Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection
Identifieur interne : 000790 ( Istex/Corpus ); précédent : 000789; suivant : 000791Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection
Auteurs : J P Clancy ; L. Dupont ; M W Konstan ; J. Billings ; S. Fustik ; C H Goss ; J. Lymp ; P. Minic ; A L Quittner ; R C Rubenstein ; K R Young ; L. Saiman ; J L Burns ; J R W. Govan ; B. Ramsey ; R. Gupta ; J. Clancy ; R. Young ; R. Ahrens ; M. Aitken ; J. Billings ; A. Faro ; C. Goss ; D. Layish ; N. Lechtzin ; M. Light ; S. Miller ; S. Nasr ; J. Nick ; Rc Rubenstein ; A. Sannuti ; G. Sawicki ; J. Taylor-Cousar ; B. Trapnell ; J. Wallace ; P. Minic ; S. Fustik ; E. Solyom ; H. Mazurek ; Y. Antipkin ; A. Feketeova ; A. Senatorova ; E. Csiszer ; V. Kostromina ; B. Takac ; R. Ujhelyi ; A. Sovti ; Anne Marie Buccat ; Catherine DohertySource :
- Thorax [ 0040-6376 ] ; 2013-09.
Abstract
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.
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DOI: 10.1136/thoraxjnl-2012-202230
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><author><name sortKey="Clancy, J P" sort="Clancy, J P" uniqKey="Clancy J" first="J P" last="Clancy">J P Clancy</name><affiliation><mods:affiliation>Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Dupont, L" sort="Dupont, L" uniqKey="Dupont L" first="L" last="Dupont">L. Dupont</name><affiliation><mods:affiliation>Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Konstan, M W" sort="Konstan, M W" uniqKey="Konstan M" first="M W" last="Konstan">M W Konstan</name><affiliation><mods:affiliation>Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Billings, J" sort="Billings, J" uniqKey="Billings J" first="J" last="Billings">J. Billings</name><affiliation><mods:affiliation>Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Fustik, S" sort="Fustik, S" uniqKey="Fustik S" first="S" last="Fustik">S. Fustik</name><affiliation><mods:affiliation>Department of Pediatrics, University Clinical Centre, Skopje, Macedonia</mods:affiliation></affiliation></author><author><name sortKey="Goss, C H" sort="Goss, C H" uniqKey="Goss C" first="C H" last="Goss">C H Goss</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Lymp, J" sort="Lymp, J" uniqKey="Lymp J" first="J" last="Lymp">J. Lymp</name><affiliation><mods:affiliation>Seattle Children's Research Institute, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Minic, P" sort="Minic, P" uniqKey="Minic P" first="P" last="Minic">P. Minic</name><affiliation><mods:affiliation>Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia</mods:affiliation></affiliation></author><author><name sortKey="Quittner, A L" sort="Quittner, A L" uniqKey="Quittner A" first="A L" last="Quittner">A L Quittner</name><affiliation><mods:affiliation>Department of Psychology, University of Miami, Miami, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Rubenstein, R C" sort="Rubenstein, R C" uniqKey="Rubenstein R" first="R C" last="Rubenstein">R C Rubenstein</name><affiliation><mods:affiliation>Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Young, K R" sort="Young, K R" uniqKey="Young K" first="K R" last="Young">K R Young</name><affiliation><mods:affiliation>Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Saiman, L" sort="Saiman, L" uniqKey="Saiman L" first="L" last="Saiman">L. Saiman</name><affiliation><mods:affiliation>Department of Pediatrics, Columbia University, New York, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Burns, J L" sort="Burns, J L" uniqKey="Burns J" first="J L" last="Burns">J L Burns</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Govan, J R W" sort="Govan, J R W" uniqKey="Govan J" first="J R W" last="Govan">J R W. Govan</name><affiliation><mods:affiliation>Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK</mods:affiliation></affiliation></author><author><name sortKey="Ramsey, B" sort="Ramsey, B" uniqKey="Ramsey B" first="B" last="Ramsey">B. Ramsey</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Gupta, R" sort="Gupta, R" uniqKey="Gupta R" first="R" last="Gupta">R. Gupta</name><affiliation><mods:affiliation>Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA</mods:affiliation></affiliation></author><author wicri:is="80%"><name sortKey="Clancy, J" sort="Clancy, J" uniqKey="Clancy J" first="J" last="Clancy">J. Clancy</name></author><author wicri:is="80%"><name sortKey="Young, R" sort="Young, R" uniqKey="Young R" first="R" last="Young">R. Young</name></author><author wicri:is="80%"><name sortKey="Ahrens, R" sort="Ahrens, R" uniqKey="Ahrens R" first="R" last="Ahrens">R. Ahrens</name></author><author wicri:is="80%"><name sortKey="Aitken, M" sort="Aitken, M" uniqKey="Aitken M" first="M" last="Aitken">M. Aitken</name></author><author wicri:is="80%"><name sortKey="Billings, J" sort="Billings, J" uniqKey="Billings J" first="J" last="Billings">J. Billings</name></author><author wicri:is="80%"><name sortKey="Faro, A" sort="Faro, A" uniqKey="Faro A" first="A" last="Faro">A. Faro</name></author><author wicri:is="80%"><name sortKey="Goss, C" sort="Goss, C" uniqKey="Goss C" first="C" last="Goss">C. Goss</name></author><author wicri:is="80%"><name sortKey="Layish, D" sort="Layish, D" uniqKey="Layish D" first="D" last="Layish">D. Layish</name></author><author wicri:is="80%"><name sortKey="Lechtzin, N" sort="Lechtzin, N" uniqKey="Lechtzin N" first="N" last="Lechtzin">N. Lechtzin</name></author><author wicri:is="80%"><name sortKey="Light, M" sort="Light, M" uniqKey="Light M" first="M" last="Light">M. Light</name></author><author wicri:is="80%"><name sortKey="Miller, S" sort="Miller, S" uniqKey="Miller S" first="S" last="Miller">S. Miller</name></author><author wicri:is="80%"><name sortKey="Nasr, S" sort="Nasr, S" uniqKey="Nasr S" first="S" last="Nasr">S. Nasr</name></author><author wicri:is="80%"><name sortKey="Nick, J" sort="Nick, J" uniqKey="Nick J" first="J" last="Nick">J. Nick</name></author><author wicri:is="80%"><name sortKey="Rubenstein, Rc" sort="Rubenstein, Rc" uniqKey="Rubenstein R" first="Rc" last="Rubenstein">Rc Rubenstein</name></author><author wicri:is="80%"><name sortKey="Sannuti, A" sort="Sannuti, A" uniqKey="Sannuti A" first="A" last="Sannuti">A. Sannuti</name></author><author wicri:is="80%"><name sortKey="Sawicki, G" sort="Sawicki, G" uniqKey="Sawicki