Abstract
Introduction:
Bronchiectasis is a neglected disease in respiratory medicine. In adult NCFBE patients, PA infections are associated with an increased risk of death, hospital admissions and exacerbations. There is no approved treatment to prevent pulmonary exacerbations (PE) in bronchiectasis.
Methods:
Pulmaquin, a once-a-day inhaled dual-release formulation composed of both liposome encapsulated and unencapsulated ciprofloxacin, is being evaluated in two Phase 3 trials in patients with CT-scan documented NCFBE who have chronic lung infections with PA. The subjects must have had at least 2 PEs in the 12 months prior to enrollment, and a positive sputum sample with at least one PA isolate nonresistant to ciprofloxacin. Each trial has a 48-week double blind period of 6 cycles of 28 days on and 28 days off treatment comparing Pulmaquin against placebo, followed by a 28-day open label extension with Pulmaquin. The primary endpoint is time to first PE during the double blind period and key secondary endpoints are the number of PEs, severe PEs and quality of life. Microbiology assessments (PA density, ciprofloxacin MIC for PA, isolation and quantification of other selected pathogens, PA sensitivity testing to selected antibiotics), ciprofloxacin serum levels, 6 minute walk test and productivity questions are conducted. Spirometry and DLCO are monitored as safety indicators. PEs are assessed based on protocol specified symptoms, signs, or laboratory findings.
Results:
1046 subjects were screened in the U.S., Canada, Australia, New Zealand, Israel, South Korea, Taiwan, South Africa, U.K., Germany, France, Spain, Italy, Ireland, Georgia, Serbia, Poland, Romania, Latvia and Peru. Both studies completed enrollment with a total of 584 subjects randomized and dosed.
Conclusion:
The two well-controlled clinical trials will provide a large database of well-defined NCFBE subjects with chronic PA colonization to investigate the effect of Pulmaquin on the prevention of PEs using a rigorous definition of exacerbation.