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A6280 - Safety and Tolerability of ARD-3150, Inhaled Liposomal Ciprofloxacin, in Patients with Bronchiectasis and Chronic Pseudomonas Aeruginosa Infection: Results from Two Phase 3 Trials
Author Block: S. Sethi1, C. Haworth2, A. M. Davis3, I. Gonda4, J. K. Froehlich4, A. E. O'Donnell5; 1University at Buffalo, State University of New York, Buffalo, NY, United States, 2Papworth Hospital, Cambridge, United Kingdom, 3Grifols, Inc, Research Triangle Park, NC, United States, 4Aradigm Corporation, Hayward, CA, United States, 5Georgetown Univ Hosp, Washington, DC, United States.
Rationale Non-cystic fibrosis bronchiectasis (NCFB) is a chronic lung disease characterized by recurrent infection and frequent exacerbations. ARD-3150, a once-daily inhaled antibiotic consisting of 135 mg/3 mL liposome-encapsulated and 54 mg/3 mL free ciprofloxacin was evaluated in 2 identical phase 3 trials in NCFB with chronic Pseudomonas aeruginosa (PA) lung infection. Pooled results from these trials, [ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245)], show significant reduction with ARD-3150 in frequency of pulmonary exacerbations (PEs). Here we report on their safety and tolerability results. Methods A total of 582 patients with ≥2 PEs treated with antibiotics in the preceding year were enrolled in ORBIT-3 and ORBIT-4. Nebulized ARD-3150 or placebo were administered once daily for six cycles of 28 days on and 28 days off treatment, for a total of 48 weeks. Physical examination, adverse events (AE), electrocardiogram, spirometry, laboratory tests and carbon monoxide diffusing capacity (DLCO) were collected at regular intervals. Results The safety population included patients who received at least one dose of study drug (ARD-3150, N=389 or placebo, N=193). AEs were reported for 88.2% and 94.3% of the ARD-3150- and placebo-treated patients, respectively. The majority of AEs were mild or moderate; severe AEs were reported for 21.9% of ARD-3150 patients and 24.4% of placebo patients. Patient discontinuations of study drug and study withdrawals due to an AE were 8.7% ARD-3150, 8.3% placebo and 5.4% ARD-3150, 3.6% placebo, respectively. SAEs were reported for 23.4% of ARD-3150 patients and 26.9% of placebo patients; the majority were not considered related to study drug (1.8% and 1.0% not related, respectively). Eleven deaths occurred during the trials (6 [1.5%] in the ARD-3150 group and 5 [2.6%] in the placebo group); none of the deaths were considered to be related to treatment. An equal percentage of patients (~35%) in each treatment group reported an AE that was considered related to study drug. A key AE of special interest, bronchospasm, was reported in 1.3% of ARD-3150 and 1.0% of placebo groups. There were no significant differences in pulmonary function and DLCO at week 48 between the pooled ARD-3150 and placebo groups. No clinically meaningful changes or differences between ARD-3150 and placebo were observed in the laboratory and electrocardiogram parameters. Conclusion ARD-3150 was well tolerated, with an AE profile similar to placebo in the 48-week trials. ARD-3150 inhalation did not produce throat or respiratory tract irritation or bronchospasm, a major concern with inhaled antibiotics in this population.