G" first="G" last="Sawicki">G. Sawicki</name></author><author wicri:is="80%"><name sortKey="Taylor Cousar, J" sort="Taylor Cousar, J" uniqKey="Taylor Cousar J" first="J" last="Taylor-Cousar">J. Taylor-Cousar</name></author><author wicri:is="80%"><name sortKey="Trapnell, B" sort="Trapnell, B" uniqKey="Trapnell B" first="B" last="Trapnell">B. Trapnell</name></author><author wicri:is="80%"><name sortKey="Wallace, J" sort="Wallace, J" uniqKey="Wallace J" first="J" last="Wallace">J. Wallace</name></author><author wicri:is="80%"><name sortKey="Minic, P" sort="Minic, P" uniqKey="Minic P" first="P" last="Minic">P. Minic</name></author><author wicri:is="80%"><name sortKey="Fustik, S" sort="Fustik, S" uniqKey="Fustik S" first="S" last="Fustik">S. Fustik</name></author><author wicri:is="80%"><name sortKey="Solyom, E" sort="Solyom, E" uniqKey="Solyom E" first="E" last="Solyom">E. Solyom</name></author><author wicri:is="80%"><name sortKey="Mazurek, H" sort="Mazurek, H" uniqKey="Mazurek H" first="H" last="Mazurek">H. Mazurek</name></author><author wicri:is="80%"><name sortKey="Antipkin, Y" sort="Antipkin, Y" uniqKey="Antipkin Y" first="Y" last="Antipkin">Y. Antipkin</name></author><author wicri:is="80%"><name sortKey="Feketeova, A" sort="Feketeova, A" uniqKey="Feketeova A" first="A" last="Feketeova">A. Feketeova</name></author><author wicri:is="80%"><name sortKey="Senatorova, A" sort="Senatorova, A" uniqKey="Senatorova A" first="A" last="Senatorova">A. Senatorova</name></author><author wicri:is="80%"><name sortKey="Csiszer, E" sort="Csiszer, E" uniqKey="Csiszer E" first="E" last="Csiszer">E. Csiszer</name></author><author wicri:is="80%"><name sortKey="Kostromina, V" sort="Kostromina, V" uniqKey="Kostromina V" first="V" last="Kostromina">V. Kostromina</name></author><author wicri:is="80%"><name sortKey="Takac, B" sort="Takac, B" uniqKey="Takac B" first="B" last="Takac">B. Takac</name></author><author wicri:is="80%"><name sortKey="Ujhelyi, R" sort="Ujhelyi, R" uniqKey="Ujhelyi R" first="R" last="Ujhelyi">R. Ujhelyi</name></author><author wicri:is="80%"><name sortKey="Sovti, A" sort="Sovti, A" uniqKey="Sovti A" first="A" last="Sovti">A. Sovti</name></author><author wicri:is="80%"><name sortKey="Buccat, Anne Marie" sort="Buccat, Anne Marie" uniqKey="Buccat A" first="Anne Marie" last="Buccat">Anne Marie Buccat</name></author><author wicri:is="80%"><name sortKey="Doherty, Catherine" sort="Doherty, Catherine" uniqKey="Doherty C" first="Catherine" last="Doherty">Catherine Doherty</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D6E59547A98757F5A3D798E74EB2093A15AA6978</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1136/thoraxjnl-2012-202230</idno><idno type="url">https://api.istex.fr/document/D6E59547A98757F5A3D798E74EB2093A15AA6978/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000790</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><author><name sortKey="Clancy, J P" sort="Clancy, J P" uniqKey="Clancy J" first="J P" last="Clancy">J P Clancy</name><affiliation><mods:affiliation>Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Dupont, L" sort="Dupont, L" uniqKey="Dupont L" first="L" last="Dupont">L. Dupont</name><affiliation><mods:affiliation>Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Konstan, M W" sort="Konstan, M W" uniqKey="Konstan M" first="M W" last="Konstan">M W Konstan</name><affiliation><mods:affiliation>Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Billings, J" sort="Billings, J" uniqKey="Billings J" first="J" last="Billings">J. Billings</name><affiliation><mods:affiliation>Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Fustik, S" sort="Fustik, S" uniqKey="Fustik S" first="S" last="Fustik">S. Fustik</name><affiliation><mods:affiliation>Department of Pediatrics, University Clinical Centre, Skopje, Macedonia</mods:affiliation></affiliation></author><author><name sortKey="Goss, C H" sort="Goss, C H" uniqKey="Goss C" first="C H" last="Goss">C H Goss</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Lymp, J" sort="Lymp, J" uniqKey="Lymp J" first="J" last="Lymp">J. Lymp</name><affiliation><mods:affiliation>Seattle Children's Research Institute, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Minic, P" sort="Minic, P" uniqKey="Minic P" first="P" last="Minic">P. Minic</name><affiliation><mods:affiliation>Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia</mods:affiliation></affiliation></author><author><name sortKey="Quittner, A L" sort="Quittner, A L" uniqKey="Quittner A" first="A L" last="Quittner">A L Quittner</name><affiliation><mods:affiliation>Department of Psychology, University of Miami, Miami, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Rubenstein, R C" sort="Rubenstein, R C" uniqKey="Rubenstein R" first="R C" last="Rubenstein">R C Rubenstein</name><affiliation><mods:affiliation>Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Young, K R" sort="Young, K R" uniqKey="Young K" first="K R" last="Young">K R Young</name><affiliation><mods:affiliation>Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Saiman, L" sort="Saiman, L" uniqKey="Saiman L" first="L" last="Saiman">L. Saiman</name><affiliation><mods:affiliation>Department of Pediatrics, Columbia University, New York, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Burns, J L" sort="Burns, J L" uniqKey="Burns J" first="J L" last="Burns">J L Burns</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Govan, J R W" sort="Govan, J R W" uniqKey="Govan J" first="J R W" last="Govan">J R W. Govan</name><affiliation><mods:affiliation>Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK</mods:affiliation></affiliation></author><author><name sortKey="Ramsey, B" sort="Ramsey, B" uniqKey="Ramsey B" first="B" last="Ramsey">B. Ramsey</name><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Gupta, R" sort="Gupta, R" uniqKey="Gupta R" first="R" last="Gupta">R. Gupta</name><affiliation><mods:affiliation>Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA</mods:affiliation></affiliation></author><author wicri:is="80%"><name sortKey="Clancy, J" sort="Clancy, J" uniqKey="Clancy J" first="J" last="Clancy">J. Clancy</name></author><author wicri:is="80%"><name sortKey="Young, R" sort="Young, R" uniqKey="Young R" first="R" last="Young">R. Young</name></author><author