Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis

Abstract

Background: Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population.

Methods: Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group.

Results: The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115).

Conclusions: Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF.

Trial registration number: Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

Keywords: Cystic Fibrosis.

Figure 1

Study design (A) and subject disposition (B). (A) Subjects were stratified based on maintenance macrolide usage and randomised 2:2:2:1 to receive twice daily: 32.5 mg ciprofloxacin DPI (corresponding to 50 mg dry powder); placebo corresponding to 32.5 mg ciprofloxacin DPI; 48.75 mg ciprofloxacin DPI (corresponding to 75 mg dry powder); or placebo corresponding to 48.75 mg ciprofloxacin DPI for 29 days (±1 day). DPI, dry powder for inhalation; EOT, end of treatment. (B) A total of 288 patients were randomised. Of these, 286 received either study drug or placebo, and were included in both the ITT and safety analyses sets. ITT, intent-to-treat.

Figure 2

Time course of FEV1 (mean, % predicted) (intent-to-treat population) by study group. Empirical mean FEV1 is presented as percentage predicted value, with error bars representing SD. DPI, dry powder for inhalation; FEV1, forced expiratory volume in 1 s.

Figure 3

Change in mean density of Pseudomonas aeruginosa in sputum (log₁₀CFU/g) (intent-to-treat population) by study group. CFU, colony-forming unit; DPI, dry powder for inhalation.