Background A light-porous-particle, dry-powder formulation of tobramycin was developed, using PulmoSphere® technology, to improve airway delivery efficiency, substantially reduce delivery time, and improve patient convenience and satisfaction. We evaluated the safety, efficacy and convenience of tobramycin inhalation powder (TIP™) versus tobramycin inhalation solution (TIS, TOBI®) for treating Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients aged ≥6 years. Methods In this open-label study, 553 patients were randomized 3:2 to TIP (total 112 mg tobramycin) via the Novartis T-326 Inhaler or TIS 300 mg/5 mL via PARI LC® PLUS nebulizer twice daily for three treatment cycles (28 days on-drug, 28 days off-drug). Safety, efficacy, and treatment satisfaction outcomes were evaluated. Results TIP was generally well-tolerated; adverse events were similar in both groups. The rate of cough suspected to be study-drug related was higher in TIP-treated patients (TIP: 25.3%; TIS: 4.3%), as was the overall discontinuation rate (TIP: 26.9%; TIS: 18.2%). Increases in FEV1 % predicted from baseline to Day 28 of Cycle 3 were similar between groups; mean reduction in sputum Pseudomonas aeruginosa density (log10 CFU/g) on Day 28 of Cycle 3 was also comparable between groups. Administration time was significantly less for TIP (mean: 5.6 versus 19.7 minutes, p<0.0001). Treatment satisfaction was significantly higher for TIP for effectiveness, convenience, and global satisfaction. Conclusions TIP has a safety and efficacy profile comparable with TIS, and offers a far more convenient treatment option for pseudomonas lung infection in CF.

Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients. We evaluated the efficacy and safety of a novel, light-porous-particle, dry-powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double-blind study, patients with cystic fibrosis (age 6–21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T-326 Inhaler for one cycle, followed by two open-label cycles (all patients). Cycles were 28 days on, 28 days off treatment. The primary endpoint was change in FEV1 % predicted from baseline to Day 28 of Cycle 1. The study was terminated early based on positive results in the interim analysis. Tobramycin inhalation powder significantly improved FEV1 % predicted versus placebo at Day 28 (difference 13.3, 95% CI 5.31, 21.28; P = 0.0016). Similar changes in FEV1 were seen in patients switching from placebo to tobramycin inhalation powder in Cycle 2; improvements were maintained over time. Tobramycin inhalation powder also reduced sputum Pseudomonas aeruginosa density, respiratory-related hospitalization and antipseudomonal antibiotic use versus placebo. The most common adverse event was cough; the frequency of cough was higher in patients receiving placebo (26.5%) versus tobramycin inhalation powder (13.0%) in Cycle 1. Tobramycin inhalation powder was not associated with ototoxicity or nephrotoxicity. Administration time was between 4 and 6 minutes. In conclusion, tobramycin inhalation powder was effective and well tolerated in cystic fibrosis patients, and may offer an important treatment option to decrease the treatment burden of cystic fibrosis pseudomonas lung infections.

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1,3,10, 30, 50, 75, 150, 300 Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.

In patients with cystic fibrosis (CF), respiratory infections with the opportunistic bacterial pathogen Pseudomonas aeruginosa have a major impact on morbidity and mortality. Aminoglycosides, especially tobramycin, have been used successfully to combat these infections. Aminoglycoside penetration of bronchial secretions is poor when the antibiotic is administered intravenously. Nebulization allows direct delivery of the drug to the sites of infection within the airways, while avoiding systemic exposure. Published clinical data show that inhaled tobramycin reduces the bacterial load, improves lung function and reduces the number of hospital admissions. Inhaled tobramycin has been used successfully to eradicate P. aeruginosa in patients with early infection. Maintaining clinical benefits requires chronic tobramycin treatment, and the concept of chronic intermittent inhaled treatment (typically, alternating drug and drug-free periods of 28 days) was introduced to minimize the emergence of aminoglycoside resistant P. aeruginosa strains. Other therapeutic advances include the development of different tobramycin formulations and nebulizers that reduce delivery time without compromising efficacy. An optimal treatment regimen for patients with CF with early or intermittent P. aeruginosa infections remains a high priority to maintain long-term lung health.

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