Table 2.

Clinical trials of inhaled tobramycin in chronic Pseudomonas aeruginosa infection

		Drug			Clinical trial
		Study	Type	Patients and age	Treatment schedule	Results	Adverse events
TIS	TIS 300 mg/5 mg	Ramsey et al23 Quittner and Buu24	DB, PC, MC	N=520 >6 years with chronic infection	TIS BID Three cycles	FEV1 increase in TIS group. P. aeruginosa sputum density reduced in TIS group.	Tinnitus (P<0.03).
		Moss3	OL	N=128 Adolescents with chronic infection	TIS BID 12 cycles	FEV1 increase. Hospital admission and IV antibiotic courses were reduced. Weight gain.	Tinnitus. No significant changes in serum creatinine levels. No aminoglycoside-induced hearing loss.
		Murphy et al25	OL, PG, MC	N=181 6–10 years with chronic infection	TIS BID Seven cycles	No significant FEV1 improvement.	Hoarseness.
		Lenoir et al26	DB, PC, PG, MC	N=59 >6 years with chronic infection	TIS BID One cycle	FEV1 increase in TIS group.	No significant changes in serum creatinine levels. No hearing loss.
	TIS, 4 mg	Chuchalin et al27	DB, PC, PG, MC	N=247 >6 years with chronic infection	TIS BID Three cycles	FEV1 increase in TIS group.	No.
	TIS 5 mg versus TIS 4 mg	Mazurek et al28	OL, MC	N=321 >6 years with chronic infection	TIS 4 mg BID, one cycle (treatment arm) TIS 5 mg BID, one cycle (control arm)	FEV1 improvement in both groups (differences not significant).	No.
TIP		Konstan et al29 (EVOLVE)	Cycle 1:DB, PC, MC Cycle 2: OL, MC	N=9S	TIP BID Three cycles	FEV1 improvement since the end of the first cycle.	SAE more frequent in the placebo group (lung disorders).
		Konstan et al30 (EAGER)	OL, AC, MC	N=517	TIP BID (T-326) TIS 5 mg BID (Pari LC Plus®) Three cycles	FEV1 improvement similar in both groups.	More frequent in TIP group (differences not significant).
		Galeva et al31 Quittner et al32 (EDIT)	DB, PC	N=62 Naïve to inhaled antipseudomonal antibiotics	TIP BID, one cycle	FEV1 improvement in treatment group. P. aeruginosa sputum density reduced.	No.

Abbreviations: TIS, tobramycin inhaled solution; DB, double-blind; PC, placebo-controlled; MC, multicenter; N, number; BID, twice a day; FEV₁, forced expiratory volume in 1 second; P. aeruginosa, Pseudomonas aeruginosa; OL, open-label; IV, intravenous; PG, parallel-group; EVOLVE, Evaluate tobramycin inhaled dry powder efficacy trial; TIP, tobramycin inhaled powder; SAE, serious adverse events; EAGER, Establish a new gold standard efficacy and safety with tobramycin in cystic fibrosis trial; AC, active comparator; EDIT, Establish tobramycin dry powder efficacy in cystic fibrosis trial.