wicri:is="80%"><name sortKey="Ahrens, R" sort="Ahrens, R" uniqKey="Ahrens R" first="R" last="Ahrens">R. Ahrens</name></author><author wicri:is="80%"><name sortKey="Aitken, M" sort="Aitken, M" uniqKey="Aitken M" first="M" last="Aitken">M. Aitken</name></author><author wicri:is="80%"><name sortKey="Billings, J" sort="Billings, J" uniqKey="Billings J" first="J" last="Billings">J. Billings</name></author><author wicri:is="80%"><name sortKey="Faro, A" sort="Faro, A" uniqKey="Faro A" first="A" last="Faro">A. Faro</name></author><author wicri:is="80%"><name sortKey="Goss, C" sort="Goss, C" uniqKey="Goss C" first="C" last="Goss">C. Goss</name></author><author wicri:is="80%"><name sortKey="Layish, D" sort="Layish, D" uniqKey="Layish D" first="D" last="Layish">D. Layish</name></author><author wicri:is="80%"><name sortKey="Lechtzin, N" sort="Lechtzin, N" uniqKey="Lechtzin N" first="N" last="Lechtzin">N. Lechtzin</name></author><author wicri:is="80%"><name sortKey="Light, M" sort="Light, M" uniqKey="Light M" first="M" last="Light">M. Light</name></author><author wicri:is="80%"><name sortKey="Miller, S" sort="Miller, S" uniqKey="Miller S" first="S" last="Miller">S. Miller</name></author><author wicri:is="80%"><name sortKey="Nasr, S" sort="Nasr, S" uniqKey="Nasr S" first="S" last="Nasr">S. Nasr</name></author><author wicri:is="80%"><name sortKey="Nick, J" sort="Nick, J" uniqKey="Nick J" first="J" last="Nick">J. Nick</name></author><author wicri:is="80%"><name sortKey="Rubenstein, Rc" sort="Rubenstein, Rc" uniqKey="Rubenstein R" first="Rc" last="Rubenstein">Rc Rubenstein</name></author><author wicri:is="80%"><name sortKey="Sannuti, A" sort="Sannuti, A" uniqKey="Sannuti A" first="A" last="Sannuti">A. Sannuti</name></author><author wicri:is="80%"><name sortKey="Sawicki, G" sort="Sawicki, G" uniqKey="Sawicki G" first="G" last="Sawicki">G. Sawicki</name></author><author wicri:is="80%"><name sortKey="Taylor Cousar, J" sort="Taylor Cousar, J" uniqKey="Taylor Cousar J" first="J" last="Taylor-Cousar">J. Taylor-Cousar</name></author><author wicri:is="80%"><name sortKey="Trapnell, B" sort="Trapnell, B" uniqKey="Trapnell B" first="B" last="Trapnell">B. Trapnell</name></author><author wicri:is="80%"><name sortKey="Wallace, J" sort="Wallace, J" uniqKey="Wallace J" first="J" last="Wallace">J. Wallace</name></author><author wicri:is="80%"><name sortKey="Minic, P" sort="Minic, P" uniqKey="Minic P" first="P" last="Minic">P. Minic</name></author><author wicri:is="80%"><name sortKey="Fustik, S" sort="Fustik, S" uniqKey="Fustik S" first="S" last="Fustik">S. Fustik</name></author><author wicri:is="80%"><name sortKey="Solyom, E" sort="Solyom, E" uniqKey="Solyom E" first="E" last="Solyom">E. Solyom</name></author><author wicri:is="80%"><name sortKey="Mazurek, H" sort="Mazurek, H" uniqKey="Mazurek H" first="H" last="Mazurek">H. Mazurek</name></author><author wicri:is="80%"><name sortKey="Antipkin, Y" sort="Antipkin, Y" uniqKey="Antipkin Y" first="Y" last="Antipkin">Y. Antipkin</name></author><author wicri:is="80%"><name sortKey="Feketeova, A" sort="Feketeova, A" uniqKey="Feketeova A" first="A" last="Feketeova">A. Feketeova</name></author><author wicri:is="80%"><name sortKey="Senatorova, A" sort="Senatorova, A" uniqKey="Senatorova A" first="A" last="Senatorova">A. Senatorova</name></author><author wicri:is="80%"><name sortKey="Csiszer, E" sort="Csiszer, E" uniqKey="Csiszer E" first="E" last="Csiszer">E. Csiszer</name></author><author wicri:is="80%"><name sortKey="Kostromina, V" sort="Kostromina, V" uniqKey="Kostromina V" first="V" last="Kostromina">V. Kostromina</name></author><author wicri:is="80%"><name sortKey="Takac, B" sort="Takac, B" uniqKey="Takac B" first="B" last="Takac">B. Takac</name></author><author wicri:is="80%"><name sortKey="Ujhelyi, R" sort="Ujhelyi, R" uniqKey="Ujhelyi R" first="R" last="Ujhelyi">R. Ujhelyi</name></author><author wicri:is="80%"><name sortKey="Sovti, A" sort="Sovti, A" uniqKey="Sovti A" first="A" last="Sovti">A. Sovti</name></author><author wicri:is="80%"><name sortKey="Buccat, Anne Marie" sort="Buccat, Anne Marie" uniqKey="Buccat A" first="Anne Marie" last="Buccat">Anne Marie Buccat</name></author><author wicri:is="80%"><name sortKey="Doherty, Catherine" sort="Doherty, Catherine" uniqKey="Doherty C" first="Catherine" last="Doherty">Catherine Doherty</name></author></analytic><monogr></monogr><series><title level="j">Thorax</title><title level="j" type="abbrev">Thorax</title><idno type="ISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><imprint><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><date type="published" when="2013-09">2013-09</date><biblScope unit="volume">68</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="818">818</biblScope></imprint><idno type="ISSN">0040-6376</idno></series><idno type="istex">D6E59547A98757F5A3D798E74EB2093A15AA6978</idno><idno type="DOI">10.1136/thoraxjnl-2012-202230</idno><idno type="href">thoraxjnl-68-818.pdf</idno><idno type="ArticleID">thoraxjnl-2012-202230</idno><idno type="PMID">23749840</idno><idno type="local">thoraxjnl;68/9/818</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0040-6376</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">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.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>J P Clancy</name><affiliations><json:string>Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</json:string></affiliations></json:item><json:item><name>L Dupont</name><affiliations><json:string>Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium</json:string></affiliations></json:item><json:item><name>M W Konstan</name><affiliations><json:string>Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA</json:string></affiliations></json:item><json:item><name>J Billings</name><affiliations><json:string>Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>S Fustik</name><affiliations><json:string>Department of Pediatrics, University Clinical Centre, Skopje, Macedonia</json:string></affiliations></json:item><json:item><name>C H Goss</name><affiliations><json:string>Department of Medicine, University of Washington, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>J Lymp</name><affiliations><json:string>Seattle Children's Research