title: Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection.
abstract: BACKGROUND
  Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition.
  
  
  OBJECTIVE
  To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa.
  
  
  METHODS
  105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R).
  
  
  RESULTS
  The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs -0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49).
  
  
  CONCLUSIONS
  Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. john.clancy@cchmc.org
authors.forename: J P
authors.initials: JP
authors.lastname: Clancy
authors.forename: L
authors.initials: L
authors.lastname: Dupont
authors.forename: M W
authors.initials: MW
authors.lastname: Konstan
authors.forename: J
authors.initials: J
authors.lastname: Billings
authors.forename: S
authors.initials: S
authors.lastname: Fustik
authors.forename: C H
authors.initials: CH
authors.lastname: Goss
authors.forename: J
authors.initials: J
authors.lastname: Lymp
authors.forename: P
authors.initials: P
authors.lastname: Minic
authors.forename: A L
authors.initials: AL
authors.lastname: Quittner
authors.forename: R C
authors.initials: RC
authors.lastname: Rubenstein
authors.forename: K R
authors.initials: KR
authors.lastname: Young
authors.forename: L
authors.initials: L
authors.lastname: Saiman
authors.forename: J L
authors.initials: JL
authors.lastname: Burns
authors.forename: J R W
authors.initials: JR
authors.lastname: Govan
authors.forename: B
authors.initials: B
authors.lastname: Ramsey
authors.forename: R
authors.initials: R
authors.lastname: Gupta
mesh_terms: D000293:Adolescent; D000328:Adult; D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects*; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008081:Liposomes; D008297:Male; D008826:Microbial Sensitivity Tests; D009330:Nebulizers and Vaporizers; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D011788:Quality of Life; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D000583:Amikacin
keywords: Bacterial Infection; Cystic Fibrosis; Respiratory Infection