Tobramycin Inhalation Powder in Cystic Fibrosis Patients: Response by Age Group

Abstract

BACKGROUND: Tobramycin powder for inhalation (TIP) is a drug-device combination designed to reduce treatment time and improve ease of use compared with tobramycin inhalation solution (TIS) in cystic fibrosis (CF) patients. However, the ability of patients to use dry powder inhalers, and the efficacy of the treatments, may vary by age. METHODS: The "Establish a New Gold Standard for Efficacy and Safety With Tobramycin in Cystic Fibrosis" (EAGER) trial was a randomized, 24-week, multicenter, open-label, parallel-group study designed to evaluate the safety of TIP versus TIS in 553 subjects, ages > 6 years, with CF and P. aeruginosa infection. The main efficacy end point was percent-of-predicted FEV 1 at week 20 (end of third cycle of treatment). A post hoc analysis was undertaken in 517 subjects who took > 1 dose of study medication, to evaluate the relative efficacy and safety of TIP and TIS by age group: > 6 to < 13 y (children, n ‫؍‬ 46); > 13 to < 20 y (adolescents, n ‫؍‬ 114); and > 20 y (adults, n ‫؍‬ 357). RESULTS: Improvements in percent-of-predicted FEV 1 from baseline to end of cycle 3 were greatest in the children for both TIP and TIS. The treatment differences (TIP ؊ TIS) were 4.7% (85% CI ؊1.2 to 10.6), 3.7% (85% CI ؊0.1 to 7.5), and ؊0.8% (85% CI ؊3.1 to 1.5) in children, adolescents, and adults, respectively. Sputum P. aeruginosa density decreased from baseline with both treatments, with comparable treatment differences across the age groups after 3 cycles: children ؊0.93 (85% CI ؊2.4 to 0.5), adolescents ؊0.17 (85% CI ؊1.2 to 0.8), and adults ؊0.89 (85% CI ؊1.3 to ؊0.4). Overall, subject satisfaction scores were greater in all subjects with TIP, irrespective of age group. With the exception of cough and dysphonia, the safety profile of TIP was comparable to TIS, irrespective of age. CONCLUSIONS: TIP is comparable to TIS in efficacy outcomes and safety profile but had greater patient satisfaction in all the age groups.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

“…The dry powder formulation uses a T-326 inhaler, has shorter administration time and decreases the potential for contamination of the device but with increased side effects and tolerability issues [28]. This type of formulation may be preferred by patients because of the shorter administration duration compared to TSI [42]. With respect to pharmacokinetic properties, similar medication levels were observed with 112 mg of tobramycin powder every 12 h compared to 300 mg of TSI [43].…”

Recent advances in the management of cystic fibrosis

“…It was found to be comparable in terms of lung function changes and PA sputum density changes to the nebulised solution 19. It can be used by children aged 6 years and older but was associated with higher rates of cough and dysphonia than TIS.…”

Reply to the comment by Cipolla et al. on: Inhaled antimicrobial therapy—Barriers to effective treatment, by J. Weers, Adv. Drug Deliv. Rev. (2015), http://dx.doi.org/10.1016/j.addr.2014.08.013

“…For example, pediatric patients have a higher incidence of cough than do adult CF patients [7]. Nonetheless, TOBI Podhaler provides a valuable option for administration of aminoglycosides with a significantly lower burden of treatment.…”