PMID- 23749840
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20211021
IS  - 1468-3296 (Electronic)
IS  - 0040-6376 (Print)
IS  - 0040-6376 (Linking)
VI  - 68
IP  - 9
DP  - 2013 Sep
TI  - Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa 
      infection.
PG  - 818-25
LID - 10.1136/thoraxjnl-2012-202230 [doi]
AB  - RATIONALE: Arikace is a liposomal amikacin preparation for aerosol delivery with 
      potent Pseudomonas aeruginosa killing and prolonged lung deposition. OBJECTIVES: 
      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.
FAU - Clancy, J P
AU  - Clancy JP
AD  - Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio, USA. john.clancy@cchmc.org
FAU - Dupont, L
AU  - Dupont L
FAU - Konstan, M W
AU  - Konstan MW
FAU - Billings, J
AU  - Billings J
FAU - Fustik, S
AU  - Fustik S
FAU - Goss, C H
AU  - Goss CH
FAU - Lymp, J
AU  - Lymp J
FAU - Minic, P
AU  - Minic P
FAU - Quittner, A L
AU  - Quittner AL
FAU - Rubenstein, R C
AU  - Rubenstein RC
FAU - Young, K R
AU  - Young KR
FAU - Saiman, L
AU  - Saiman L
FAU - Burns, J L
AU  - Burns JL
FAU - Govan, J R W
AU  - Govan JR
FAU - Ramsey, B
AU  - Ramsey B
FAU - Gupta, R
AU  - Gupta R
CN  - Arikace Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00558844
SI  - ClinicalTrials.gov/NCT00777296
GR  - P30 DK089507/DK/NIDDK NIH HHS/United States
GR  - P30 DK027651/DK/NIDDK NIH HHS/United States
GR  - UL1 RR025014-03S5/RR/NCRR NIH HHS/United States
GR  - UL1 TR000003/TR/NCATS NIH HHS/United States
GR  - UL1TR000003/TR/NCATS NIH HHS/United States
GR  - UL1 RR025014/RR/NCRR NIH HHS/United States
GR  - UL1RR024134/RR/NCRR NIH HHS/United States
GR  - UL1 RR024134/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130608
PL  - England
TA  - Thorax
JT  - Thorax
JID - 0417353
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Liposomes)
RN  - 84319SGC3C (Amikacin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amikacin/*administration & dosage/*adverse effects
MH  - Analysis of Variance
MH  - Anti-Bacterial Agents/*administration & dosage/*adverse effects
MH  - Child
MH  - Cystic Fibrosis/complications/*physiopathology
MH  - Double-Blind Method
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Microbial Sensitivity Tests
MH  - Nebulizers and Vaporizers
MH  - Pseudomonas Infections/*drug therapy
MH  - *Pseudomonas aeruginosa
MH  - Quality of Life
MH  - Sputum/microbiology
MH  - Young Adult
PMC - PMC3756431
OTO - NOTNLM
OT  - Bacterial Infection
OT  - Cystic Fibrosis
OT  - Respiratory Infection
FIR - Clancy, J
IR  - Clancy J
FIR - Young, R
IR  - Young R
FIR - Ahrens, R
IR  - Ahrens R
FIR - Aitken, M
IR  - Aitken M
FIR - Billings, J
IR  - Billings J
FIR - Faro, A
IR  - Faro A
FIR - Goss, C
IR  - Goss C
FIR - Layish, D
IR  - Layish D
FIR - Lechtzin, N
IR  - Lechtzin N
FIR - Light, M
IR  - Light M
FIR - Miller, S
IR  - Miller S
FIR - Nasr, S
IR  - Nasr S
FIR - Nick, J
IR  - Nick J
FIR - Rubenstein, Rc
IR  - Rubenstein R
FIR - Sannuti, A
IR  - Sannuti A
FIR - Sawicki, G
IR  - Sawicki G
FIR - Taylor-Cousar, J
IR  - Taylor-Cousar J
FIR - Trapnell, B
IR  - Trapnell B
FIR - Wallace, J
IR  - Wallace J
FIR - Minic, P
IR  - Minic P
FIR - Fustik, S
IR  - Fustik S
FIR - Solyom, E
IR  - Solyom E
FIR - Mazurek, H
IR  - Mazurek H
FIR - Antipkin, Y
IR  - Antipkin Y
FIR - Feketeova, A
IR  - Feketeova A
FIR - Senatorova, A
IR  - Senatorova A
FIR - Csiszer, E
IR  - Csiszer E
FIR - Kostromina, V
IR  - Kostromina V
FIR - Takac, B
IR  - Takac B
FIR - Ujhelyi, R
IR  - Ujhelyi R
FIR - Sovtic, A
IR  - Sovtic A
FIR - Buccat, Anne Marie
IR  - Buccat AM
FIR - Doherty, Catherine
IR  - Doherty C
EDAT- 2013/06/12 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/06/11 06:00
PHST- 2013/06/11 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - thoraxjnl-2012-202230 [pii]
AID - 10.1136/thoraxjnl-2012-202230 [doi]
PST - ppublish
SO  - Thorax. 2013 Sep;68(9):818-25. doi: 10.1136/thoraxjnl-2012-202230. Epub 2013 Jun 
      8.