Institute, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>P Minic</name><affiliations><json:string>Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia</json:string></affiliations></json:item><json:item><name>A L Quittner</name><affiliations><json:string>Department of Psychology, University of Miami, Miami, Florida, USA</json:string></affiliations></json:item><json:item><name>R C Rubenstein</name><affiliations><json:string>Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</json:string></affiliations></json:item><json:item><name>K R Young</name><affiliations><json:string>Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA</json:string></affiliations></json:item><json:item><name>L Saiman</name><affiliations><json:string>Department of Pediatrics, Columbia University, New York, New York, USA</json:string></affiliations></json:item><json:item><name>J L Burns</name><affiliations><json:string>Department of Medicine, University of Washington, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>J R W Govan</name><affiliations><json:string>Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK</json:string></affiliations></json:item><json:item><name>B Ramsey</name><affiliations><json:string>Department of Medicine, University of Washington, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>R Gupta</name><affiliations><json:string>Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Open access</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Respiratory Infection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cystic Fibrosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Bacterial Infection</value></json:item></subject><articleId><json:string>thoraxjnl-2012-202230</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>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.</abstract><qualityIndicators><score>9.44</score><pdfVersion>1.6</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1702</abstractCharCount><pdfWordCount>5104</pdfWordCount><pdfCharCount>34068</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>245</abstractWordCount></qualityIndicators><title>Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><pmid><json:string>23749840</json:string></pmid><corporate><json:item><name>for the Arikace Study Group</name></json:item></corporate><genre><json:string>research-article</json:string></genre><host><volume>68</volume><publisherId><json:string>thorax</json:string></publisherId><pages><first>818</first></pages><issn><json:string>0040-6376</json:string></issn><issue>9</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-3296</json:string></eissn><title>Thorax</title></host><author_non-byline><json:item><name>J Clancy</name></json:item><json:item><name>R Young</name></json:item><json:item><name>R Ahrens</name></json:item><json:item><name>M Aitken</name></json:item><json:item><name>J Billings</name></json:item><json:item><name>A Faro</name></json:item><json:item><name>C Goss</name></json:item><json:item><name>D Layish</name></json:item><json:item><name>N Lechtzin</name></json:item><json:item><name>M Light</name></json:item><json:item><name>S Miller</name></json:item><json:item><name>S Nasr</name></json:item><json:item><name>J Nick</name></json:item><json:item><name>RC Rubenstein</name></json:item><json:item><name>A Sannuti</name></json:item><json:item><name>G Sawicki</name></json:item><json:item><name>J Taylor-Cousar</name></json:item><json:item><name>B Trapnell</name></json:item><json:item><name>J Wallace</name></json:item><json:item><name>P Minic</name></json:item><json:item><name>S Fustik</name></json:item><json:item><name>E Solyom</name></json:item><json:item><name>H Mazurek</name></json:item><json:item><name>Y Antipkin</name></json:item><json:item><name>A Feketeova</name></json:item><json:item><name>A Senatorova</name></json:item><json:item><name>E Csiszer</name></json:item><json:item><name>V Kostromina</name></json:item><json:item><name>B Takac</name></json:item><json:item><name>R Ujhelyi</name></json:item><json:item><name>A Sovtić</name></json:item><json:item><name>Anne Marie Buccat</name></json:item><json:item><name>Catherine Doherty</name></json:item></author_non-byline><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1136/thoraxjnl-2012-202230</json:string></doi><id>D6E59547A98757F5A3D798E74EB2093A15AA6978</id><score>0.28290954</score><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/D6E59547A98757F5A3D798E74EB2093A15AA6978/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/D6E59547A98757F5A3D798E74EB2093A15AA6978/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/D6E59547A98757F5A3D798E74EB2093A15AA6978/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><availability status="free"><p>Open Access</p></availability><date>2013-06-08</date></publicationStmt><notesStmt><note>JPC and LD contributed equally.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><author><orgName>for the Arikace Study Group</orgName></author><author xml:id="author-2"><persName><forename type="first">J P</forename><surname>Clancy</surname></persName><affiliation>Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation></author><author xml:id="author-3"><persName><forename type="first">L</forename><surname>Dupont</surname></persName><affiliation>Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium</affiliation></author><author xml:id="author-4"><persName><forename type="first">M W</forename><surname>Konstan</surname></persName><affiliation>Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA</affiliation></author><author xml:id="author-5"><persName><forename type="first">J</forename><surname>Billings</surname></persName><affiliation>Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author xml:id="author-6"><persName><forename type="first">S</forename><surname>Fustik</surname></persName><affiliation>Department of Pediatrics, University Clinical Centre, Skopje, Macedonia</affiliation></author><author xml:id="author-7"><persName><forename type="first">C H</forename><surname>Goss</surname></persName><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation></author><author xml:id="author-8"><persName><forename type="first">J</forename><surname>Lymp</surname></persName><affiliation>Seattle Children's Research Institute, Seattle, Washington, USA</affiliation></author><author xml:id="author-9"><persName><forename type="first">P</forename><surname>Minic</surname></persName><affiliation>Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia</affiliation></author><author xml:id="author-10"><persName><forename type="first">A L</forename><surname>Quittner</surname></persName><affiliation>Department of Psychology, University of Miami, Miami, Florida, USA</affiliation></author><author xml:id="author-11"><persName><forename type="first">R C</forename><surname>Rubenstein</surname></persName><affiliation>Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</affiliation></author><author xml:id="author-12"><persName><forename type="first">K R</forename><surname>Young</surname></persName><affiliation>Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA</affiliation></author><author xml:id="author-13"><persName><forename type="first">L</forename><surname>Saiman</surname></persName><affiliation>Department of Pediatrics, Columbia University, New York, New York, USA</affiliation></author><author xml:id="author-14"><persName><forename type="first">J L</forename><surname>Burns</surname></persName><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation></author><author xml:id="author-15"><persName><forename type="first">J R W</forename><surname>Govan</surname></persName><affiliation>Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK</affiliation></author><author xml:id="author-16"><persName><forename type="first">B</forename><surname>Ramsey</surname></persName><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation></author><author xml:id="author-17"><persName><forename type="first">R</forename><surname>Gupta</surname></persName><affiliation>Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA</affiliation></author><author xml:id="author-18"><persName><forename type="first">J</forename><surname>Clancy</surname></persName></author><author xml:id="author-19"><persName><forename type="first">R</forename><surname>Young</surname></persName></author><author xml:id="author-20"><persName><forename type="first">R</forename><surname>Ahrens</surname></persName></author><author xml:id="author-21"><persName><forename type="first">M</forename><surname>Aitken</surname></persName></author><author xml:id="author-22"><persName><forename type="first">J</forename><surname>Billings</surname></persName></author><author xml:id="author-23"><persName><forename type="first">A</forename><surname>Faro</surname></persName></author><author xml:id="author-24"><persName><forename type="first">C</forename><surname>Goss</surname></persName></author><author xml:id="author-25"><persName><forename type="first">D</forename><surname>Layish</surname></persName></author><author xml:id="author-26"><persName><forename type="first">N</forename><surname>Lechtzin</surname></persName></author><author xml:id="author-27"><persName><forename type="first">M</forename><surname>Light</surname></persName></author><author xml:id="author-28"><persName><forename type="first">S</forename><surname>Miller</surname></persName></author><author xml:id="author-29"><persName><forename type="first">S</forename><surname>Nasr</surname></persName></author><author xml:id="author-30"><persName><forename type="first">J</forename><surname>Nick</surname></persName></author><author xml:id="author-31"><persName><forename type="first">RC</forename><surname>Rubenstein</surname></persName></author><author xml:id="author-32"><persName><forename type="first">A</forename><surname>Sannuti</surname></persName></author><author xml:id="author-33"><persName><forename type="first">G</forename><surname>Sawicki</surname></persName></author><author xml:id="author-34"><persName><forename type="first">J</forename><surname>Taylor-Cousar</surname></persName></author><author xml:id="author-35"><persName><forename type="first">B</forename><surname>Trapnell</surname></persName></author><author xml:id="author-36"><persName><forename type="first">J</forename><surname>Wallace</surname></persName></author><author xml:id="author-37"><persName><forename type="first">P</forename><surname>Minic</surname></persName></author><author xml:id="author-38"><persName><forename type="first">S</forename><surname>Fustik</surname></persName></author><author xml:id="author-39"><persName><forename type="first">E</forename><surname>Solyom</surname></persName></author><author xml:id="author-40"><persName><forename type="first">H</forename><surname>Mazurek</surname></persName></author><author xml:id="author-41"><persName><forename type="first">Y</forename><surname>Antipkin</surname></persName></author><author xml:id="author-42"><persName><forename type="first">A</forename><surname>Feketeova</surname></persName></author><author xml:id="author-43"><persName><forename type="first">A</forename><surname>Senatorova</surname></persName></author><author xml:id="author-44"><persName><forename type="first">E</forename><surname>Csiszer</surname></persName></author><author xml:id="author-45"><persName><forename type="first">V</forename><surname>Kostromina</surname></persName></author><author xml:id="author-46"><persName><forename type="first">B</forename><surname>Takac</surname></persName></author><author xml:id="author-47"><persName><forename type="first">R</forename><surname>Ujhelyi</surname></persName></author><author xml:id="author-48"><persName><forename type="first">A</forename><surname>Sovtić</surname></persName></author><author xml:id="author-49"><persName><forename type="first">Anne Marie</forename><surname>Buccat</surname></persName></author><author xml:id="author-50"><persName><forename type="first">Catherine</forename><surname>Doherty</surname></persName></author></analytic><monogr><title level="j">Thorax</title><title level="j" type="abbrev">Thorax</title><idno type="pISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><imprint><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><date type="published" when="2013-09"></date><biblScope unit="volume">68</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="818">818</biblScope></imprint></monogr><idno type="istex">D6E59547A98757F5A3D798E74EB2093A15AA6978</idno><idno type="DOI">10.1136/thoraxjnl-2012-202230</idno><idno type="href">thoraxjnl-68-818.pdf</idno><idno type="ArticleID">thoraxjnl-2012-202230</idno><idno type="PMID">23749840</idno><idno type="local">thoraxjnl;68/9/818</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2013-06-08</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>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.