Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis
Diana Bilton, Tacjana Pressler, Isabelle Fajac, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L Quittner, Keith Liu, John P McGinnis 2nd, Gina Eagle, Renu Gupta, Michael W Konstan, CLEAR-108 Study Group, Sabine Renner, Christiane Knoop, Anne Malfroot, Lieven Dupont, Kristine Desager, Frans De Baets, Miroslava Bosheva, Vania Nedkova, Ivan Galabov, Ivanka Galeva, Andreas Freitag, Nancy Morrison, Pearce Wilcox, Tanja Pressler, Yves Martinet, Raphael Chiron, Isabelle Fajac, Stephan Dominique, Philippe Reix, Anne Prevotat, Isabelle Sermet, Isabelle Durieu, Rainald Fischer, Rudolf Huber, Doris Staab, Uwe Mellies, Wolfgang Sextro, Tobias Welte, Heinrike Wilkens, Urte Sommerwerk, Burkhard Bewig, Ilias Inglezos, Stavros-Eleftherios Doudounakis, Olga Bede, Ferenc Gönczi, Rita Újhelyi, Edward McKone, Paul McNally, Vincenzina Lucidi, Marco Cipolli, Mario La Rosa, Laura Minicucci, Rita Padoan, Giovanna Pisi, Rolando Gagliardini, Carla Colombo, Inez Bronsveld, Ewa Sapiejka, Henryk Mazurek, Dorota Sands, Grażyna Górnicka, Iwona Stelmach, Halina Batura-Gabryel, Marta Rachel, Predrag Minic, Jaroslava Orosova, Branko Takac, Anna Feketova, Carmen Martinez, Gloria Garcia Hernandez, Jose Ramon Villa-Asensi, Silvia Gartner, Amparo Sole, Anders Lindblad, Martin Ledson, Diana Bilton, Joanna Whitehouse, Alan Smyth, Ian Ketchell, Timothy Lee, Gordon MacGregor, Diana Bilton, Tacjana Pressler, Isabelle Fajac, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L Quittner, Keith Liu, John P McGinnis 2nd, Gina Eagle, Renu Gupta, Michael W Konstan, CLEAR-108 Study Group, Sabine Renner, Christiane Knoop, Anne Malfroot, Lieven Dupont, Kristine Desager, Frans De Baets, Miroslava Bosheva, Vania Nedkova, Ivan Galabov, Ivanka Galeva, Andreas Freitag, Nancy Morrison, Pearce Wilcox, Tanja Pressler, Yves Martinet, Raphael Chiron, Isabelle Fajac, Stephan Dominique, Philippe Reix, Anne Prevotat, Isabelle Sermet, Isabelle Durieu, Rainald Fischer, Rudolf Huber, Doris Staab, Uwe Mellies, Wolfgang Sextro, Tobias Welte, Heinrike Wilkens, Urte Sommerwerk, Burkhard Bewig, Ilias Inglezos, Stavros-Eleftherios Doudounakis, Olga Bede, Ferenc Gönczi, Rita Újhelyi, Edward McKone, Paul McNally, Vincenzina Lucidi, Marco Cipolli, Mario La Rosa, Laura Minicucci, Rita Padoan, Giovanna Pisi, Rolando Gagliardini, Carla Colombo, Inez Bronsveld, Ewa Sapiejka, Henryk Mazurek, Dorota Sands, Grażyna Górnicka, Iwona Stelmach, Halina Batura-Gabryel, Marta Rachel, Predrag Minic, Jaroslava Orosova, Branko Takac, Anna Feketova, Carmen Martinez, Gloria Garcia Hernandez, Jose Ramon Villa-Asensi, Silvia Gartner, Amparo Sole, Anders Lindblad, Martin Ledson, Diana Bilton, Joanna Whitehouse, Alan Smyth, Ian Ketchell, Timothy Lee, Gordon MacGregor
Abstract
Background: Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung.
Methods: Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R).
Results: The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, -4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF.
Conclusions: Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678.
Keywords: ALIS; Amikacin liposome inhalation suspension; CFQ-R; Cystic fibrosis; LAI; Liposomal amikacin for inhalation; Pseudomonas aeruginosa.
Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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Source: PubMed