Abstract
Background
Methods
Results
Conclusions
Keywords
1. Introduction
- Oermann C.M.
- Retsch-Bogart G.Z.
- Quittner A.L.
- Gibson R.L.
- McCoy K.S.
- Montgomery A.B.
- et al.
2. Methods
2.1 Study design
2.2 Participants
2.3 Study endpoints
2.4 Statistical analysis
3. Results
3.1 Disposition

3.2 Patient characteristics
AZLI-treated n=136 | TNS-treated n=132 | Overall n=268 | |
---|---|---|---|
Region; n (%) | |||
Europe | 92 (67.6) | 82 (62.1) | 174 (64.9) |
United States | 44 (32.4) | 50 (37.9) | 94 (35.1) |
Age, years; mean (SD) | 25.8 (9.1) | 25.1 (9.0) | 25.5 (9.0) |
Age group; n (%) | |||
6 to 12 years | 8 (5.9) | 5 (3.8) | 13 (4.9) |
>12 to <18 years | 20 (14.7) | 26 (19.7) | 46 (17.2) |
≥18 years | 108 (79.4) | 101 (76.5) | 209 (78.0) |
Male gender; n (%) | 68 (50.0) | 66 (50.0) | 134 (50.0) |
White race; n (%) | 130 (95.6) | 131 (99.2) | 261 (97.4) |
Body mass index, kg/m2; mean (SD) | 20.2 (3.0) | 20.5 (2.8) | 20.4 (2.9) |
CFTR genotype; n (%) | |||
Homozygous for ∆508 | 64 (54.7) | 60 (54.1) | 124 (54.4) |
Heterozygous for ∆508 | 36 (30.8) | 30 (27.0) | 66 (28.9) |
Unidentified or other | 17 (14.5) | 21 (18.9) | 38 (16.7) |
FEV1% predicted at screening; n (%) | |||
>50% to ≤75% | 76 (55.9) | 75 (56.8) | 151 (56.3) |
≤50% | 60 (44.1) | 57 (43.2) | 117 (43.7) |
<25% | 6 (4.4) | 6 (4.5) | 12 (4.5) |
Inhaled tobramycin use in previous year; n (%) | |||
<84 days | 21 (15.4) | 19 (14.4) | 40 (14.9) |
≥84 days | 115 (84.6) | 113 (85.6) | 228 (85.1) |
Inhaled colistin use in previous year; n (%) | 50 (36.8%) | 53 (40.2%) | 103 (38.4%) |
Azithromycin use at baseline; n (%) | 85 (62.5) | 89 (67.4) | 174 (64.9) |
Dornase alfa use at baseline; n (%) | 92 (67.6) | 91 (68.9) | 183 (68.3) |
Hypertonic saline use at baseline; n (%) | 44 (32.4) | 46 (34.8) | 90 (33.6) |
Baseline values; mean (SD) | |||
FEV1% predicted | 52.3 (15.6) | 52.2 (14.6) | 52.3 (15.1) |
FEV1 (L) | 1.8 (0.6) | 1.8 (0.6) | 1.8 (0.6) |
Log10 PA CFU per g sputum | 6.4 (2.1) | 5.9 (2.7) | 6.2 (2.4) |
CFQ-R respiratory symptoms score | 62.9 (20.4) | 58.0 (20.8) | 60.4 (20.7) |
MIC of aztreonam for all PA isolates at baseline | |||
MIC50; μg/mL | 2 | 2 | 2 |
MIC90; μg/mL | 32 | 128 | 64 |
Minimum MIC; μg/mL | ≤1 | ≤1 | ≤1 |
Maximum MIC; μg/mL | >2048 | 2048 | >2048 |
Isolates tested; n | 208 | 198 | 406 |
MIC of tobramycin for all PA isolates at baseline | |||
MIC50; μg/mL | 2 | 2 | 2 |
MIC90; μg/mL | 64 | 64 | 64 |
Minimum MIC; μg/mL | ≤0.12 | ≤0.12 | ≤0.12 |
Maximum MIC; μg/mL | >1024 | >1024 | >1024 |
Isolates tested; n | 208 | 198 | 406 |
Multi-drug resistant PA;, g n (%)Resistance assessed using CF Foundation definition: resistance to all antibiotics tested in 2 of the 3 drug classes (aminoglycosides, beta-lactams, quinolones) [18]. CFQ-R = cystic fibrosis questionnaire—revised; CFTR = cystic fibrosis transmembrane conductance regulator; CFU = colony forming units; FEV1 = forced expiratory volume in 1s; MIC = minimum inhibitory concentration; PA = Pseudomonas aeruginosa. | 35 (30.4) | 35 (31.8) | 70 (31.1) |
- Saiman L.