</p></abstract><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Open access</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>Respiratory Infection</term></item><item><term>Cystic Fibrosis</term></item><item><term>Bacterial Infection</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2013-06-08">Created</change><change when="2013-09">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/D6E59547A98757F5A3D798E74EB2093A15AA6978/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">thoraxjnl</journal-id><journal-id journal-id-type="nlm-ta">Thorax</journal-id><journal-id journal-id-type="publisher-id">thorax</journal-id><journal-title>Thorax</journal-title><abbrev-journal-title abbrev-type="publisher">Thorax</abbrev-journal-title><abbrev-journal-title>Thorax</abbrev-journal-title><issn pub-type="ppub">0040-6376</issn><issn pub-type="epub">1468-3296</issn><publisher><publisher-name>BMJ Publishing Group Ltd and British Thoracic Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">thoraxjnl-2012-202230</article-id><article-id pub-id-type="doi">10.1136/thoraxjnl-2012-202230</article-id><article-id pub-id-type="other">thoraxjnl;68/9/818</article-id><article-id pub-id-type="other">thoraxjnl;thoraxjnl-2012-202230</article-id><article-id pub-id-type="pmid">23749840</article-id><article-id pub-id-type="other">818</article-id><article-id pub-id-type="other">thoraxjnl-2012-202230</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cystic fibrosis</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Open access</subject></subj-group><series-title>Original article</series-title></article-categories><title-group><article-title>Phase II studies of nebulised Arikace in CF patients with <italic>Pseudomonas aeruginosa</italic> infection</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Clancy</surname><given-names>J P</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dupont</surname><given-names>L</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Konstan</surname><given-names>M W</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Billings</surname><given-names>J</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Fustik</surname><given-names>S</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Goss</surname><given-names>C H</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Lymp</surname><given-names>J</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Minic</surname><given-names>P</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Quittner</surname><given-names>A L</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author"><name><surname>Rubenstein</surname><given-names>R C</given-names></name><xref ref-type="aff" rid="af10">10</xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>K R</given-names></name><xref ref-type="aff" rid="af11">11</xref></contrib><contrib contrib-type="author"><name><surname>Saiman</surname><given-names>L</given-names></name><xref ref-type="aff" rid="af12">12</xref></contrib><contrib contrib-type="author"><name><surname>Burns</surname><given-names>J L</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Govan</surname><given-names>J R W</given-names></name><xref ref-type="aff" rid="af13">13</xref></contrib><contrib contrib-type="author"><name><surname>Ramsey</surname><given-names>B</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>R</given-names></name><xref ref-type="aff" rid="af14">14</xref></contrib><contrib contrib-type="author"><collab>for the Arikace Study Group</collab></contrib><contrib contrib-type="author non-byline"><name><surname>Clancy</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Young</surname><given-names>R</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Ahrens</surname><given-names>R</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Aitken</surname><given-names>M</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Billings</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Faro</surname><given-names>A</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Goss</surname><given-names>C</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Layish</surname><given-names>D</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Lechtzin</surname><given-names>N</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Light</surname><given-names>M</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Miller</surname><given-names>S</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Nasr</surname><given-names>S</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Nick</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Rubenstein</surname><given-names>RC</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Sannuti</surname><given-names>A</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Sawicki</surname><given-names>G</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Taylor-Cousar</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Trapnell</surname><given-names>B</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Wallace</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Minic</surname><given-names>P</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Fustik</surname><given-names>S</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Solyom</surname><given-names>E</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Mazurek</surname><given-names>H</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Antipkin</surname><given-names>Y</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Feketeova</surname><given-names>A</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Senatorova</surname><given-names>A</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Csiszer</surname><given-names>E</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Kostromina</surname><given-names>V</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Takac</surname><given-names>B</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Ujhelyi</surname><given-names>R</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Sovtić</surname><given-names>A</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Buccat</surname><given-names>Anne