Pitavastatin-Incorporated Nanoparticles for Chronic Limb Threatening Ischemia: A Phase I/IIa Clinical Trial
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- Matsumoto Takuya
- Department of Vascular Surgery, National Hospital Organization Fukuoka-higashi Medical Center Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Yoshino Shinichiro
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Furuyama Tadashi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Morisaki Koichi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Nakano Kaku
- Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University
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- Koga Jun-ichiro
- Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University Department of Cardiovascular Medicine, Kyusyu University Graduate School of Medical Sciences
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- Maehara Yoshihiko
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Komori Kimihiro
- Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine
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- Mori Masaki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
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- Egashira Kensuke
- Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University Department of Translational Medicine, Kyushu University Graduate School of Pharmaceutical Sciences
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Description
<p>Aim: To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI).</p><p>Methods: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n=4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period.</p><p>Results: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration–time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant.</p><p>Conclusions: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI. Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function.</p>
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 29 (5), 731-746, 2022-05-01
Japan Atherosclerosis Society
