Conditions: Bronchiectasis
Keywords: Bronchiectasis Respiratory Infections Amikacin Respiratory Tract Diseases Respiratory Tract Infections Lung Diseases Pseudomonas aeruginosa Amikacin liposome inhalation suspension (ALIS)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 64
Healthy volunteers: no

Brief summary:
This is a study to determine the safety and tolerability of 28 days of daily dosing of two doses (280 mg and 560 mg) of Arikayce™ versus placebo in patients who have bronchiectasis and chronic infection due to Pseudomonas infection.

Detailed description:
Bronchiectasis is a chronic disorder of the major bronchi and bronchioles characterized by permanent dilation, microbial infection, a persistent inflammatory response with the release of immune mediators and microbial toxins leading to destruction. The origin of bronchiectasis varies, but the presence of microbial infection and a persistent inflammatory response is typical of the disease. The chronic nature of the infection and the associated considerable morbidity provides the rationale for using aerosolized antibiotics for the treatment of bronchiectasis patients.

This is a multi-national Phase 2 study of safety and tolerability of 28 days of daily dosing with two dose levels (280 mg and 560 mg) of Arikayce™ versus placebo in subjects with bronchiectasis and chronic Pseudomonas infection. Study subjects will be randomized to receive either study drug or placebo by inhalation via a PARI eFlow® nebulizer. Each subject will complete 28 days of daily dosing. All study subjects will be followed for microbiologic activity for 14 days after completion of treatment and for safety for 28 days post completion of study treatment.

The total study duration will be 56 days, with the screening visit occurring within the preceding 14 days prior to study day 1. At Day 1 (baseline), subjects will be evaluated at pre-dose and during the first 4-5 hours post-dose. Subjects will return at Week 2 (day 14) after start of treatment and at the end of Week 4 (Day 28) treatment period to determine safety and efficacy of Arikayce™. Subjects will be followed up on study Days 42 and 56 (about 2 and 4 weeks after end of treatment) for safety determination. After completion of this study, subjects will be followed up for an additional 6 months via phone contacts and records review, if hospitalized or treated for pulmonary exacerbation (under the extension protocol).

Clinical laboratory parameters, audiology testing, clinical adverse events and pulmonary function will be evaluated for all study subjects in order to determine the qualitative and quantitative safety and tolerability of Arikayce™ compared to placebo. Serum, urine and sputum specimens will be collected at periodic intervals to assess pharmacokinetics (PK) in subjects who consent for the PK portion of the study. Additionally, sputum samples will be collected to determine changes in bacterial density. Total Pulmonary Symptom Severity Score (PSSS) will be assessed, and respiratory quality of life will be evaluated by using the St. George's Respiratory Questionnaire (SGRQ). Arikace™,Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and the other studies evaluating amikacin liposome inhalation suspension.

Arms:
arm 1: Subjects in this arm of the cohort 1 will receive 280 mg of Arikayce™ arm 2: Subjects in this arm of the cohort 1 will receive matching placebo. arm 3: Subjects in this arm of the cohort 2 will receive 560 mg of Arikayce™ arm 4: Subjects in this arm of the cohort 2 will receive matching placebo

Interventions: intervention 1: 280 mg Arikayce™ intervention 2: Matching Placebo for Cohort 1 intervention 3: 560 mg Arikayce™ intervention 4: Matching Placebo for Cohort 2
Intervention descriptions: intervention 1: Study subjects will receive Arikace™ 280 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer. intervention 2: Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer. intervention 3: Study subjects will receive Arikace™ 560 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer. intervention 4: Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Protocol document: