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

Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, Lymp J, Minic P, Quittner AL, Rubenstein RC, Young KR, Saiman L, Burns JL, Govan JR, Ramsey B, Gupta R, Arikace Study Gro - Thorax (2013)

Bottom Line: Primary outcomes included safety and tolerability.Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021).Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. john.clancy@cchmc.org

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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Related in: MedlinePlus

Patient enrolment across the two Arikace studies. In the European study, 75 patients were screened, and 66 were randomised. In the US study, 56 patients were screened, and 46 were randomised. *Across all randomised subjects, seven subjects withdrew consent prior to dosing. Data shown is for the 105 subjects dosed at least once with Arikace or placebo.
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THORAXJNL2012202230F1: Patient enrolment across the two Arikace studies. In the European study, 75 patients were screened, and 66 were randomised. In the US study, 56 patients were screened, and 46 were randomised. *Across all randomised subjects, seven subjects withdrew consent prior to dosing. Data shown is for the 105 subjects dosed at least once with Arikace or placebo.

Mentions: A total of 105 CF subjects meeting enrolment criteria were screened, randomised and dosed in one of four Arikace dose groups or placebo (figure 1, and enrolment segregated by US and European sites: see online supplementary figure S1). Subjects (across both studies) were randomised to receive 70 mg (n=7), 140 mg (n=5), 280 mg (n=21), 560 mg (n=36), or placebo (n=36). Baseline demographic characteristics (all subjects) are provided in table 1 (and for each study: see online supplementary tables S1 and S2). Age, gender, body mass index (BMI), lung function (FEV1% predicted) and chronic TIS use were generally similar, but with milder disease in the 140 mg dose group (higher FEV1 and BMI, US study, n=5), and younger age in the 280 mg cohort (16 years, European study, n=21). Mucoid P aeruginosa infection rates were similar in the European and US studies (85% and 89%, respectively), while chronic TIS use was lower in the European versus US subjects (defined as >three 28-day cycles in the preceding 12 months, 19% and 35%, respectively). The European cohort was younger (median age of 16.5 years (±6 years, SD) compared with 30.5 years (±8 years, SD) for the US cohort), but with similar lung function (median FEV1% predicted, 65.7% (±20%) for Europe versus 65.3% (±19%) for USA).


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

Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, Lymp J, Minic P, Quittner AL, Rubenstein RC, Young KR, Saiman L, Burns JL, Govan JR, Ramsey B, Gupta R, Arikace Study Gro - Thorax (2013)

Patient enrolment across the two Arikace studies. In the European study, 75 patients were screened, and 66 were randomised. In the US study, 56 patients were screened, and 46 were randomised. *Across all randomised subjects, seven subjects withdrew consent prior to dosing. Data shown is for the 105 subjects dosed at least once with Arikace or placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756431&req=5

THORAXJNL2012202230F1: Patient enrolment across the two Arikace studies. In the European study, 75 patients were screened, and 66 were randomised. In the US study, 56 patients were screened, and 46 were randomised. *Across all randomised subjects, seven subjects withdrew consent prior to dosing. Data shown is for the 105 subjects dosed at least once with Arikace or placebo.
Mentions: A total of 105 CF subjects meeting enrolment criteria were screened, randomised and dosed in one of four Arikace dose groups or placebo (figure 1, and enrolment segregated by US and European sites: see online supplementary figure S1). Subjects (across both studies) were randomised to receive 70 mg (n=7), 140 mg (n=5), 280 mg (n=21), 560 mg (n=36), or placebo (n=36). Baseline demographic characteristics (all subjects) are provided in table 1 (and for each study: see online supplementary tables S1 and S2). Age, gender, body mass index (BMI), lung function (FEV1% predicted) and chronic TIS use were generally similar, but with milder disease in the 140 mg dose group (higher FEV1 and BMI, US study, n=5), and younger age in the 280 mg cohort (16 years, European study, n=21). Mucoid P aeruginosa infection rates were similar in the European and US studies (85% and 89%, respectively), while chronic TIS use was lower in the European versus US subjects (defined as >three 28-day cycles in the preceding 12 months, 19% and 35%, respectively). The European cohort was younger (median age of 16.5 years (±6 years, SD) compared with 30.5 years (±8 years, SD) for the US cohort), but with similar lung function (median FEV1% predicted, 65.7% (±20%) for Europe versus 65.3% (±19%) for USA).

Bottom Line: Primary outcomes included safety and tolerability.Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021).Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. john.clancy@cchmc.org

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.

Show MeSH
Related in: MedlinePlus