- Siegel J.
- the CF Foundation Consensus Conference on Infection Control Participants
3.3 Efficacy — active-comparator period

Endpoint | AZLI-treated n=136 | TNS-treated n=132 | p-Value |
---|---|---|---|
Time to need for IV antipseudomonal antibiotics for respiratory events | |||
Median number of days (95% CI) | NE (177, NE) | 151 (113, NE) | 0.003 |
Event rate at Week 24 (end of active-comparator period), % | 36 | 54 | |
Time-to-first respiratory hospitalization | |||
Median number of days (95% CI) | NE (NE, NE) | NE (NE, NE) | 0.111 |
Event rate at Week 24 (end of active-comparator period), % | 24 | 31 | |
CFQ-R respiratory symptoms scale, change from baseline score, adjusted mean (SE) | |||
Week 4 (after course 1; AZLI: n=131; TNS: n=131) | 8.2 (1.7) | 2.6 (1.7) | 0.005 |
Average across 3 courses (Weeks 4, 12, 20; AZLI: n=131; TNS: n=131) | 6.3 (1.5) | 2.2 (1.5) | 0.019 |
Number of respiratory hospitalizations | 40 | 58 | 0.044 |
Number of respiratory events requiring IV and/or additional inhaled antipseudomonal antibiotics | 84 | 121 | 0.004 |
Patients requiring IV and/or additional inhaled antipseudomonal antibiotics for respiratory events, n (%) | 52 (38.2) | 76 (57.6) | 0.002 |
Time to need for IV or additional inhaled antipseudomonal antibiotics for respiratory events | |||
Median number of days (95% CI) | NE (177, NE) | 117 (102, 169) | <0.001 |
Event rate at Week 24 (end of active-comparator period), % | 38 | 58 | |
Days of oral, IV, and/or additional inhaled antipseudomonalantibiotic use, mean (SD) | 21.3 (24.8) | 28.4 (31.5) | 0.060 |
Log10 PA CFU/g sputum, change from baseline, adjusted mean (SE) | |||
Week 4 (after course 1; AZLI: n=88; TNS: n=94) | −0.60 (0.23) | −0.34 (0.23) | 0.330 |
Average across 3 courses (Weeks 4, 12, 20; AZLI: n=97; TNS: n=97) | −0.55 (0.19) | −0.32 (0.19) | 0.295 |
Weight, relative change from baseline at Week 24 (end of active‐comparator period), %, adjusted mean (SE) | 0.58 (0.41) | 0.06 (0.43) | 0.289 |
TSQM scales, Week 4 (after course 1), adjusted mean (SE) | |||
Effectiveness (AZLI: n=131; TNS: n=126) | 69.5 (1.9) | 56.9 (2.0) | <0.001 |
Side-effects (AZLI: n=130; TNS: n=126) | 91.6 (1.6) | 89.2 (1.7) | 0.204 |
Convenience (AZLI: n=129; TNS: n=125) | 72.2 (2.1) | 67.2 (2.1) | 0.041 |
Global satisfaction (AZLI: n=130; TNS: n=126) | 68.9 (2.1) | 61.8 (2.2) | 0.004 |
TSQM scales, Week 20 (after course 3), adjusted mean (SE) | |||
Effectiveness (AZLI: n=118; TNS: n=110) | 73.4 (2.3) | 57.9 (2.5) | <0.001 |
Side-effects (AZLI: n=118; TNS: n=107) | 94.3 (1.6) | 92.5 (1.7) | 0.328 |
Convenience (AZLI: n=118; TNS: n=107) | 68.0 (2.2) | 66.1 (2.4) | 0.460 |
Global satisfaction (AZLI: n=118; TNS: n=109) | 75.8 (4.6) | 61.7 (4.9) | 0.010 |

3.4 Efficacy — extension period
3.5 Safety
Incidence of adverse event, n (%) | ||
---|---|---|
Adverse event | AZLI-treated n=136 | TNS-treated n=132 |
Cough | 96 (70.6) | 104 (78.8) |
