Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis Respiratory Infections Pulmonary Cystic Fibrosis cystic fibrosis transmembrane conductance regulator (CFTR) Anti-bacterial Agent Arikayce ALIS LAI
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 206
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the long term safety and tolerability of Liposomal Amikacin for Inhalation (LAI) 590 mg once daily (QD) in Cystic Fibrosis patients with chronic infection due to pseudomonas aeruginosa. This long-term, open-label, multi-cycle extension study enrolled subjects who had successfully completed study TR02-108, were compliant with the study protocol, and did not meet any of the listed study discontinuation criteria. The safety and tolerability of LAI were evaluated for up to approximately 2 years.

Detailed description:
This was a long-term, open-label, multi-cycle extension study for patients in the Phase 3 study TR02-108 and TR02-109 who had successfully completed the 168-day study period and met study safety criteria. As this was a safety and tolerability long-term extension study, no sample size calculations were performed. All patients who completed TR02-108, were compliant with the study protocol, and did not meet any of the criteria listed for study discontinuation (safety reasons or non-compliance) were able to participate in this open-label study.

The end of study visit for TR02-108 was to serve as the baseline study visit (Day 1) for TR02-110 if the patient had signed the informed consent at least 4 days prior to the end of study visit and met all safety criteria for TR02-110. If the end of study visit was not used as the baseline visit, a separate baseline visit (Day 1) was to be performed within 14 days of completing TR02-108.

Patients were to receive a delivered dose of 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles. The study was implemented as 2 consecutive extension periods, each consisting of 48 weeks (approximately 12 months). Patients were re-consented for the second extension period at the completion of the first extension period. The total study period was up to 96 weeks (approximately 2 years).

During the first 28 days of treatment, patients were evaluated at the study site bi-weekly for safety, tolerability and efficacy. Thereafter, for the duration of the study, patients were evaluated at the study site on the first and last days of dosing during the on-treatment periods. During the study, starting with the off-treatment period of Cycle 1, patients were contacted by telephone once during every 28-day period to assess safety. A final site visit occurred 28 days after last dose of LAI. 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: 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each).

Interventions: intervention 1: Liposomal amikacin for inhalation
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 in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.

Protocol document: