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

J. P. Clancy, L. Dupont, M. W. Konstan, J. Billings, S. Fustik, C. H. Goss, J. Lymp, P. Minic, Alexandra Quittner, R. C. Rubenstein, K. R. Young, L. Saiman, J. L. Burns, J. R W Govan, B. Ramsey, R. Gupta

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)818-825
Number of pages8
JournalThorax
Volume68
Issue number9
DOIs
StatePublished - Sep 1 2013

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Pseudomonas Infections
Cystic Fibrosis
Pseudomonas aeruginosa
Placebos
Sputum
Safety
Lung
Quality of Life
Amikacin
Forced Expiratory Volume
Aerosols
Infection

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Clancy, J. P., Dupont, L., Konstan, M. W., Billings, J., Fustik, S., Goss, C. H., ... Gupta, R. (2013). Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax, 68(9), 818-825. https://doi.org/10.1136/thoraxjnl-2012-202230

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. / Clancy, J. P.; Dupont, L.; Konstan, M. W.; Billings, J.; Fustik, S.; Goss, C. H.; Lymp, J.; Minic, P.; Quittner, Alexandra; Rubenstein, R. C.; Young, K. R.; Saiman, L.; Burns, J. L.; Govan, J. R W; Ramsey, B.; Gupta, R.

In: Thorax, Vol. 68, No. 9, 01.09.2013, p. 818-825.

Research output: Contribution to journalArticle

Clancy, JP, Dupont, L, Konstan, MW, Billings, J, Fustik, S, Goss, CH, Lymp, J, Minic, P, Quittner, A, Rubenstein, RC, Young, KR, Saiman, L, Burns, JL, Govan, JRW, Ramsey, B & Gupta, R 2013, 'Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection', Thorax, vol. 68, no. 9, pp. 818-825. https://doi.org/10.1136/thoraxjnl-2012-202230
Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH et al. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013 Sep 1;68(9):818-825. https://doi.org/10.1136/thoraxjnl-2012-202230
Clancy, J. P. ; Dupont, L. ; Konstan, M. W. ; Billings, J. ; Fustik, S. ; Goss, C. H. ; Lymp, J. ; Minic, P. ; Quittner, Alexandra ; Rubenstein, R. C. ; Young, K. R. ; Saiman, L. ; Burns, J. L. ; Govan, J. R W ; Ramsey, B. ; Gupta, R. / Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. In: Thorax. 2013 ; Vol. 68, No. 9. pp. 818-825.
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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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AU - Clancy, J. P.

AU - Dupont, L.

AU - Konstan, M. W.

AU - Billings, J.

AU - Fustik, S.

AU - Goss, C. H.

AU - Lymp, J.

AU - Minic, P.

AU - Quittner, Alexandra

AU - Rubenstein, R. C.

AU - Young, K. R.

AU - Saiman, L.

AU - Burns, J. L.

AU - Govan, J. R W

AU - Ramsey, B.

AU - Gupta, R.

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N2 - 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.

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.

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