-positive and gram-negative bacteria) and tobramycin (an aminoglycoside antibiotic with potent gram-negative activity) for treatment of patients with CF. This study will evaluate the safety and efficacy of 2 dose combinations of fosfomycin/tobramycin for inhalation (FTI), following a 28-day course of Aztreonam for Inhalation (AZLI) in patients with cystic fibrosis and Pseudomonas aeruginosa lung infection.
>= 18 Years
25 - 75 Percent Predicted
P. aeruginosa status:
B. cepacia status:
Other Primary Eligibility Requirements:
Note: Detailed eligibility criteria information may be available on clinicaltrials.gov. If a specific
trial listing for this trial is available, a link to the specific clinicaltrials.gov listing will be present in the "More Information" section below.
One hundred thirty-five CF subjects (age >/=18 years) with pulmonary PA were enrolled in this Phase 2 study to evaluate safety and efficacy of Fosfomycin/Tobramycin for inhalation (FTI). Subjects received open-label CaystonÂ® (75 mg TID) for 28-days before being randomized to treatment with either FTI 80/20mg or FTI 160/40mg or placebo BID for 28 days. The trial met its primary efficacy endpoint: after 28 days of treatment, the FTI 160/40 mg dosing group maintained the improvement in FEV1 % predicted achieved by the 28-day AZLI run-in period, in contrast to the placebo treatment group, where lung function declined toward pre-AZLI levels. The treatment effect was 6.2% favoring FTI (p=0.002).
FEV1 % predicted was also maintained in the FTI 80/20 mg dosing group. The treatment effect on mean PA sputum density was statistically significant for the FTI 80/20 mg group versus placebo. The proportion of patients hospitalized and the number of hospitalization days did not differ significantly between treatment groups over the course of the study. Improvement in respiratory symptoms achieved by the AZLI run-in, as measured by the CFQ-R and RSSQ, was better maintained in the FTI 80/20 mg treatment group than in the FTI 160/40 mg or placebo groups.
FTI was well tolerated. Adverse events, primarily cough, were consistent with CF disease. The FTI 80/20 mg group was more likely to complete treatment and reported fewer respiratory AEs than those in the FTI 160/40 group.