Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKACE™)

• Status: Completed
• Trial end date: 2008-02-27
• Target enrollment: 0
• Participant gender: All

Summary

A major factor in the respiratory health of cystic fibrosis (CF) subjects is acquisition of chronic Pseudomonas aeruginosa infections. The infection rate with P. aeruginosa increases with age and by age 18 years, 80% of CF subjects in the U.S. are infected. Liposomal Amikacin for Inhalation (Arikace™) is a sterile aqueous liposomal suspension consisting of amikacin sulfate encapsulated in liposomes. This formulation of amikacin maximizes the achievable dose and delivery to the lungs of subjects infected via a nebulizer. Because liposome particles are small enough to penetrate and diffuse through sputum into the bacterial biofilm, they deposit drug in close proximity to the bacterial colonies, thus improving the bioavailability of amikacin at the infection site. The clinically achievable doses of amikacin in the LAI formulation can effectively increase the half-life of the drug in the lungs, and decrease the potential for systemic toxicity. LAI offers several advantages over current therapies in treating CF subjects with chronic infection caused by P. aeruginosa.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Insmed Incorporated
• Treatments: Amikacin

Criteria

Inclusion Criteria:

• Written informed consent obtained from patient or designated legal guardian prior to the performance of any study related procedures.

• Male or female study subjects ≥6 years of age or older

• Confirmed diagnosis of CF

• History of chronic infection with P. aeruginosa

• Study subjects must produce a screening specimen that is positive for growth of P. aeruginosa

• FEV1 ≥ 40% predicted at Screening

• SaO2 ≥ 90% at Screening while breathing room air

• Ability to comply with study medication use, study visits and study procedures as judged by the investigator

• Ability to produce sputum or be willing to undergo an induction to produce sputum for clinical evaluation

• Clinically stable with no evidence of acute upper or lower respiratory tract infection of history of pulmonary exacerbation within 4 weeks prior to screening

Key Exclusion Criteria:

• Administration of any investigational drug within 8 weeks prior to Screening

• Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening

• History of alcohol, medication or illicit drug abuse within the 1 year prior to screening

• History of lung transplant

• Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)

• Positive pregnancy test

• Use of any anti-pseudomonal anitbiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones)within the 28 days prior to screening

• Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within 28 days prior to screening

• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening

• History of mycobacterial or Aspergillus infection

• Requiring treatment within 2 years prior to screening, and/or history of allergic bronchopulmonary aspergillosis.

• History of biliary cirrhosis with portal hypertension, or splenomegaly

• History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night Change in chest x-ray at screening (or within the 3 months prior to screening)