Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection

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....

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Veröffentlicht in:	Thorax Jg. 68; H. 9; S. 818 - 825
Hauptverfasser:	Clancy, J P, Dupont, L, Konstan, M W, Billings, J, Fustik, S, Goss, C H, Lymp, J, Minic, P, Quittner, A L, Rubenstein, R C, Young, K R, Saiman, L, Burns, J L, Govan, J R W, Ramsey, B, Gupta, R
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England BMJ Publishing Group Ltd and British Thoracic Society 01.09.2013 BMJ Publishing Group LTD BMJ Publishing Group
Schriftenreihe:	Original article
Schlagworte:	Adolescent Adult Amikacin - administration & dosage Amikacin - adverse effects Analysis of Variance Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - adverse effects Antibiotics Bacterial Infection Child Cystic Fibrosis Cystic Fibrosis - complications Cystic Fibrosis - physiopathology Double-Blind Method Drug dosages FDA approval Female Forced Expiratory Volume Humans Infections Liposomes Male Microbial Sensitivity Tests Mortality Mutation Nebulizers and Vaporizers Patients Pharmacokinetics Pseudomonas aeruginosa Pseudomonas Infections - drug therapy Quality of Life Respiratory Infection Sputum - microbiology Young Adult United States > US Europe Cystic Fibrosis Bacterial Infection Respiratory Infection
ISSN:	0040-6376, 1468-3296, 1468-3296
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Zusammenfassung:	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.
Bibliographie:	href:thoraxjnl-68-818.pdf local:thoraxjnl;68/9/818 istex:D6E59547A98757F5A3D798E74EB2093A15AA6978 ArticleID:thoraxjnl-2012-202230 JPC and LD contributed equally. ark:/67375/NVC-Q73PX3TS-0 PMID:23749840 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 The Altera Nebulizer System is a registered trademark of PARI Respiratory Equipment (2943 Oak Lake Blvd, Midlothian, VA 23112, USA).
ISSN:	0040-6376 1468-3296 1468-3296
DOI:	10.1136/thoraxjnl-2012-202230