Amikacin Liposome Inhalation Suspension for Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial.

Patients with refractory complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population. Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT. Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed. In the ALIS-naive cohort, 83.3% of patients ( = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% ( = 32) had serious TEAEs; 26.7% ( = 24) achieved culture conversion by Month 6 and 33.3% ( = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients ( = 34/73) experienced respiratory TEAEs, and 27.4% ( = 20) had serious TEAEs; 9.6% ( = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% ( = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts. In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600).