Ease of use of tobramycin inhalation powder compared with nebulized tobramycin and colistimethate sodium: a crossover study in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infection

Abstract

Background:This study assessed the ease of use of tobramycin inhalation powder (TIP) administered via T-326 inhaler versus tobramycin inhalation solution (TIS) and colistimethate sodium (COLI), both administered via nebulizers, for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF).Methods:A real-world, open-label, crossover, interventional phase IV study was conducted in CF patients aged ⩾6 years with forced expiratory volume in 1 second (FEV1) ⩾25% to ⩽90% predicted. Patients were assigned to one of the three treatment arms in Cycle 1; all patients received TIP in Cycle 2. Each cycle consisted of 28 days on and 28 days off the treatment.Results:A total of 60 patients [mean (standard deviation) age, 27.6 (8.4) years] were allocated to three treatment arms [TIS/TIP (n = 14); COLI/TIP (n = 28); TIP/TIP (n = 18)] in Cycle 1. The mean total administration time, which included device setup and cleaning, in Cycle 1 versus Cycle 2 for TIS/TIP, COLI/TIP, and TIP/TIP arms were 37.0 versus 5.0 min, 16.4 versus 3.8 min, and 4.2 versus 3.4 min, respectively. The difference in mean total administration time was significantly shorter in Cycle 2 than in Cycle 1 for TIS/TIP (p = 0.0112) and COLI/TIP (p = 0.0016) arms. Overall, 12 patients were found to have contaminated devices across the two treatment cycles. In the TIP/TIP arm, no contamination of the T-326 inhaler was observed in either cycle. Treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication and ACCEPT® questionnaire, was better overall for TIP compared with TIS and COLI. There were no unexpected adverse events and most were mild or moderate in intensity.Conclusion:The T-326 inhaler used to deliver TIP was easy to use, required shorter total administration time, and was much less frequently contaminated than the nebulizers. The safety findings observed for TIP were generally consistent with its established safety profile.

Cough as an adverse effect on inhalation pharmaceutical products

“…Furthermore, 92% of tobramycin inhalation powder subjects reported coughing prior to tobramycin inhalation powder administration, which implies that this adverse event might be disease or patient related. Other studies have also reported coughing as a common adverse event after tobramycin inhalation solution treatment in cystic fibrosis (Greenwood et al, 2017; Hubert et al, 2009; Lenney et al, 2011; Mazurek et al, 2014) and bronchiectasis (Barker et al, 2000; Scheinberg & Shore, 2005) patients. Nebulised colistimethate sodium also caused coughing in a small proportion of cystic fibrosis subjects (Greenwood et al, 2017).…”

“…Other studies have also reported coughing as a common adverse event after tobramycin inhalation solution treatment in cystic fibrosis (Greenwood et al, 2017; Hubert et al, 2009; Lenney et al, 2011; Mazurek et al, 2014) and bronchiectasis (Barker et al, 2000; Scheinberg & Shore, 2005) patients. Nebulised colistimethate sodium also caused coughing in a small proportion of cystic fibrosis subjects (Greenwood et al, 2017). Although tobramycin inhalation powder induced coughs, the post‐inhalation cough rates reduces over time with repeated dosing, probably due to acclimatisation of the airways and cough receptors.…”

“…Most of the studies (Barker et al, 2000; Greenwood et al, 2017; Konstan, Flume, et al, 2011; Lenney et al, 2011; Mazurek et al, 2014) on inhaled tobramycin mentioned above used the sulfate salt. Interestingly, inhaled tobramycin free base showed a low incidence of cough.…”

Tobramycin inhalation powder for the treatment of pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis: a review based on clinical evidence

“…Similarly, the 2403 study showed high scores for TSQM in cycle 1, which were either sustained or further improved in cycle 2 for the majority of domains, indicating greater treatment satisfaction in patients receiving TIP over TIS and COLI. 51 In the GB01 study, increases were seen in the scores for all four domains of TSQM (data on file).…”

“…Similar to the phase III study results, study 2403 showed that the T-326 Inhaler used to deliver TIP was easy to use and required shorter total administration time as compared with nebulizers used to deliver TIS or COLI ( Table 3 ). 43 , 51 The ETOILES study evaluated the safety profile of TIP and the BR01 study evaluated device contamination with nebulizers. In addition, three phase IV studies (2403, FREE, and GB01) evaluated patient-reported outcomes assessing patient satisfaction and adherence with TIP treatment.…”