Clinical trial NCT01315236
Conditions: Mycobacterium Infections, Nontuberculous
Keywords: Amikacin Liposome Inhalation Suspension (ALIS) Arikayce
Sponsor: Insmed Incorporated
Start date: 2012-04-19; Completion date: 2015-06-18
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy, safety and tolerability of 84 days of daily dosing of 590 mg of LAI versus placebo in patients with treatment refractory NTM lung disease.

The first part of the study is the 84-day double-blind phase to evaluate the primary and secondary endpoints.

Detailed description:
This was a Phase 2, randomized, double-blind study of efficacy, safety, and tolerability of once daily (QD) dosing of LAI 590 mg versus placebo for 84 days in subjects with treatment refractory NTM lung infection on a stable multidrug regimen. At the conclusion of the randomized double-blind phase of the study, subjects who consented to continue in the open-label phase of the study received LAI 590 mg QD for 84 additional days. All subjects were required to complete a 28-day safety follow-up after their end of treatment study visit (Day 168). Subjects completing this study were consented for enrollment in a long-term follow-up phase and were asked to return to the study site at 12 months and 24 months (per protocol Amendment #3, the 24-month follow-up visit was no longer required) (visit window ± 2 months) after the last dose of study drug (either after completing the randomized double-blind phase or the open-label phase). Subjects were stratified upon entering the study based on the presence or absence of cystic fibrosis (CF) and Mycobacterium avium complex versus M abscessus as the predominate NTM organism at baseline and were block randomized to receive either LAI or placebo in a 1:1 ratio in the double-blind phase.

Subjects completing the main study, and subjects who completed the 84-day open-label phase, were consented for enrollment in a post-LAI safety follow-up assessment and were asked to return to the study site 12 months (visit window ± 2 months) after the last dose of study drug (either after completing the randomized double-blind phase or the open-label phase). The screening period required obtaining 3 morning sputum specimens (spontaneous or induced) for mycobacteriology. At each post-screening sputum timepoint, at least 2 and preferably 3 sputum specimens were obtained. At Day 1 (baseline), subjects were evaluated pre-dose and post-dose at the study site. Subjects returned to the study site briefly on Day 2 for collection of serum samples to determine creatinine clearance. On Days 28, 56, and 84, study drug was administered at the site and the efficacy, safety, and tolerability of study drug were evaluated. At Day 85, those subjects continuing in the open-label phase of the study received LAI 590 mg at the study site with pre-dose and post-dose assessments for safety and efficacy. Subjects returned every 28 days (Days 112, 140, and 168) in the open-label phase. A 28-day, post-dose follow-up visit occurred at either Day 112 for those subjects who did not continue in the open-label phase or at Day 196 for those subjects who continued in the open-label phase.

Subjects completing the main study, and subjects who completed the 84-day open-label phase, were consented for enrollment in a post-LAI safety follow-up assessment and were asked to return to the study site 12 months (visit window ± 2 months) after the last dose of study drug (either after completing the randomized double-blind phase or the open-label phase). Arikace™, Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other studies evaluating amikacin liposome inhalation suspension.

Arms: arm 1: LAI 590 mg QD arm 2: placebo QD
Interventions: intervention 1: Liposomal amikacin for inhalation (LAI) intervention 2: placebo
Intervention descriptions: intervention 1: * Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
* 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
* Administration time is approximately 13 minutes.
* Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
* Subjects can continue with 84 additional days of dosing in the open label extension. intervention 2: * Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.
* Administration procedures, volume and administration time are similar to LAI.
* Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.

Protocol documents: