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.

Rationale Antibiotic therapy for early Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is effective, but the optimal therapeutic regimen and duration for early treatment remains unclear. The EarLy Inhaled Tobramycin for Eradication (ELITE) study was designed to assess the efficacy and safety of two regimens (28 and 56 days) of tobramycin inhalation solution (TIS) 300 mg/5 ml twice daily for the treatment of early onset P aeruginosa infection in patients with CF.Methods In this open-label randomised multicentre study, patients with CF (aged $6 months) with early P aeruginosa infection were treated for 28 days with TIS twice daily administered by the PARI LC PLUS (PARI GmbH, Starnberg, Germany) jet nebuliser. After 28 days, patients were randomised 1:1 to either stop TIS (n¼45) or to receive a further 28 days of TIS (n¼43). The primary endpoint was the median time to recurrence of P aeruginosa (any strain). Secondary endpoints included the proportion of patients free of P aeruginosa infection 1 month after cessation of therapy and safety assessments. Results The median time to recurrence of P aeruginosa (any strain) was similar between the two groups. In total, 93% and 92% of the patients were free of P aeruginosa infection 1 month after the end of treatment and 66% and 69% remained free at the final visit in the 28-day and 56-day groups, respectively. TIS was well tolerated. Conclusions Treatment with TIS for 28 days is an effective and well tolerated therapy for early P aeruginosa infection in patients with CF. Trial registration number NCT00391976.

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.

Antibiotic resistance (ABR) is a global public health threat. Despite the emergence of highly resistant organisms and the huge medical need for new drugs, the development of antibacterials has slowed to an unacceptable level worldwide. Numerous government and non-government agencies have called for public-private partnerships and innovative funding mechanisms to address this problem. To respond to this public health crisis, the Innovative Medicines Initiative Joint Undertaking programme has invested more than €660 million, with a goal of matched contributions from the European Commission and the European Federation of Pharmaceutical Industries and Associations, in the development of new antibacterial strategies. The New Drugs for Bad Bugs (ND4BB) programme, an Innovative Medicines Initiative, has the ultimate goal to boost the fight against ABR at every level from basic science and drug discovery, through clinical development to new business models and responsible use of antibiotics. Seven projects have been launched within the ND4BB programme to achieve this goal. Four of them will include clinical trials of new anti-infective compounds, as well as epidemiological studies on an unprecedented scale, which will increase our knowledge of ABR and specific pathogens, and improve the designs of the clinical trials with new investigational drugs. The need for rapid concerted action has driven the funding of seven topics, each of which should add significantly to progress in the fight against ABR. ND4BB unites expertise and provides a platform where the commitment and resources required by all parties are streamlined into a joint public-private partnership initiative of unprecedented scale.

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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.

Background Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6–21 years. Methods CF patients with a forced expiratory volume in 1 second (FEV1) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial. Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug). The primary endpoint was relative change in forced expiratory volume in 1 second (FEV1) % predicted from baseline to Day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV1 % predicted. Other endpoints included Pa sputum density and safety. Results A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV1 59.2% predicted, Pa sputum density 7.4 log10 colony forming units [CFU]) per gram were randomized. Mean treatment differences (TIP–placebo) were 5.9% (p=0.148) and 4.4% (p<0.05) for relative and absolute change in FEV1 % predicted respectively. TIP significantly reduced Pa sputum density by –1.2 log10 CFU (p=0.002). Treatment with TIP was well tolerated. Conclusions Relative change in FEV1 % predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naïve patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV1 % predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients.

Cystic fibrosis (CF) is a lethal, monogenic disorder that affects multiple organ systems of the body.