Marie</given-names></name></contrib><contrib contrib-type="author non-byline"><name><surname>Doherty</surname><given-names>Catherine</given-names></name></contrib></contrib-group><aff id="af1"><label>1</label><institution>Department of Pediatrics, Cincinnati Children's Hospital Medical Center</institution>, <addr-line>Cincinnati, Ohio</addr-line>, <country>USA</country></aff><aff id="af2"><label>2</label><institution>Department of Respiratory Medicine, Katholieke Universiteit Leuven</institution>, <addr-line>Leuven</addr-line>, <country>Belgium</country></aff><aff id="af3"><label>3</label><institution>Department of Pediatrics, Case Western Reserve University</institution>, <addr-line>Cleveland, Ohio</addr-line>, <country>USA</country></aff><aff id="af4"><label>4</label><addr-line>Pulmonary, Allergy and Critical Care Division</addr-line>, <institution>University of Minnesota</institution>, <addr-line>Minneapolis, Minnesota</addr-line>, <country>USA</country></aff><aff id="af5"><label>5</label><addr-line>Department of Pediatrics</addr-line>, <institution>University Clinical Centre</institution>, <addr-line>Skopje</addr-line>, <country>Macedonia</country></aff><aff id="af6"><label>6</label><addr-line>Department of Medicine</addr-line>, <institution>University of Washington</institution>, <addr-line>Seattle, Washington</addr-line>, <country>USA</country></aff><aff id="af7"><label>7</label><institution>Seattle Children's Research Institute</institution>, <addr-line>Seattle, Washington</addr-line>, <country>USA</country></aff><aff id="af8"><label>8</label><addr-line>Department of Pulmonology</addr-line>, <institution>Institute for Mother and Child Healthcare</institution>, <addr-line>Belgrade</addr-line>, <country>Serbia</country></aff><aff id="af9"><label>9</label><addr-line>Department of Psychology</addr-line>, <institution>University of Miami</institution>, <addr-line>Miami, Florida</addr-line>, <country>USA</country></aff><aff id="af10"><label>10</label><addr-line>Division of Pulmonary Medicine</addr-line>, <institution>The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania</institution>, <addr-line>Philadelphia, Pennsylvania</addr-line>, <country>USA</country></aff><aff id="af11"><label>11</label><institution>Department of Internal Medicine, Albert Einstein Medical Center</institution>, <addr-line>Philadelphia, Pennsylvania</addr-line>, <country>USA</country></aff><aff id="af12"><label>12</label><addr-line>Department of Pediatrics</addr-line>, <institution>Columbia University</institution>, <addr-line>New York, New York</addr-line>, <country>USA</country></aff><aff id="af13"><label>13</label><addr-line>Department of Medical Microbiology</addr-line>, <institution>University of Edinburgh</institution>, <addr-line>Edinburgh</addr-line>, <country>UK</country></aff><aff id="af14"><label>14</label><addr-line>Department of Development</addr-line>, <institution>Insmed Incorporated</institution>, <addr-line>Monmouth Junction, New Jersey</addr-line>, <country>USA</country></aff><author-notes><corresp><label>Correspondence to</label> Dr J P Clancy, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; <email>john.clancy@cchmc.org</email></corresp><fn><p>JPC and LD contributed equally.</p></fn><fn><p>The Altera Nebulizer System is a registered trademark of PARI Respiratory Equipment (2943 Oak Lake Blvd, Midlothian, VA 23112, USA).</p></fn></author-notes><pub-date pub-type="ppub"><month>9</month><year>2013</year></pub-date><pub-date pub-type="epub-original"><day>8</day><month>6</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>8</day><month>6</month><year>2013</year></pub-date><volume>68</volume><volume-id pub-id-type="other">68</volume-id><volume-id pub-id-type="other">68</volume-id><issue>9</issue><issue-id pub-id-type="other">thoraxjnl;68/9</issue-id><issue-id pub-id-type="other">9</issue-id><issue-id pub-id-type="other">68/9</issue-id><fpage>818</fpage><history><date date-type="received"><day>1</day><month>6</month><year>2012</year></date><date date-type="rev-recd"><day>25</day><month>4</month><year>2013</year></date><date date-type="accepted"><day>4</day><month>5</month><year>2013</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/"><p>This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link></p></license></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="thoraxjnl-68-818.pdf"></self-uri><abstract><sec><title>Rationale</title><p>Arikace is a liposomal amikacin preparation for aerosol delivery with potent <italic>Pseudomonas aeruginosa</italic> killing and prolonged lung deposition.</p></sec><sec><title>Objectives</title><p>To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with <italic>P aeruginosa</italic>.</p></sec><sec><title>Methods</title><p>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 (FEV<sub>1</sub>)), <italic>P aeruginosa</italic> density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire—Revised (CFQ-R).</p></sec><sec><title>Results</title><p>The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV<sub>1</sub> 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 <italic>P aeruginosa</italic> 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 FEV<sub>1</sub> 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 <italic>P aeruginosa</italic> density (n=49).</p></sec><sec><title>Conclusions</title><p>Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with <italic>P aeruginosa</italic> infection.