SEATTLE--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq:GILD - News) today announced detailed results of its Phase III AIR-CF2 study evaluating aztreonam lysine for inhalation, an antibiotic, in patients with cystic fibrosis (CF) who have pulmonary Pseudomonas aeruginosa (P. aeruginosa). In the study, a 28-day treatment course of aztreonam lysine significantly improved the time to need for inhaled or intravenous (IV) antibiotics versus placebo. All patients received an initial 28 days of treatment with tobramycin inhalation solution prior to receiving study drug. Aztreonam lysine for inhalation was well tolerated and patients also experienced significant improvements in pulmonary function and respiratory symptoms. The data were presented by Karen S. McCoy, MD, Chief of the Division of Pediatric Pulmonology and Associate Professor of Pediatrics at The Ohio State University College of Medicine and Chief of the Section of Pulmonology at Columbus Children's Hospital, at this year's Cystic Fibrosis Therapeutics Development Network conference in Seattle, Washington. Topline results from this study were previously announced on December 19, 2006.
AIR-CF2 was a randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of a 28-day treatment course with aztreonam lysine for inhalation following a 28-day treatment course of tobramycin inhalation solution in people with CF who have pulmonary P. aeruginosa. Patients were randomized to receive 28 days of treatment with 75 mg of aztreonam lysine or volume-matched placebo each administered twice (BID) or three times (TID) daily by the eFlow® Electronic Nebulizer. Patients were followed for an overall study period of 126 days, with 56 days of observation after receiving aztreonam lysine for inhalation therapy or placebo.
Two hundred and forty-six patients were enrolled in the study and of those 211 were randomized to receive aztreonam lysine for inhalation or placebo. The mean age of patients treated with blinded study drug in the trial was 26.2 years. Participants had received more than five courses of tobramycin inhalation solution, on average, in the previous year (mean value = 5.33 courses). More than 85 percent of patients were taking medication (dornase alfa) to thin mucus secretions in the lungs and nearly 70 percent were taking oral azithromycin. At baseline, the mean percent predicted forced expiratory volume in one second (FEV1), a measure of lung function, was 55.7 percent overall, and 37 percent of patients had a predicted FEV1 less than or equal to 50 percent, indicating severe impairment of lung function.
"Pulmonary pseudomonal infection remains the leading cause of sickness and death in people with CF," said Dr. McCoy. "Data from the AIR-CF2 study indicate that aztreonam lysine for inhalation may provide broad clinical benefit, which is particularly significant given that most patients in the study had relatively long-standing CF, a history of frequent antibiotic use and impairment of lung function at the start of the study."
Two hundred and forty-six patients were enrolled in the study and of those 211 were randomized to receive aztreonam lysine for inhalation or placebo. The mean age of patients treated with blinded study drug in the trial was 26.2 years. Participants had received more than five courses of tobramycin inhalation solution, on average, in the previous year (mean value = 5.33 courses). More than 85 percent of patients were taking medication (dornase alfa) to thin mucus secretions in the lungs and nearly 70 percent were taking oral azithromycin. At baseline, the mean percent predicted forced expiratory volume in one second (FEV1), a measure of lung function, was 55.7 percent overall, and 37 percent of patients had a predicted FEV1 less than or equal to 50 percent, indicating severe impairment of lung function.
"Pulmonary pseudomonal infection remains the leading cause of sickness and death in people with CF," said Dr. McCoy. "Data from the AIR-CF2 study indicate that aztreonam lysine for inhalation may provide broad clinical benefit, which is particularly significant given that most patients in the study had relatively long-standing CF, a history of frequent antibiotic use and impairment of lung function at the start of the study."
Study Results
During the 28-day run in treatment course of tobramycin inhalation solution, patients had an average increase in improvement in FEV1 of less than 1 percent and no improvement in respiratory symptoms as measured by the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R), a patient-reported tool used to measure health-related quality of life for people with CF.
Treatment with aztreonam lysine for inhalation lengthened the time to the need for inhaled or IV antibiotics -- the primary endpoint of the study -- by a median of greater than or equal to 21 days compared to placebo (pooled p-value=0.0070 by log rank test). Physicians determined the need for antibiotics based on the presence of decreased ability to exercise, increased coughing, increased production of mucus in the lungs and/or decreased appetite, all of which are signs of exacerbation.
Aztreonam lysine-treated patients also experienced significant improvements from baseline in respiratory function, as measured by relative improvement of FEV1, with an absolute difference of 6.3 percent versus placebo (p=0.0012). These results were consistent across age groups (less than 18 years of age and greater than or equal to 18 years of age; p=0.0378 and p=0.0132, respectively).
In addition, aztreonam lysine-treated patients experienced significantly greater improvements in respiratory symptoms, as measured by the respiratory domain of the CFQ-R, than placebo-treated patients. Approximately 52 percent of aztreonam lysine for inhalation-treated patients experienced improvements exceeding the minimal clinically important difference in respiratory symptoms compared to 37 percent of placebo-treated patients (p=0.0196). AIR-CF2 is the first randomized, controlled study of an aerosolized antibiotic to include and show improvements in respiratory symptoms using the CFQ-R questionnaire.
Aztreonam lysine for inhalation was also associated with significantly greater reductions in P. aeruginosa colony forming units (a measure of the amount of bacteria present in the lungs) at 28 days compared with placebo. Pseudomonas sensitivity as measured by minimum inhibitory concentrations did not significantly change from baseline to the end of therapy in aztreonam lysine for inhalation-treated patients after 28 days of therapy.
The safety profile observed in AIR-CF2 was consistent with expected symptoms of underlying CF lung disease. The most common treatment-emergent adverse events were cough, productive cough, nasal congestion, respiratory tract congestion and wheezing. The overall rates of adverse events, drug-related adverse events and serious adverse events were similar among patients treated with aztreonam lysine for inhalation and those treated with placebo. |