Productive cough | 70 (51.5) | 79 (59.8) |
Pyrexia | 43 (31.6) | 40 (30.3) |
Oropharyngeal pain | 36 (26.5) | 37 (28.0) |
Dyspnea | 32 (23.5) | 36 (27.3) |
Hemoptysis | 31 (22.8) | 21 (15.9) |
Rales | 30 (22.1) | 35 (26.5) |
Headache | 29 (21.3 ) | 27 (20.5) |
Nasal congestion | 29 (21.3) | 26 (19.7) |
Rhinorrhea | 25 (18.4 ) | 33 (25.0) |
Exercise tolerance decreased | 25 (18.4) | 27 (20.5) |
Fatigue | 24 (17.6) | 25 (18.9) |
Decreased appetite | 19 (14.0) | 19 (14.4) |
Abdominal pain | 18 (13.2) | 8 (6.1) |
Respiratory tract congestion | 16 (11.8) | 19 (14.4) |
Wheezing | 16 (11.8) | 20 (15.2) |
Chest discomfort | 14 (10.3) | 13 (9.8) |
Nausea | 14 (10.3) | 10 (7.6) |
Vomiting | 14 (10.3) | 14 (10.6) |
Pulmonary function test decreased | 11 (8.1) | 17 (12.9) |
Breath sounds abnormal | 8 (5.9) | 15 (11.4) |
3.6 Microbiology
4. Discussion
- Oermann C.M.
- Retsch-Bogart G.Z.
- Quittner A.L.
- Gibson R.L.
- McCoy K.S.
- Montgomery A.B.
- et al.
5. Study investigators
Conflict of interest statement
Role of the Funding Source
Acknowledgments
Appendix A. Supplementary data
Online Supplementary Material Figure Legends.
- Online Fig. 1
Study design. “AZLI” and “TNS” represent 28-day treatment periods. Each treatment period was followed by 28-days without study medication (“Off”).
- Online Fig. 2
Relative change from baseline FEV1% predicted at Day 28 for patient subgroups. The adjusted means are from an ANCOVA model that included terms for treatment, baseline FEV1% predicted, and previous inhaled tobramycin use. Missing data were imputed with the last observation carried forward method. The US patient subgroup did not include any patients with inhaled tobramycin use <84 days in the previous year. At the bottom of the figure, the SE bars for the TNS and AZLI data sets overlap for patients <18 years of age and for patients with prior inhaled tobramycin use <84 days. Moderate disease severity=FEV1>50% to ≤75% predicted at baseline and severe disease severity=FEV1≤50% predicted at baseline.
- Online Fig. 3
Adjusted mean relative change in body weight (%) from study baseline by study visit for patients participating in the AZLI open-label extension period. Significant differences between the AZLI and TNS treatment groups were observed at Week 4 (p=0.004), Week 12 (p=0.003), and Week 16 (p=0.009).
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Article info
Publication history
Footnotes
☆Study results were reported at the 24th Annual North American Cystic Fibrosis Conference, Baltimore Convention Center, Baltimore, Maryland, USA, 21–23 October 2010; the American Thoracic Society 2011 International Conference, Denver, Colorado, USA, 13–18 May 2011; the 34th European Cystic Fibrosis Conference, Hamburg, Germany, 8–11 June 2011; and the 25th Annual North American Cystic Fibrosis Conference, Anaheim, California, USA, 3–5 November 2011.
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