</p></sec></abstract><kwd-group><kwd>Respiratory Infection</kwd><kwd>Cystic Fibrosis</kwd><kwd>Bacterial Infection</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><partName>Original article</partName></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection</title><partName>Original article</partName></titleInfo><name type="corporate"><namePart>for the Arikace Study Group</namePart></name><name type="personal"><namePart type="given">J P</namePart><namePart type="family">Clancy</namePart><affiliation>Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Dupont</namePart><affiliation>Department of Respiratory Medicine, Katholieke Universiteit Leuven, Leuven, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M W</namePart><namePart type="family">Konstan</namePart><affiliation>Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Billings</namePart><affiliation>Pulmonary, Allergy and Critical Care Division, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Fustik</namePart><affiliation>Department of Pediatrics, University Clinical Centre, Skopje, Macedonia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C H</namePart><namePart type="family">Goss</namePart><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Lymp</namePart><affiliation>Seattle Children's Research Institute, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Minic</namePart><affiliation>Department of Pulmonology, Institute for Mother and Child Healthcare, Belgrade, Serbia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A L</namePart><namePart type="family">Quittner</namePart><affiliation>Department of Psychology, University of Miami, Miami, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R C</namePart><namePart type="family">Rubenstein</namePart><affiliation>Division of Pulmonary Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K R</namePart><namePart type="family">Young</namePart><affiliation>Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Saiman</namePart><affiliation>Department of Pediatrics, Columbia University, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J L</namePart><namePart type="family">Burns</namePart><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J R W</namePart><namePart type="family">Govan</namePart><affiliation>Department of Medical Microbiology, University of Edinburgh, Edinburgh, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Ramsey</namePart><affiliation>Department of Medicine, University of Washington, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Gupta</namePart><affiliation>Department of Development, Insmed Incorporated, Monmouth Junction, New Jersey, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Clancy</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Young</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Ahrens</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Aitken</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Billings</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Faro</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Goss</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Layish</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">N</namePart><namePart type="family">Lechtzin</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Light</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Miller</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Nasr</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Nick</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">RC</namePart><namePart type="family">Rubenstein</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Sannuti</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">Sawicki</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Taylor-Cousar</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Trapnell</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Wallace</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Minic</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Fustik</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Solyom</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">H</namePart><namePart type="family">Mazurek</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">Y</namePart><namePart type="family">Antipkin</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Feketeova</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Senatorova</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Csiszer</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">V</namePart><namePart type="family">Kostromina</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Takac</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Ujhelyi</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Sovtić</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">Anne Marie</namePart><namePart type="family">Buccat</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><name type="personal"><namePart type="given">Catherine</namePart><namePart type="family">Doherty</namePart><role><roleTerm type="text">author non-byline</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><genre>hwp-journal-coll</genre><topic>Open access</topic></subject><originInfo><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><dateIssued encoding="w3cdtf">2013-09</dateIssued><dateCreated encoding="w3cdtf">2013-06-08</dateCreated><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>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.</abstract><note type="footnotes">JPC and LD contributed equally.</note><subject><genre>keywords</genre><topic>Respiratory Infection</topic><topic>Cystic Fibrosis</topic><topic>Bacterial Infection</topic></subject><relatedItem type="host"><titleInfo><title>Thorax</title></titleInfo><titleInfo type="abbreviated"><title>Thorax</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0040-6376</identifier><identifier type="eISSN">1468-3296</identifier><identifier type="PublisherID">thorax</identifier><identifier type="PublisherID-hwp">thoraxjnl</identifier><identifier type="PublisherID-nlm-ta">Thorax</identifier><part><date>2013</date><detail type="volume"><caption>vol.</caption><number>68</number></detail><detail type="issue"><caption>no.</caption><number>9</number></detail><extent unit="pages"><start>818</start></extent></part></relatedItem><identifier type="istex">D6E59547A98757F5A3D798E74EB2093A15AA6978</identifier><identifier type="DOI">10.1136/thoraxjnl-2012-202230</identifier><identifier type="href">thoraxjnl-68-818.pdf</identifier><identifier type="ArticleID">thoraxjnl-2012-202230</identifier><identifier type="PMID">23749840</identifier><identifier type="local">thoraxjnl;68/9/818</identifier><accessCondition type="use and reproduction" contentType="open-access">This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. 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|clé= ISTEX:D6E59547A98757F5A3D798E74EB2093A15AA6978
|texte= Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection
}}
| This area was generated with Dilib version V0.6.25. |  |