Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase 1b/2a Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) In Cystic Fibrosis Patients With Chronic Infections Due To Pseudomonas Aeruginosa.|
- To evaluate the safety and tolerability of nebulized Arikace™. Safety will be evaluated by changes in FEV1, SaO2, chemistry and hematology lab tests, vital signs, and clinical exam, assess treatment-emergent AEs. [ Time Frame: 28 Days ]
- To assess pharmacokinetics (PK) of Arikace™ in serum [ Time Frame: 28 Days ]
- To assess pharmacokinetics (PK) of Arikace™ in urine [ Time Frame: 28 Days ]
- To evaluate sputum amikacin levels [ Time Frame: 28 Days ]
- To evaluate change in Pulmonary function [ Time Frame: 28 Days ]
- To evaluate change in density of Pseudomonas aeruginosa in sputum [ Time Frame: 28 Days ]
- To evaluate time to and duration of systemic antipseudomonal rescue therapy [ Time Frame: 28 Days ]
- To evaluate change in CFQ-R measurements [ Time Frame: 28 Days ]
|Study Start Date:||February 2007|
|Study Completion Date:||February 2010|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1 - 280 mg Arikayce
Subjects in this cohort will receive 280 mg of Arikayce
Placebo Comparator: Cohort 1 - Placebo
Subjects in this arm of cohort 1 will receive matching placebo
Experimental: Cohort 2 - 560 mg Arikayce
Subjects in this cohort will receive 560 mg of Arikayce
Placebo Comparator: Cohort 2 - Placebo
Subjects in this arm of cohort 2 will receive matching placebo
Cystic fibrosis (CF) is a genetic disease resulting from mutations in a 230 kb gene on chromosome 7 known as the cystic fibrosis transmembrane conductance regulator (CFTR). Study subjects with CF manifest pathological changes in a variety of organs that express CFTR. The lungs are frequently affected, the sequelae being chronic infections and airway inflammation. The principal goal of treatment of subjects with CF is to slow the chronic deterioration of lung function.
This is a Phase 2a study of safety, and tolerability of 28 days of daily dosing of two dose (280mg, and 560 mg) cohorts of Arikayce™ versus placebo. Study subjects will be randomized to receive either study drug or placebo (1.5% NaCl) by inhalation via a PARI eFlow nebulizer. Cohort 1 (280mg) will complete 28 days of daily dosing with Arikayce™ and 14 day post dosing safety evaluation by the Safety Committee (DSMB) before initiation of enrollment in Cohort 2 (560mg). Cohort 2 will complete 28 days of daily dosing, and a 14 day post dosing safety assessment by the DSMB to evaluate safety data. All study patients will be followed for safety, pharmacokinetics, clinical and microbiologic activity for 28 days post completion of study treatment.
The total study period will be up to 56 days, with screening visit occurring within the preceding 14 days prior to randomization. Patients will be clinically evaluated during the first 48 hours post-randomization, and weekly for the 28 days treatment period, and during the follow up visits at study days 35, 42, 49 and 56 days to determine safety, tolerability, pharmacokinetics (PK), and clinical, and microbiologic activity.
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 PK. Additionally; sputum samples will be collected to determine changes in bacterial density. Pulmonary function testing and CFQ-R measurements will be assessed at selected time points throughout the study.
DSMB has recommended the amendment of the main study to evaluate safety and efficacy of additional cycles of treatment with Arikayce™. All patients who were randomized in the main study, were compliant with the study protocol, and continue meeting study eligibility criteria can be consented to participate in the open-label extension to evaluate the safety, tolerability and efficacy of 560 mg once daily dose of Arikayce™ administered for six cycles over eighteen months. Each cycle will comprise of 28 days of treatment followed by 56 days off treatment. The total extension period will be up to 518 days (74 weeks, about 18 months).
Clinical laboratory parameters, audiology testing, clinical adverse events and pulmonary function will be evaluated for all study subjects in order to determine the longer term safety, tolerability, and efficacy of Arikayce™. Serum specimens will be collected at periodic intervals to assess PK for safety. Additionally, sputum samples will be collected to determine changes in bacterial density. Pulmonary function testing and CFQ-R measurements will be assessed at selected time points throughout the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00777296
|Macedonia, The Former Yugoslav Republic of|
|Skopje, Macedonia, The Former Yugoslav Republic of|
|Study Director:||Gina Eagle, MD||Insmed Incorporated|