Figures
- Figure 1–
Study design and subject disposition. Protocol violations in screening failures included no positive culture (n=23), inadequate sputum (n=50), forced expiratory volume in 1 s outside range (n=6), exacerbations during screening (n=2), on antibacterials (n=6), no further information (n=25) and other (n=10). DPI: dry powder for inhalation.
- Figure 2–
Mean bacterial load for the a) modified intent-to-treat population and b) per-protocol populations. Only results from valid cultures were considered. Cultures were excluded if subjects were administered concomitant antibacterials, if there were >25 squamous epithelial cells in the absence of Pseudomonas aeruginosa or if there were ≤25 leukocytes for P. aeruginosa-negative cultures pre-therapy. DPI: dry powder for inhalation. Shaded area indicates treatment period (days). #: number of patients with valid sputum cultures. ***: p<0.001.
- Figure 3–
Mean colony count of selected pathogens at baseline and at end of treatment. Only results from valid cultures were considered. Cultures were excluded if subjects were administered concomitant antibacterials, if there were >25 squamous epithelial cells in absence of Pseudomonas aeruginosa or if there were ≤25 leukocytes for P. aeruginosa-negative cultures pre-therapy. DPI: dry powder for inhalation; EOT: end of treatment.
- Figure 4–
Occurrence of exacerbations requiring antibacterial intervention throughout the study (modified intent-to-treat population). 22 subjects in the ciprofloxacin DPI group and 25 subjects in the placebo group experienced an exacerbation. Of these, 14 subjects in the ciprofloxacin DPI group and 18 subjects in the placebo group required antibacterial treatment. DPI: dry powder for inhalation. Shaded area indicates treatment period (days).
Tables
- Table 1– Demographic and baseline data (modified intent-to-treat/safety population)
Characteristic Ciprofloxacin DPI Placebo Subjects n 60 64 Age years 64.7±11.8 61.4±11.9 Sex Male 21 (35.0) 21 (32.8) Female 39 (65.0) 43 (67.2) Ethnicity Caucasian 60 (100.0) 63 (98.4) Asian 0 1 (1.6) Weight kg 70.2±16.4 69.1±17.2 BMI kg·m−2 25.6±5.5 25.1±5.6 FEV1 % pred 57.2±13.7 54.6±14.8 Subjects with exacerbations in previous 12 months 1–2 exacerbations 30 (50.0) 35 (54.7) 3–4 exacerbations 25 (41.7) 26 (40.6) ≥5 exacerbations 5 (8.3) 3 (4.7) Baseline total bacterial load log10 CFU·g−1 7.19±1.94 6.92±1.90 Baseline bacterial isolates in ≥5% subjects# Pseudomonas aeruginosa 32 (53.3) 35 (54.7) Haemophilus influenzae 14 (23.3) 16 (25.0) Staphylococcus aureus 8 (13.3) 17 (26.6) Streptococcus pneumoniae 7 (11.7) 2 (3.1) Moraxella catarrhalis 5 (8.3) 3 (4.7) Klebsiella pneumoniae 5 (8.3) 0 Proteus mirabilis 3 (5.0) 4 (6.3) Klebsiella oxytoca 3 (5.0) 2 (3.1) Data are presented as mean±sd or n (%), unless otherwise stated. DPI: dry powder for inhalation; BMI: body mass index; FEV1: forced expiratory volume in 1 s; % pred: % predicted. #: no significant differences between ciprofloxacin DPI and placebo for isolates were reported apart from for K. pneumoniae (p=0.024).
- Table 2– Number of subjects with eradication (negative bacterial culture, modified intent-to-treat population)
Time period Ciprofloxacin DPI Placebo p-value# During treatment visit (day 8) 20/42 (47.6) 6/51 (11.8) <0.001 End of treatment (day 29) 14/40 (35.0) 4/49 (8.2) 0.001 2-week follow-up (day 42) 6/36 (16.7) 4/37 (10.8) 0.359 4-week follow-up (day 56) 4/31 (12.9) 1/28 (3.6) 0.617 8-week follow-up (day 84) 4/27 (14.8) 2/25 (8.0) 0.763 Data are presented as n/N (%), unless otherwise stated. DPI: dry powder for inhalation. #: based on Cochran–Mantel–Haenszel test stratified by centre/cluster of centre.
- Table 3– Sputum colour in the modified intent-to-treat/safety population with available sputum samples
Ciprofloxacin DPI Placebo p-value Baseline total subjects 60 63# 0.220¶ No sputum/clear 5 (8.3) 7 (11.1) Yellow 29 (48.3) 23 (36.5) Green 25 (41.7) 28 (44.4) Rust 1 (1.7) 5 (7.9) End of treatment 49 52 0.026¶, 0.029+ No sputum/clear 12 (24.5) 9 (17.3) Yellow 31 (63.3) 26 (50.0) Green 5 (10.2) 17 (32.7) Rust 1 (2.0) 0 4-week follow-up 40 37 0.494¶, 0.609+ No sputum/clear 10 (25.0) 5 (13.5) Yellow 16 (40.0) 22 (59.5) Green 11 (27.5) 9 (24.3) Rust 3 (7.5) 1 (2.7) Data are presented as n or n (%), unless otherwise stated. DPI: dry powder for inhalation. #: no sputum information was available for one patient; ¶: based on Cochran–Mantel–Haenszel test with ridit scores test stratified by centre/cluster of centre; +: based on Cochran–Mantel–Haenszel test with ridit scores test stratified by centre/cluster of centre and baseline sputum colour.
- Table 4– Summary of adverse events (AEs) (modified intent-to-treat/safety population)
AE Ciprofloxacin DPI Placebo p-value Subjects n 60 64 Subjects with any AEs 50 (83.3) 54 (84.4) 1.000 Patients with any treatment-emergent AEs 41 (68.3) 42 (65.6) 0.849 Patients with treatment-related AEs 21 (35.0) 17 (26.6) 0.335 Treatment-emergent AEs reported in >5% subjects Product taste abnormal 8 (13.3) 7 (10.9) 0.786 Dysgeusia 4 (6.7) 1 (1.6) 0.197 Cough 0 5 (7.8) 0.058 Exacerbation of bronchiectasis 7 (11.7) 14 (21.9) 0.155 Headache 4 (6.7) 5 (7.8) 1.000 Subjects with treatment-emergent serious AEs# 2 (3.3) 3 (4.7) 1.000 Complex pain syndrome 1 (1.7) 0 0.484 Hallucination 1 (1.7) 0 0.484 Exacerbation of bronchiectasis 0 3 (4.7) 0.245 Sepsis 0 1 (1.6) 1.000 Deaths 0 0 Data are presented as n (%), unless otherwise stated. DPI: dry powder for inhalation. #: none considered to be drug related.
Supplementary material
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- Supplementary material -
Materials and methods
Results � modified intent-to-treat analysis set
Results � per-protocol analysis set
- Supplementary material -
Disclosures
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